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Hormone-Dependent and Experience-Dependent Auditory Plasticity for Social Communication

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The auditory neural circuit is embedded in a physiological environment that can be influenced by hormones. Early work demonstrated that hormone mechanisms are highly responsive to social contexts. More recent work shows that hormones affect auditory processing across contexts, leading to adaptive responses to auditory cues, including those involved in social communication. This chapter addresses recent progress in studying these and related mechanisms among mammals in a maternal communication paradigm, wherein both reproductive hormones (e.g., estrogen, oxytocin) and social experience (infant–mother interaction) shape auditory responses to infant sounds. By broadly reviewing studies ranging from hormones and behavior to sensory processing and plasticity, this chapter lays out a systematic approach to investigating how hormones may provide a mechanism for enhancing the perception and learning of auditory cues in reproductive and other social contexts. As discussed, reproductive-related hormones may induce plasticity in central auditory circuitry to enable a sustained trace of infant vocalizations in the auditory cortex, allowing for better recognition and detection of infant cues and sustained maternal behavior.
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Hormone and Experience-Dependent Auditory Plasticity for Social Communication
Kelly K. Chong1
Robert C. Liu2
1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology
and Emory University, Atlanta, Georgia, 30332
Phone: 404-727-2990
Email: kchong31@gatech.edu
2Department of Biology, Emory University, Atlanta, Georgia, 30322
Phone: 404-727-5274l
Email: robert.liu@emory.edu
Keywords: motherhood, maternal behavior, parental behavior, communication, reproductive
hormone, estrogen, oxytocin, vocalization, ultrasonic vocalization, baby cry, social
neuroscience, auditory cortex, cortical plasticity, auditory plasticity, experience-dependent
plasticity
1. Introduction
Shortly after giving birth, primates quickly develop the ability to recognize the cries of
their own offspring, enabling them to identify their infants in a crowd (Jensen, 1965; Green &
Gustafson, 1983). The auditory sense is clearly an important way in which organisms perceive
and represent the world around them, and it often plays an essential role in communication
between individuals. How the auditory sense does so though is not just dependent on the
acoustics of the communicated sound itself. Instead, the context in which sounds are heard, as
well as the listener’s physiological state, can affect how the sound is perceived and made
meaningful. While many investigators in general seek to understand these influences on
audition, the role of one important determinant of an individual’s physiological state – hormones
– and its interactions with another – prior sensory experience – is often overlooked in studies of
the neural basis of audition.
This chapter selectively reviews recent progress in trying to understand auditory
processing and plasticity in more natural behavioral contexts wherein the physiological state of
an individual can be influenced by both hormones and sensory experience. “Context” is defined
here as external sources of stimuli in the environment aside from the communicated sound.
This might include other sounds or stimuli from other modalities, whether they originate from
other individuals in a social context or from abiotic sources of a nonsocial nature. “Physiological
state” generally refers to the internal form and function of an organism’s brain and body. Form
includes the neurochemical environment and anatomical structure, whereas function refers to
the mechanisms by which they act. An increasingly important class of neurochemicals to
understand are hormones, which are chemical messengers released into the circulation that
often exert their effects on a broad variety of cells that are distant from the source. This chapter
will describe examples of how contexts engage hormonal systems, focusing primarily on
auditory perception and learning in social contexts among mammals and especially rodents,
where recent studies are beginning to lay a framework for understanding the interplay of
hormones, experience, perception and learning.
Social context refers to interactions of one organism with one or more conspecifics.
Sounds perceived in a social context, such as vocalizations, play a communicative role, and
often drive neural activity in ways that are distinct from non-social contexts (Ehret, 2005;
Bennur et al., 2013). For example, in the mouse (Mus musculus), natural ultrasonic
vocalizations have been shown to be more intrinsically arousing than other types of non-vocal
ultrasounds, thereby engaging limbic areas differentially (Geissler et al., 2013). Work in
non-human primates has further shown that there is specialization in auditory processing areas
for vocalizations. Within anterior regions of the temporal lobe in rhesus macaques (Macaca
mulatta), neurons have been observed to be selectively responsive to conspecific vocalizations
rather than heterospecific vocalizations or sounds that are not vocalizations (Perrodin et al.,
2011). These "voice cells" were likened to "face cells" found in the fusiform gyrus, a visual
processing area. These examples highlight the importance of using vocalizations and studying
social contexts in order to better understand normal auditory processing, as has been
extensively done among nonmammalian vertebrates (also see Forlano et al., Chapter 2;
Wilczynski & Burmeister, Chapter 3; Caras & Remage-Healey, Chapter 4; Maney, Chapter 5).
Focusing on social context opens many opportunities to elucidate potential
hormone-experience dependent interactions in sensory processing and plasticity, as will be
detailed for one particular social context, the parent-offspring interaction during motherhood.
Motherhood has been associated with changes in auditory processing and learning of infant
sounds (Banerjee & Liu, 2013; Swain et al., 2014). In particular, mothers of many mammalian
species including Galapagos sea lions (Zalophus californianus wollebae) and Mexican
free-tailed bats (Tadarida brasiliensis mexicana), become attuned to the auditory cues of their
own offspring and can recognize and distinguish them from other infants (Trillmich, 1981;
Balcombe, 1990). This adaptive ability facilitates caregiving to offspring, increasing the survival
chance of subsequent generations. How such auditory abilities are acquired and maintained
are some of the key questions still to be elucidated. Hormones are likely to play a role in this
adaptation, given that reproductive hormones such as estrogen and oxytocin broadly regulate
maternal physiology of which auditory processing is but one component. In fact, as is discussed
in Section 2, there are many examples in which environmental contexts engage hormonal
systems in ways that affect sensory processing and plasticity.
2. Sensory Contexts and Hormones
To gain some insight into how experience and hormones may affect audition in a
maternal context, it is useful to examine previous studies that have investigated such
interactions in other sensory contexts. Examples of relevant hormones include glucocorticoids,
vasopressin, oxytocin, serotonin, norepinephrine, and estrogen; each can change dynamically
in social or non-social contexts, affect immediate sensory processing, or engage sensory
plasticity mechanisms.
2.1 Glucocorticoids
Glucocorticoids are a class of steroid hormone synthesized in the adrenal cortex, whose
release is governed by the activity of the hypothalamic-pituitary-adrenal (HPA) axis(Tsigos &
Chrousos, 2002). These hormones play important roles in metabolism and immune regulation,
and levels in the bloodstream respond dynamically to external cues(Chrousos, 1995).
Importantly, glucocorticoids also act in the brain, and can affect sensory processing under
various circumstances.
One circumstance is the light-dark cycle, which entrains many natural biological rhythms,
including glucocorticoids such as cortisol (Chung et al., 2011). Changes in glucocorticoid levels
are correlated with altered peripheral auditory reflexes during different times of the day
(Fehm-Wolfsdorf & Nagel, 1996), potentially by acting on glucocorticoid-sensitive neurons
along the auditory reflex pathway (ten Cate et al., 1993). The daily circadian cycle is also
associated with diurnal fluctuations in behavioral performance in sensory tasks. For example, in
humans, the ability to distinguish individual, rapid sound clicks reaches peak performance at
midnight compared to other times of the day (Lotze et al., 1999). In the freely moving rat,
(Rattus norvegicus) synaptic strengths in the visual cortex of have been shown to fluctuate in
concert with diurnal luminance levels, suggesting light-dark cycle can directly affect sensory
cortical neural activity (Tsanov & Manahan-Vaughan, 2007). Whether such behavioral and
neural changes with the light/dark context are directly caused by the changing glucocorticoid
levels or other circadian hormones has not yet been well elucidated, leaving open questions for
future investigation.
Exposure to predator cues provides a different context in which corticosterone has been
shown to increase in concentration within the brain (Apfelbach et al., 2005). Organisms need to
effectively sense predators to respond quickly, and adaptive responses can be facilitated by
enhancing how predator cues are processed. Auditory processing has been shown to change in
a predator avoidance context, where odors are often the key indicator of a predator’s presence.
In the mouse, fox urine odor (Vulpes vulpes) reduces the amplitude of N40 auditory
event-related potentials (Halene et al., 2009), possibly via a direct effect of higher circulating
corticosterone (Maxwell et al., 2006). Behavioral and amygdala neural responses to natural
vocalizations are also affected by the presence of a predator odor, with generally increased
amygdala activity and decreased approach behavior to vocalizations (Grimsley et al., 2013).
The enhanced amygdala activity observed may potentially be facilitated directly by the
expression of glucocorticoid receptors in the amygdala(Morimoto et al., 1996).
Outside of the predator context, exposure to stressful sounds has been found to
subsequently increase auditory sensitivity as well as the expression of glucocorticoid receptors
in auditory areas of the rat, such as the inferior colliculus (Mazurek et al., 2010). In addition,
increased stress levels have been shown to raise thresholds for the middle ear reflex in humans,
which is a reflex that functions to reduce the amount of force loud sounds inflict on the ear drum
to avoid damaging the cochlea (Fehm-Wolfsdorf et al., 1993). Delivery of exogenous cortisol,
the primary stress glucocorticoid, also raises this acoustic reflex threshold. In this case, higher
glucocorticoid levels result in sounds being experienced as subjectively louder by suppressing
the acoustic reflex. Taken together, these examples hint at a mechanism for the stressful
context of avoiding a predator to modulate glucocorticoid levels in a way that alters sensory
processing, though the direct links between endocrine release in this context and auditory
neural activity have still to be better established.
As these examples illustrate, glucocorticoid levels can be highly dependent upon and are
dynamically influenced by behavioral context. Moreover, within these contexts, studies suggest
alterations in sensory processing, often at early stages in the sensory pathway. While far from
definitive, these links help reinforce the hypothesis that hormones can dynamically modulate
sensory mechanisms, including audition, with context.
2.2 Vasopressin and Oxytocin
The above glucocorticoid examples emphasize the modulation of hormones in nonsocial
contexts. By contrast, vasopressin and oxytocin are neuropeptide hormones that are
specifically active in social contexts. Both are synthesized by the hypothalamus and stored in
the posterior pituitary gland for release(Brownstein et al., 1980). Vasopressin was originally
named for its function in constricting peripheral blood vessels, and has since been shown to
play an important role in social behavior(Meyer-Lindenberg et al., 2011). Vasopressin is
involved in the regulation of aggressive social behaviors in mammals (Goodson & Bass, 2001;
Semsar et al., 2001) as well as in social recognition (Tobin et al., 2010); (Wersinger et al., 2002).
Oxytocin was first discovered for its role in facilitating childbirth, with large surges in blood
concentrations of oxytocin coinciding with uterine contraction during labor. It has likewise since
been shown to be involved in the social context(Kirsch et al., 2005), and is implicated in social
pair bonding (Donaldson & Young, 2008), as well as social recognition in mammals (Ferguson
et al., 2001). To facilitate social interaction, the presence of vasopressin and oxytocin may alter
sensory processing (including auditory processing) in various social contexts including
aggression, conspecific recognition, and mating.
Vasopressin 1a and 1b receptors have been found to be expressed in auditory
processing areas of “singing mice” that use vocalizations for courtship (Campbell et al., 2009).
Moreover, systemic injections of vasopressin in rats have been shown to produce hearing
impairment, as measured by increased auditory brain stem thresholds (Naganuma et al., 2014).
While these results are suggestive, whether the effects of vasopressin on social recognition or
conspecific aggression in these cases are mediated by its direct actions on auditory neurons
remains to be explored (Bester-Meredith et al., 2015).
Oxytocin plays an important role in social bond formation, and it has been hypothesized
that it could do so by increasing the salience of conspecific cues(Burkett & Young, 2012). In a
genotyping study on humans, individuals with the presumably more efficient variant of the
oxytocin receptor had significantly higher self-reported hearing and understanding scores in
background noise (Tops et al., 2011). Early immunohistochemical work showed that oxytocin is
expressed in early auditory areas of the mustached bat (Pteronotus parnellii), including the
inferior colliculus and superior olivary complex (Kanwal & Rao, 2002), indicating that oxytocin
may potentially act directly on auditory brain areas. The auditory cortex also is significantly
activated in the lactating rat mother during pup suckling as assessed by fMRI, and oxytocin
receptor blockade through ICV administration of ornithine vasotocin significantly reduces
auditory cortical activity normally present during suckling(Febo et al., 2005). These studies hint
at a role for oxytocin in processing of social auditory stimuli.
In sum, both vasopressin and oxytocin play an important role in wide variety of social
contexts across species, and at least some of this function is attributable to direct actions of
these hormones on auditory circuits. Growing evidence further suggests oxytocin can even act
in sensory cortical areas to mediate plasticity, providing additional motivation to understand
mechanisms for direct hormone-experience interactions in social contexts (Marlin et al., 2015).
The potential influence of oxytocin in auditory mechanisms will be described in further detail in
section 3.5 in the context of maternal reproductive context.
2.3 Serotonin
Hormones such as oxytocin can act in sensory regions in ways that are reminiscent of
more traditional neurotransmitters. In fact, the line between neuro-active hormones and
neuromodulators is not clear-cut, as several neurochemicals can function as both. For example,
serotonin was initially described as a neurotransmitter(Twarog & Page, 1953), though it is
mostly synthesized in the body’s gastrointestinal tract by enterochromaffin cells to regulate
intestinal movements (Berger et al., 2009). It is transported through the bloodstream via
platelets(Lesch et al., 1993), and can act as a hormone on remote parts of the body. In the
brain, serotonin is mainly synthesized by the raphe nuclei of the brainstem. The serotonergic
system is responsive to chronically varying contexts, both non-social and social, which in turn
can lead to context-dependent sensory processing. One classic non-social example of
serotonin’s chronic responsiveness to sensory contexts is its sensitivity to seasonal changes in
the light/dark cycle (Lambert et al., 2002). In a social context, a study on electric fish
(Apteronotus leptorhynchus) showed that serotonin enhances perception of conspecific cues by
directly increasing burst spiking in electrosensory neurons, while simultaneously decreasing
aggressive behaviors (Deemyad et al., 2013).
Within mammalian auditory systems, serotonin receptor agonist administration in rats
has been shown to improve auditory filtering, where the amplitude of auditory evoked potentials
in response to closely paired clicks is reduced during the second click (Johnson et al., 1998). In
humans, serotonin reuptake inhibitor treatment has been shown to significantly improve clinical
measures of auditory processing in the elderly (Cruz et al., 2004). In mice, levels of serotonin in
the inferior colliculus along have been shown to respond dynamically with animal state (Hall et
al., 2010). Exposure to a conspecific stranger rapidly alters inferior collicular serotonin levels,
particularly during social interactions such as anogenital investigation (Hall et al., 2011; Hanson
& Hurley, 2014). There is even evidence for this state-dependent neurochemical to directly act
upon GABAergic neurons within the inferior colliculus, enhancing suppression of firing activity in
the auditory brainstem(Hurley & Sullivan, 2012). Serotonin can also modulate auditory cortical
plasticity within a fear conditioning context in adult big brown bats (Eptesicus fuscus), where
application of serotonin agonist or antagonist directly to auditory cortex can enhance or reverse
retuning of auditory cortical neurons’ best frequencies, respectively (Ji & Suga, 2007). Hence,
serotonin is an example of how a neuro-active hormone that responds to extrinsic contexts and
internal states can directly modulate auditory sensory processing and plasticity.
2.4 Norepinephrine
Norepinephrine is another neurochemical that has both traditional hormonal as well as
neuromodulatory functions. It is synthesized by the adrenal medulla, and released into the
blood as a hormone where it elicits sympathetic responses such as vasoconstriction and
increased heart rate (Euler & Liljestrand, 1946). Centrally, the locus coeruleus and the lateral
tegmental field are the main sources of norepinephrine within the brain, which can then affect
sensory processing across multiple modalities including olfaction, somatosensation, and
audition (Hurley et al., 2004). Norepinephrine has been strongly associated with heightened
states of arousal, during which learning of behaviorally important sensory cues can be
enhanced, thereby acting as a facilitator of plasticity (Harley, 1987; McGaugh, 2000).
In the auditory system, norepinephrine has been particularly well investigated for its
contributions to sensorineural plasticity both during development and adulthood. Critical periods
are windows of time during development when sensory systems more readily undergo plasticity.
A classic demonstration of the sensory critical period comes from the visual system, where
Hubel and Wiesel showed that ocular dominance columns dedicated to a specific eye in the
visual cortex would shrink if the eye was occluded during a critical window of development
(Wiesel & Hubel, 1963). Such experience-dependent plasticity has been shown to apply to
multiple sensory modalities, including the auditory system. Tonotopic map expansion in the
auditory cortex occurs when passive exposure of a developing animal to a pure tone expands
the amount of auditory cortical area dedicated to that frequency in adulthood. Norepinephrine
has recently been shown to be necessary for this type of passive exposure-driven,
critical-period tonotopic map expansion (Shepard et al., 2015a). Norepinephrine appears to
place the auditory cortex in a more “plastic” state that enables it to rewire itself based on the
stimuli it encounters. Norepinephrine has also been implicated in adult auditory cortical
plasticity. Pairing of stimulation of the locus coeruleus, the primary site of noradrenergic release
in the brain, with presentation of tones at a particular frequency, can result in a tuning shift
towards the paired tone frequency in both the auditory thalamus and cortex that then last for
many minutes (Edeline et al., 2011). Iontophoresis of norepinephrine directly into the auditory
cortex, when paired with tone presentation, also induces a shift of best frequency towards the
paired tone (Manunta & Edeline, 1997; Martins & Froemke, 2015). Interestingly, the locus
coeruleus itself will also become responsive to tones alone after the tone has been paired with
direct stimulation of the locus coeruleus (Martins & Froemke, 2015), hinting at a positive
feedback mechanism to robustly engage plasticity mechanisms for arousing sounds.
Thus, norepinephrine illustrates how hormones can change not only immediate sensory
processing due to arousal, but also how sensory processing proceeds in the future. Hormonal
effects on sensory learning may in fact provide an important means to modulate the strength of
memories in different contexts, including in the maternal context.
2.5 Estrogen
Estrogen adds to the argument that hormones can affect sensory perception and
learning in reproductive contexts. Estrogen is a steroid hormone that functions as the primary
female reproductive hormone, with the majority synthesized in the ovaries. Estrogens are also
present in the brain, and these are mostly aromatized from androgens within the brain (Wu et
al., 2009). Systemic estrogen levels in females naturally fluctuate with the menstrual or estrus
cycles, and as a steroid hormone, freely diffuses across cell membranes to affect estrogen
levels in the brain as well.
Estrogen receptors (ER) alpha and beta, which often have opposite effects on cellular
functions, are differentially expressed throughout the central nervous system, opening the
possibility that estrogens influence sensory processing through both direct and indirect modes
of action (also see Forlano et al., Chapter 2; Caras & Remage-Healey, Chapter 4; Maney,
Chapter 5). For example, both ER types are expressed along the auditory (Charitidi & Canlon,
2010) and visual (Ogueta et al., 1999; Munaut et al., 2001) pathways, including in cortical
regions (Kritzer, 2002). They are also found in many neuromodulatory nuclei that send diffuse
projections throughout the forebrain (Miranda & Liu, 2009), including into auditory areas.
Estrogens may therefore regulate neuromodulator systems that ultimately affect mood and
memory (Fink et al., 1996), in addition to modulating activity in auditory processing areas
(Charitidi et al., 2009).
Estrogens have been shown to influence both peripheral and central auditory function
(also see Forlano et al., Chapter 2; Wilczynski & Burmeister, Chapter 3; Caras &
Remage-Healey, Chapter 4; Maney, Chapter 5; Frisina & Frisina, Chapter 7). For example, in
northern leopard frogs (Lithobates pipiens), intraventricular injection of estrogen into females
can enhance evoked neural response in the auditory midbrain (Yovanof & Feng, 1983),
potentially through estrogen-concentrating cells in the preoptic area that project to the midbrain.
Indeed, frequency tuning and temporal responses of midbrain auditory neurons varies
seasonally to better transmit mating calls, an effect that is hypothesized to arise from seasonal
variation in reproductive hormone levels (Goense & Feng, 2005).
While these examples involve estrogen primarily acting indirectly on sensory systems,
there is also evidence that it can act directly on peripheral sensory neurons that process
conspecific cues in social contexts. For instance, the plainfin midshipman fish (Porichthys
notatus) displays seasonal fluctuations in reproductive hormone levels that facilitate breeding
during the summer months (Forlano et al., 2015) (Chapter 2) . Male midshipman fish produce a
hum advertisement call to attract mates, and endogenous or exogenously delivered estrogens
acting in the female’s peripheral hearing organ improves the temporal encoding of the call’s
harmonics by the peripheral afferents (Sisneros et al., 2004). This is thought to improve
detection and localization of mates.
Similarly, in the songbird, breeding levels of estrogen enhances a female’s behavioral
preference for the natural characteristics of male song (Searcy & Marler, 1981). This coincides
with an enhanced neural response to natural song, as measured by immediate early gene
induction in the female’s caudomedial nidopallium (NCM), a songbird analog of a higher-order
auditory cortical region (Maney et al., 2006) (Also see Maney, Chapter 5). At the
electrophysiological level, individual neurons in this same area (in males) show increased firing
and bursting to song playback after estradiol treatment (Remage-Healey et al., 2010),
presumably due to a large percentage of neurons in this region that express estrogen receptors
(Gahr, 2001) (also see Caras & Remage-Healey, Chapter 4). Finally, an indication that
estrogen not only modulates perception but also memory for song comes from a study that
inhibited local estrogen synthesis in NCM before and while animals listened to song (Yoder et
al., 2012). They found that the NCM electrophysiological response several hours later seemed
no longer to recognize familiar songs, in contrast to the normal functioning of NCM in control
animals. Taken together, these data provide some compelling evidence that estrogens can act
both directly and indirectly to affect the neural and behavioral response to conspecific stimuli in
social contexts, and motivates studying similar examples in mammalian sensory systems.
As the above cases illustrate, the hormonal state of an organism is often dynamically
affected by external context, with social contexts being particularly effective in modulating an
organism’s internal physiological state. Hormones can then act on sensory processing areas
both directly and indirectly to facilitate social responses to conspecific cues, not just by affecting
immediate perception, but also by modulating neural plasticity mechanisms that can change
how an organism processes those cues in the future. While suggestive, the listed examples
leave many gaps regarding the details of mechanisms by which hormones affect sensory
processing, motivating a more systematic approach that the maternal model will hopefully
provide. The examples that were covered were also mostly for subcortical regions, although
hormones and their receptors are also present in sensory cortical areas (Reul & de Kloet, 1985;
Kawata, 1995), presenting new opportunities for studying the role of hormones in higher-order
sensory processing.
3. Reproductive Model of Sensory Plasticity
External context and internal hormonal state clearly interact to influence sensory
processing and plasticity, particularly in support of social communication. However, a thorough
approach to elucidating such interactions at the level of single or multiple neuron activity has
been lagging, especially for higher-order aspects of auditory behavior like vocal discrimination
and categorization. Recent work on a maternal communication model therefore presents an
opportunity to more systematically explore how auditory neural activity and plasticity are
shaped by context and hormones.
During motherhood, hormonal fluctuations drive changes throughout the body and brain,
enabling the mother to better respond to and care for offspring. In many species, mothers
become more attuned to the sensory cues of infants. One of the best elucidated examples of
this comes from studies of lamb recognition by maternal ewes (Ovis aries) that learn to
selectively recognize their own kin rather than non-kin shortly after birth based on olfactory
(Poindron et al., 1980), and later auditory and visual (Keller et al., 2003) cues. Of particular
relevance for this chapter, auditory cues from infants provide a key stimulus to trigger maternal
behavior. For example, in humans, the sound of a baby cry elicits a so-called let-down reflex for
milk production in lactating mothers (McNeilly et al., 1983). This let-down reflex does not occur
before first pregnancy, indicating that the same sound comes to elicit different behavioral
responses before and after motherhood. How do reproductive-associated hormones and
maternal experience alter the neural circuitry that transforms sound input into such behavioral
responses? To elucidate this type of plasticity, several labs have begun exploring a maternal
mouse model of communication sound learning.
3.1 Maternal Mouse Communication Model
The mouse has become a good mammalian model to study the neurobiology of maternal
sensory processing involving auditory cues that acquire behavioral relevance. Mouse pups,
when separated from the nest, emit isolation calls, which are a class of ultrasonic vocalization
(USV) at frequencies greater than ~50kHz (Liu et al., 2003). Mouse mothers naturally and
reliably respond to pup isolation calls with phonotaxis, which involves approaching and
retrieving the pup back to the nest. On the other hand, female mice without any prior pup
exposure do not conduct sound-guided retrieval (Ehret & Haack, 1984). Such females though
can learn to retrieve pups when housed as a co-carer with a mother and her pups, and can
begin to display phonotaxis to pup call playback within five days after pup birth (Ehret, 1987).
Importantly, both mothers and recent co-carers will preferentially approach the sound of a pup
isolation call as opposed to a behaviorally neutral sound (Ehret et al., 1987; Lin et al., 2013),
demonstrating the efficacy of the vocalizations and not just other multimodal pup cues in
eliciting maternal behavior.
[PLACE FIGURE 1 NEAR HERE]
These data suggest that auditory cues from pups can be learned through the act of
caring for pups. However, the acquisition and maintenance of the auditory memory for these
sounds may differ for individuals depending on their physiological state when they learn the
calls’ behavioral relevance (Fig. 1). Interestingly, mothers retain pup call preference after
weaning (21 days after pup birth), whereas virgin co-carers with the same duration of care
experience apparently lose that preference post-weaning. This provides a hint that the
hormonal cocktail that motherhood entails (estrogen, progesterone, prolactin, oxytocin, etc.)
may modulate the auditory plasticity the brain undergoes during pup care experience (Lin et al.,
2013).
A first step in understanding such modulation is to uncover the exact form and function of
long-term neural changes in processing infant sounds. Much progress in the last several years
has led to a collection of findings that detail long-term changes in vocalization encoding mainly
at the level of the auditory cortex, where observed plasticity may support improvements in the
functional processing of pup vocalizations to generate appropriate maternal responses. These
studies have generally recorded electrophysiological responses from maternal animals with
varying levels of pup care experience and/or reproductive hormones, and compared them to
non-maternal animals, such as the pup-naïve virgins. Although correlational in nature, such
studies can reveal aspects of call-elicited auditory neural activity that are affected by
motherhood, laying a foundation for a deeper elucidation of the role that different reproductive
hormones play in shaping this activity.
3.2 Absence of Long-term Cortical Map Plasticity in the Maternal Model
The core auditory cortex, including the primary auditory cortex, represents the first stage
of cortical processing of sounds (Kaas & Hackett, 2000). A large literature beginning with
electroencephalography studies by Galambos and colleagues (Galambos, 1956) has
demonstrated that neural plasticity within primary auditory cortex provides a detectable trace of
a sound’s learned behavioral relevance (Weinberger, 2004; Shepard et al., 2012). These
studies have largely focused on making simple pure tones behaviorally relevant through
laboratory conditioning and training paradigms. This has generally revealed a retuning of the
excitatory receptive field of core auditory cortical neurons, leading to a topographical expansion
in the cortical area tuned to the newly relevant sound frequency (Recanzone et al., 1993).
Given this history of prior research, when considering the nature of auditory cortical
plasticity for infant cries, cortical map expansion becomes a natural phenomenon to investigate
as a trace of these calls’ acquired behavioral importance for mothers. However, the
manifestation of population-level frequency-tuning shifts for natural sounds may not be entirely
straightforward. Such sounds, including vocalizations, often have multiple harmonics, frequency
modulations, or acoustic features that overlap other sounds. This makes frequency map
expansion as the final, long-term trace of many different natural sounds’ behavioral relevance
potentially untenable within the finite cortical territory devoted to audition. The maternal mouse
paradigm presents an ideal model system in which to test whether frequency map expansion
occurs in natural, reproductive-related auditory learning contexts. Since pup USVs are
essentially single frequency whistles, but with natural variations in frequency, duration,
frequency modulation, and amplitude envelope (Liu et al., 2003; Liu et al., 2006), they provide
an intermediate level of acoustic complexity between the pure tones typically used in mapping
studies and the complex, multiharmonic vocalizations emitted by most species. Hence, if map
expansion were to normally occur in ethological learning paradigms, it would be expected to be
observable for maternal mice listening to pup USVs.
When this question was addressed though, a surprising result emerged. Mouse strains
typically feature an ultrasound field (UF) within the core auditory cortex that is specifically tuned
to pure tone frequencies above 50kHz (Stiebler et al., 1997). Would long-term map plasticity
emerge through the topographical expansion of the UF in maternal animals compared to
pup-naive female mice? Interestingly, unlike the laboratory conditioning paradigms in which
tones are paired with a reward or shock, no maternal expansion in the size of the UF itself was
in fact observed (Shepard et al., 2015b). There was also no expansion in the core auditory
cortical area responsive to natural pup USVs themselves, whether multiunit recording sites
were inside the UF or not. The lack of map expansion in this natural context does not imply that
such expansion cannot occur in other paradigms, such as developmental sound exposure (Han
et al., 2007; Shepard et al., 2015a). However, this result does suggest that in realistic learning
situations, auditory cortical map expansion per se need not be a long-term memory trace, even
if it might have a function during auditory learning itself (Reed et al., 2011). The conflicting data
on map expansion in a sound exposure/operant conditioning paradigm versus a maternal
paradigm may also be in part be due to the differences in what hormones are present during
these paradigms. During fear conditioning, unconditioned stimuli such as the foot shock will
increase plasma levels of corticosterone and norepinephrine release in the brain (Swenson &
Vogel, 1983; Galvez et al., 1996) in ways that are unlikely to be mirrored during infant-mother
interactions. The release of norepinephrine, as described in section 2.4, plays a crucial role in
critical period map plasticity of the auditory cortex, so its elevation during an adult fear
conditioning paradigm may also contribute to the map expansion seen that is lacking in the
social learning paradigm.
3.3 Long-term Excitatory Plasticity for Call Categorization and Discrimination
Even though map expansion is not the form that auditory cortical plasticity takes for the
long-term memory of infant cries, functionally relevant, long-term excitatory plasticity does
emerge in core auditory cortex in other ways. For example, in the first demonstration of coding
differences between maternal and non-maternal animals (Fig. 2), multiunit auditory cortical
responses in anesthetized mothers, but not pup-naïve virgins, were found to be robustly
entrained by the ~5 Hz temporal rhythm of natural bouts of pup USVs (Liu et al., 2006).
Moreover, the call-elicited firing rates of multiunits themselves, irrespective of how the units’
frequency tuning contributes to the tonotopic map, also appear to convey more information in
mothers than in virgins for detecting pup USVs and discriminating between them (Liu &
Schreiner, 2007).
[PLACE FIGURE 2 NEAR HERE]
While instructive, these early studies were conducted in anesthetized rather than awake
mice and focused on the somewhat coarse measure of multiunit activity. The responses of
different and diverse individual neurons are likely combined in multiunits or pools of single-units,
which may then obscure any systematic changes that could be present in one or another
specific neuronal cell type. To overcome this, it has become important to apply methods to
segregate the inherent diversity of cortical neurons (McCormick et al., 1985; Sugino et al.,
2006). In particular, a computational model of auditory sensitivity to a sound’s amplitude
envelope (Neubauer & Heil, 2008) can successfully carve out subsets of putative inhibitory
interneurons and pyramidal neurons in auditory cortex whose excitatory firing either faithfully
encode the acoustics of a sound’s onset, or not (Lin & Liu, 2010). In essence, these so-called
well- and poorly-predicted neurons, respectively, have feedforward response latencies to pup
USVs that either can or cannot be easily predicted from their pure tone responses.
Such a classification scheme has revealed a fairly specific form of excitatory plasticity for
pup USVs within a subset of putative pyramidal neurons in core auditory cortex, recorded from
passively listening, awake, head-fixed animals (Shepard et al., 2015b). This study focused on a
presumed function of vocalization encoding by investigating how auditory neural activity
contribute to the categorization of sounds. Single-unit responses were compared not only for a
library of pup USVs, but also for a library of adult male USVs that may play a courtship role in
male-female encounters (Liu et al., 2003; Holy & Guo, 2005). These latter USVs form a control
vocal category that overlaps in several acoustic features with pup USVs (i.e. duration, onset
frequency, onset frequency modulation), yet they do not gain the same heightened behavioral
relevance for maternal animals as pup USVs do.
Interestingly, only when responses to pup and adult USVs were compared in a cell-type
specific fashion, and not when single-unit were pooled together, did encoding differences
emerge between maternal and non-maternal animals. Within the putative interneuron subset,
whose transient-onset form of response to USVs was well-predicted by pure tone responses,
no difference between pup and adult USV responses was observed in either maternal or
non-maternal animals. This was somewhat expected, as these putative interneurons were
classified as such because of their predictable sensitivity to basic acoustic features at sound
onset, which was similar for both categories of USVs.
[PLACE FIGURE 3 NEAR HERE]
On the other hand, the putative pyramidal neuron subset shows more delayed and
occasionally sustained responses to USVs that are poorly-predicted by pure tone responses.
Interestingly, in this subset, there was a significantly enhanced evoked firing rate response to
the collection of pup compared to matched adult USVs in maternal animals, but not in
non-maternal animals (Shepard et al., 2015b). The physiological characteristics of putative
pyramidal neurons on average showed a longer peak-to-peak distance (thick-spiking cells) and
late onset of response (Lin & Liu, 2010). When classifying units simply by physiological
properties and looking within the subset of units that are thick-spiking and late-responding,
there is still an observed enhanced evoked firing rate in response to pup USVs can also be
seen among maternal animals (Fig. 3). This suggests that as behavioral relevance is acquired,
a physiologically definable neuronal subset begins to encode the combination of acoustic
features that define pup USVs in a manner that enhances this sound category’s overall ability to
elicit activity in downstream areas. In fact, the excitatory response of a given unit to pup USVs
compared to its response to matched adult USVs showed a greater difference in maternal
animals, a result that supports improved discrimination of acoustic features that separate the
former from the latter category (Shepard et al., 2015b).
3.4 Long-term Inhibitory Plasticity for Call Detection
The studies in Section 3.3 suggest that motherhood can alter the auditory encoding of
infant calls to improve categorization and discrimination of these sounds, potentially due in part
to maternal-related elevations in hormones such as estrogen or oxytocin. A third presumed
function of auditory processing of vocalizations is simple detection of sounds, whether in a quiet
or noisy background. Indeed, in the natural environment, mouse pups can be separated from
the nest, and in order for pups to survive to reproductive age, mouse mothers must be able to
detect the distress calls from their pups. These calls can be embedded within a highly
heterogeneous sound environment. One of the mechanisms by which detection of pup calls
may in principle be enhanced is through suppression of competing sounds in the environment.
In particular, suppressing sounds with frequencies outside the ultrasonic range could be
effective for improving the signal to noise ratio for call detection.
[PLACE FIGURE 4 NEAR HERE]
There is evidence for such an effect in post-weaning mouse mothers when compared to
pup-naïve females, who have not undergone the hormonal changes associated with pregnancy
and parturition (Galindo-Leon et al., 2009; Lin et al., 2013). As the cortical mapping studies
demonstrated, sites within core auditory cortical fields can be coarsely tuned to frequency, and
organized in a tonotopic (i.e. primary and anterior auditory fields) or non-tonotopic (UF) fashion.
Within these sites, individual neurons can either be excited, inhibited or non-responsive to
specific sounds, including USVs. Interestingly, call-inhibited neurons were found to be more
strongly inhibited in mothers compared to virgins, but only at sites where the population activity
(e.g. local field potential) was tuned to frequencies lower than that found in the USVs – the
so-called, “lateral band” fields (Fig. 4). In other words, neurons at sites within core auditory
cortex that “should not be” excited by USV’s were being more strongly suppressed in mothers,
while firing rates for those sites that “should be” excited (e.g. tuned >50 kHz or located in the
UF) were not significantly different between mothers and virgins. At a population level, this
enhances the population neural activity contrast for representing pup USVs over other
competing sounds outside of the expected frequency range of those vocalizations.
3.5 Sensory Plasticity While Becoming Maternal
The studies reviewed in Section 3 have clearly established the phenomenology of
long-term maternal sensory plasticity for infant cries and how this can be meaningful for the
functional auditory processing of those sounds. However, the question remains how such
changes come to be, and how an interaction between social experience and reproductive
hormones might facilitate this plasticity and its longevity. A number of recent studies have
begun to shed light on this by investigating neural activity during the period of pup care, whether
in lactating mothers or co-carers gaining experience caring for young pups.
[PLACE FIGURE 5 NEAR HERE]
One key neural mechanism that has emerged is the role of multimodal sensory
experience with pups. Maternal care has long been thought to be multimodal in nature (Beach &
Jaynes, 1956), though in mice, pup olfactory cues apparently hold particular importance for
controlling maternal responsiveness (Gandelman et al., 1971a; Gandelman et al., 1971b).
Recent research in mice now suggests that pup odors actually facilitate auditory processing of
vocal cues from pups (Cohen et al., 2011; Cohen & Mizrahi, 2015). Passing pup odors to
anesthetized lactating mothers (~4 days postpartum), but not pup-naïve virgin females,
significantly modulated both the spontaneous and evoked firing of auditory cortical neurons.
The resulting modulation in the signal-to-noise ratio was especially robust in cortical
interneurons (Fig. 5). This raises the possibility, which still requires further investigation, that the
coincidence of pup odors and vocalizations during the period of active pup care might produce
long-term inhibitory changes in auditory cortex that survive even in the absence of facilitating
pup odors (Galindo-Leon et al., 2009), though this could also depend on whether recording
sites are tuned to or below ultrasound frequencies. Such a finding would be reminiscent of the
inhibitory plasticity observed in the olfactory bulb of ewes that learn to recognize their lambs by
odor (Kendrick et al., 1992). Odor modulation may also facilitate changes in excitation, as the
same group recently reported a disinhibitory effect of odors on pyramidal neuron firing in
response to sounds (Cohen & Mizrahi, 2015). These data therefore increasingly hint at the
possibility that the olfactory system may help to “teach” other sensory modalities about the
behavioral relevance of their respective pup cues.
A role for reproductive hormones in mediating experience-dependent, higher-order
auditory plasticity in the maternal context is also becoming more apparent. Behaviorally, there
has long been evidence that the combination of maternal hormones and pup experience are
required for a so-called maternal memory effect, measured as a faster reestablishment of
maternal behavioral responsiveness to live pups days or weeks after initial exposure to pups
(Banerjee & Liu, 2013). Such hormone-experience interactions also apply to behavioral tests of
maternal auditory memories for recognizing pup USVs (Banerjee & Liu, 2013), as described in
Section 3 (Ehret & Koch, 1989; Lin et al., 2013). At the neural level, the sustained behavioral
salience of pup USVs for post-weaning mothers and virgin co-carers with recent pup care
experience, but not post-weaning co-carers with distant pup care experience, is tracked by the
strength of USV-evoked lateral band inhibition in these same animal groups (Lin et al., 2013).
These results suggest that experience alone (i.e. co-caring for pups) does not sustain a long
auditory memory (behavioral or neural) for pup USVs, but that combining the pup care
experience with a maternal physiological state can.
Many different reproductive hormones are active during pregnancy, parturition and
lactation to create the maternal physiological state, including estrogen, progesterone, oxytocin,
prolactin, and others. How each may contribute to learning and sustaining auditory memories
for pup cues is only beginning to be investigated. In particular, several studies suggest that
estrogens can be important for the auditory aspects of maternal behavior. For instance,
responsiveness to another pup vocalization, “wriggling calls” (Geissler & Ehret, 2002), by virgin
co-carers is dependent on the estrus cycle, suggesting that ovarian hormones regulate
motivational aspects of responding to pup cues (Ehret, 2009). In fact, in co-carers that have
been ovariectomized, 5 days of pup experience along with estradiol treatment is sufficient to
selectively recognize pup USVs, whereas the absence of estradiol during this duration of
experience is not sufficient (Koch & Ehret, 1989). Studies have also demonstrated this effect in
rats, in which the latency to retrieve pups decreases with a combination of experience and
hormonal priming, including estrogen (Fleming & Sarker, 1990).
As noted in Section 2.5, estrogens could be acting either directly or indirectly on the
auditory system to enhance maternal behavioral responses to pup calls, and more research is
needed to be able to elucidate this. One study of maternal plasticity in the subcortical auditory
pathway has begun to investigate this (Miranda et al., 2014). Mothers were found to exhibit a
decreased latency of tone-evoked responses of the auditory nerve and cochlear nucleus, as
inferred from the auditory brainstem response. The potential role of pup experience versus
hormones was then addressed by showing that intact co-carers could show similar (albeit
intermediate) latency decreases, but that estrogen manipulation alone to mimic the hormonal
state present during pregnancy was not sufficient to recapitulate the effect. Hence, experience
at a minimum, and potentially in concert with estrogen, are needed for this particular subcortical
auditory plasticity in the maternal context.
Oxytocin is another hormone that is important for maternal behavior and social
interactions in general, and which has now been implicated specifically in
experience-dependent auditory cortical plasticity for pup retrieval (Marlin et al., 2015). Oxytocin
receptor activation specifically in the left auditory cortex, but not in the right, was found to be
sufficient to accelerate maternal pup retrieval in initially pup-naïve mice. Importantly for the
issue of direct versus indirect modes of action, oxytocin receptors are expressed at higher
densities in the left auditory cortex compared to the right. Interestingly, communication sound
processing is thought to be lateralized to the left hemisphere, a behavioral result that was also
previously confirmed in mice (Ehret, 1987). How oxytocin action in auditory cortex could
facilitate a more rapid acquisition of pup retrieval information was then investigated through in
vivo patch clamp recordings from pyramidal neurons in anesthetized animals (Liu, 2015; Marlin
et al., 2015). Reminiscent of the odor-evoked disinhibition of auditory cortical activity discussed
above (Cohen & Mizrahi, 2015), oxytocin application was found to initially weaken USV-evoked
inhibitory currents, followed by strengthening of excitatory currents and a subsequent balancing
of excitation and inhibition (Fig. 6). Thus, oxytocin appears to play an enhancing, facilitating role
for allowing auditory cortical neurons to "tune" their excitatory and inhibitory inputs to relevant
social sounds.
[PLACE FIGURE 6 NEAR HERE]
The maternal mouse model of acoustic communication between pups and adult females
is providing a rich, natural behavioral context in which to investigate the electrophysiological
mechanisms by which sounds become meaningful. As new research is starting to elucidate,
reproductive hormones such as estrogen and oxytocin are likely playing important roles in both
the acquisition and maintenance of the auditory memories for these vocalizations.
4. Relevance to Human Maternal Hearing
As discussed here for mammals, non-human models have been highly suggestive in
implicating a role for reproductive hormones in auditory perception and learning (e.g., also see
Forlano et al., Chapter 2; Wilczynski & Burmeister, Chapter 3; Caras & Remage-Healey,
Chapter 4; Maney, Chapter 5). A natural next question would be whether such findings are
relevant to auditory processing in humans, particularly in the maternal context. Obviously, more
invasive experimental paradigms are not widely available for the investigation of auditory
encoding in humans, so evidence that reproductive hormones play a role in human audition
often emerges as indirect outcomes of ancillary studies. Nevertheless, accumulating research
has begun to hint at this interaction, as we now briefly review (also see Frisina & Frisina,
Chapter 7).
There is much interest in understanding the neurobiological (Swain et al., 2007) and
neuroendocrine (Swain et al., 2011) basis of human parent-infant relationships because of its
translational relevance for parental psychopathology, such as postpartum depression. Such
research often takes advantage of infant sensory stimuli, including baby faces (Bartels & Zeki,
2004) and sounds (Lorberbaum et al., 2002), to evoke neural responses in functional magnetic
resonance imaging (fMRI) studies of parents and non-parents. Such studies have generally
demonstrated activation of emotion and motivation areas of the brain, including the medial
preoptic area, hypothalamus, midbrain, cingulate cortex, amygdala, thalamus, and striatum
(Swain et al., 2007). Many that have specifically used infant vocalizations have found activation
in auditory cortical regions along the superior temporal gyrus, often at levels greater than for
matched control sounds (Lorberbaum et al., 2002; Swain et al., 2007), providing a reminder that
the use of ethologically relevant stimuli is important even for human studies.
Mirroring expectations from animal studies of experience-dependent changes with
motherhood, parental experience alters the pattern of fMRI activation in the amygdala and
associated limbic regions in response to sounds of infants crying (Seifritz et al., 2003). Strikingly,
there is even evidence that a mother’s own baby’s cry produces greater brain activation than a
stranger’s baby’s cry (Kim et al., 2011; Laurent & Ablow, 2012), an effect that is stronger in
auditory cortical regions for mothers who vaginally delivered their babies compared to those
that had a caesarean section (Swain et al., 2008). This presumably is due to the interaction of
hormones with experience hearing their babies cry, and may reflect the outcome of the
neurobiological processes explored in animal models. Indeed, studies show that breastfeeding
(Kim et al., 2011), or exogenously delivering either oxytocin (Riem et al., 2011) or testosterone
(Bos et al., 2010), can all modulate the pattern of brain activation by infant cries. Though some
of these effects are seen in regions of interest outside the auditory cortex itself, one possibility
could be that hormonal modulation is actually improving the ability of auditory information to be
fed forward to those areas. This is in line with an overarching hypothesis from the animal
studies that improved signal-to-noise representations in sensory areas could enhance
downstream processing (Banerjee & Liu, 2013; Shepard et al., 2015b), and that hormones like
oxytocin help to enhance this sensory representation (Marlin et al., 2015).
The hypothesis from the mouse studies that feedforward representations of infant cries
are altered by motherhood makes some predictions that could be tested in humans. For
example, the concept of lateral band inhibition described earlier suggests that in the presence
of a baby cry that is recognized as such, the sound of any background noise would be
suppressed. Though this particular experiment has not been carried out, there is an intriguing
parallel from psychophysical studies of speech perception wherein participants report a
subjective suppression of background noise when hearing familiar words spoken by a familiar
voice compared to an unfamiliar voice (Goldinger et al., 1999). The mouse studies would also
predict that the acoustic features of infant cries would trigger a heightened neural response in
mothers compared to control sounds (Shepard et al., 2015b). That this might happen in a purely
feedforward manner could be investigated by looking at mothers who are sleeping when they
hear babies cry. Night-waking to infant cries by mothers has in fact been shown to be mostly
indiscriminate within the first 48 hours after birth, after which mothers then wake specifically in
response to their own infant's cries and not to other infants' cries (Formby, 1967). Mothers are
also able to consciously report, based solely on the acoustics of the vocalization, whether an
infant cry belongs to their own baby or not (Green & Gustafson, 1983), demonstrating that
during maternity, mothers learn and become attuned to the acoustic cues of their own infants.
Hormones such as oxytocin have been shown to be particularly elevated during the early
postpartum period in mothers, potentially playing a role in this effect (Nissen et al., 1995;
Prevost et al., 2014). As administration of exogenous oxytocin has been shown in the mouse to
modulate auditory cortical responses to pup vocalizations (Marlin et al., 2015), oxytocin’s
presence postpartum may also be playing a similar role in humans. Additionally, estrogen,
which surges shortly before parturition (Challis JR, 1994), may also help prime the auditory
system for creating a long-lasting neural trace of infant auditory cues (Banerjee & Liu, 2013).
Hence, the neurophysiological principles elucidated through animal studies of the interaction of
hormones and experience on sensory representations can provide new insights into both
human hearing and parental behavior.
5. Summary
This chapter has illustrated how sensory processing changes in a way that is highly
dependent upon an interaction between both the external context, whether social or nonsocial,
and the neural substrate interpreting that context, i.e., the organism’s internal state, which
includes chemical modulators such as hormones. There is a growing need for research that
better integrates contextual effects on sensory processing, and hormones as a potential
mechanism that drives sensory processing changes. Whether principles extracted from one
paradigm, context, or hormonal system can be extended to others requires validation, due to
how variable responses of sensory systems are to each of these elements. However, by
understanding how multiple hormone systems can affect sensory processing in one particular
context, motherhood, a deeper understanding is possible of overarching principles that govern
sensory processing, what modulates it, and how hearing is affected by social interactions and
the hormones that respond to this context.
References
Apfelbach, R., Blanchard, C. D., Blanchard, R. J., Hayes, R. A., & McGregor, I. S. (2005). The
effects of predator odors in mammalian prey species: a review of field and laboratory
studies. Neuroscience and biobehavioral reviews, 29(8), 1123-1144. doi:
10.1016/j.neubiorev.2005.05.005
Balcombe, J. P. (1990). Vocal recognition of pups by mother Mexican free-tailed bats, Tadarida
brasiliensis mexicana. Animal Behaviour, 39(5), 960-966. doi:
http://dx.doi.org/10.1016/S0003-3472(05)80961-3
Banerjee, S. B., & Liu, R. C. (2013). Storing maternal memories: hypothesizing an interaction of
experience and estrogen on sensory cortical plasticity to learn infant cues. Frontiers in
neuroendocrinology, 34(4), 300-314. doi: 10.1016/j.yfrne.2013.07.008
Bartels, A., & Zeki, S. (2004). The neural correlates of maternal and romantic love. NeuroImage,
21(3), 1155-1166. doi: 10.1016/j.neuroimage.2003.11.003
Beach, F. A., & Jaynes, J. (1956). Studies of Maternal Retrieving in Rats. Iii. Sensory Cues
Involved in the Lactating Female's Response To Her Young 1). Behaviour, 10(1),
104-124. doi: doi:10.1163/156853956X00129
Bennur, S., Tsunada, J., Cohen, Y. E., & Liu, R. C. (2013). Understanding the
neurophysiological basis of auditory abilities for social communication: a perspective on
the value of ethological paradigms. Hearing research, 305, 3-9. doi:
10.1016/j.heares.2013.08.008
Berger, M., Gray, J. A., & Roth, B. L. (2009). The expanded biology of serotonin. Annual review
of medicine, 60, 355-366. doi: 10.1146/annurev.med.60.042307.110802
Bester-Meredith, J. K., Fancher, A. P., & Mammarella, G. E. (2015). Vasopressin Proves
Es-sense-tial: Vasopressin and the Modulation of Sensory Processing in Mammals.
Frontiers in endocrinology, 6, 5. doi: 10.3389/fendo.2015.00005
Bos, P. A., Hermans, E. J., Montoya, E. R., Ramsey, N. F., & van Honk, J. (2010). Testosterone
administration modulates neural responses to crying infants in young females.
Psychoneuroendocrinology, 35(1), 114-121. doi: 10.1016/j.psyneuen.2009.09.013
Brownstein, M. J., Russell, J. T., & Gainer, H. (1980). Synthesis, transport, and release of
posterior pituitary hormones. Science, 207(4429), 373-378.
Burkett, J. P., & Young, L. J. (2012). The behavioral, anatomical and pharmacological parallels
between social attachment, love and addiction. Psychopharmacology, 224(1), 1-26. doi:
10.1007/s00213-012-2794-x
Campbell, P., Ophir, A. G., & Phelps, S. M. (2009). Central vasopressin and oxytocin receptor
distributions in two species of singing mice. The Journal of comparative neurology,
516(4), 321-333. doi: 10.1002/cne.22116
Challis JR, L. S. (1994). Parturition. In N. J. Knobil E (Ed.), The Physiology of Reproduction (pp.
985-1031): New York: Raven Press.
Charitidi, K., & Canlon, B. (2010). Estrogen receptors in the central auditory system of male and
female mice. Neuroscience, 165(3), 923-933. doi: 10.1016/j.neuroscience.2009.11.020
Charitidi, K., Meltser, I., Tahera, Y., & Canlon, B. (2009). Functional responses of estrogen
receptors in the male and female auditory system. Hearing research, 252(1-2), 71-78.
doi: 10.1016/j.heares.2008.12.009
Chrousos, G. P. (1995). The Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated
Inflammation. New England Journal of Medicine, 332(20), 1351-1363. doi:
doi:10.1056/NEJM199505183322008
Chung, S., Son, G. H., & Kim, K. (2011). Circadian rhythm of adrenal glucocorticoid: its
regulation and clinical implications. Biochimica et biophysica acta, 1812(5), 581-591. doi:
10.1016/j.bbadis.2011.02.003
Cohen, L., & Mizrahi, A. (2015). Plasticity during motherhood: changes in excitatory and
inhibitory layer 2/3 neurons in auditory cortex. The Journal of neuroscience, 35(4),
1806-1815. doi: 10.1523/JNEUROSCI.1786-14.2015
Cohen, L., Rothschild, G., & Mizrahi, A. (2011). Multisensory integration of natural odors and
sounds in the auditory cortex. Neuron, 72(2), 357-369. doi:
10.1016/j.neuron.2011.08.019
Cruz, O. L., Kasse, C. A., Sanchez, M., Barbosa, F., & Barros, F. A. (2004). Serotonin reuptake
inhibitors in auditory processing disorders in elderly patients: preliminary results. The
Laryngoscope, 114(9), 1656-1659. doi: 10.1097/00005537-200409000-00029
Deemyad, T., Metzen, M. G., Pan, Y., & Chacron, M. J. (2013). Serotonin selectively enhances
perception and sensory neural responses to stimuli generated by same-sex conspecifics.
Proceedings of the National Academy of Sciences of the United States of America,
110(48), 19609-19614. doi: 10.1073/pnas.1314008110
Donaldson, Z. R., & Young, L. J. (2008). Oxytocin, vasopressin, and the neurogenetics of
sociality. Science, 322(5903), 900-904. doi: 10.1126/science.1158668
Edeline, J. M., Manunta, Y., & Hennevin, E. (2011). Induction of selective plasticity in the
frequency tuning of auditory cortex and auditory thalamus neurons by locus coeruleus
stimulation. Hearing research, 274(1-2), 75-84. doi: 10.1016/j.heares.2010.08.005
Ehret, G. (1987). Left hemisphere advantage in the mouse brain for recognizing ultrasonic
communication calls. Nature, 325(6101), 249-251. doi: 10.1038/325249a0
Ehret, G. (2005). Infant rodent ultrasounds -- a gate to the understanding of sound
communication. Behavior genetics, 35(1), 19-29. doi: 10.1007/s10519-004-0853-8
Ehret, G. (2009). New perspectives of information transformation through the auditory cortical
layers. Proceedings of the National Academy of Sciences of the United States of
America, 106(51), 21463-21464. doi: 10.1073/pnas.0912299107
Ehret, G., & Haack, B. (1984). Motivation and Arousal Influence Sound-induced Maternal
Pup-retrieving Behavior in Lactating House Mice. Zeitschrift für Tierpsychologie, 65(1),
25-39. doi: 10.1111/j.1439-0310.1984.tb00370.x
Ehret, G., & Koch, M. (1989). Ultrasound-Induced Parental Behavior in House Mice Is
Controlled by Female Sex-Hormones and Parental Experience. Ethology, 80(1-4),
81-93.
Ehret, G., Koch, M., Haack, B., & Markl, H. (1987). Sex and parental experience determine the
onset of an instinctive behavior in mice. Naturwissenschaften, 74(1), 47-47. doi:
10.1007/BF00367047
Euler, U. S. v., & Liljestrand, G. (1946). Observations on the Pulmonary Arterial Blood Pressure
in the Cat. Acta Physiologica Scandinavica, 12(4), 301-320. doi:
10.1111/j.1748-1716.1946.tb00389.x
Febo, M., Numan, M., & Ferris, C. F. (2005). Functional magnetic resonance imaging shows
oxytocin activates brain regions associated with mother-pup bonding during suckling.
The Journal of neuroscience, 25(50), 11637-11644. doi:
10.1523/JNEUROSCI.3604-05.2005
Fehm-Wolfsdorf, G., & Nagel, D. (1996). Differential effects of glucocorticoids on human
auditory perception. Biological psychology, 42(1-2), 117-130.
Fehm-Wolfsdorf, G., Soherr, U., Arndt, R., Kern, W., Fehm, H. L., & Nagel, D. (1993). Auditory
reflex thresholds elevated by stress-induced cortisol secretion.
Psychoneuroendocrinology, 18(8), 579-589.
Ferguson, J. N., Aldag, J. M., Insel, T. R., & Young, L. J. (2001). Oxytocin in the medial
amygdala is essential for social recognition in the mouse. The Journal of neuroscience,
21(20), 8278-8285.
Fink, G., Sumner, B. E., Rosie, R., Grace, O., & Quinn, J. P. (1996). Estrogen control of central
neurotransmission: effect on mood, mental state, and memory. Cellular and molecular
neurobiology, 16(3), 325-344.
Fleming, A. S., & Sarker, J. (1990). Experience-hormone interactions and maternal behavior in
rats. Physiology & behavior, 47(6), 1165-1173.
Forlano, P. M., Sisneros, J. A., Rohmann, K. N., & Bass, A. H. (2015). Neuroendocrine control
of seasonal plasticity in the auditory and vocal systems of fish. Frontiers in
neuroendocrinology, 37, 129-145. doi: 10.1016/j.yfrne.2014.08.002
Formby, D. (1967). Maternal recognition of infant's cry. Developmental medicine and child
neurology, 9(3), 293-298.
Gahr, M. (2001). Distribution of sex steroid hormone receptors in the avian brain: functional
implications for neural sex differences and sexual behaviors. Microscopy research and
technique, 55(1), 1-11. doi: 10.1002/jemt.1151
Galambos, R. (1956). Some recent experiments on the neurophysiology of hearing. The Annals
of otology, rhinology, and laryngology, 65(4), 1053-1059.
Galindo-Leon, E. E., Lin, F. G., & Liu, R. C. (2009). Inhibitory plasticity in a lateral band
improves cortical detection of natural vocalizations. Neuron, 62(5), 705-716. doi:
10.1016/j.neuron.2009.05.001
Galvez, R., Mesches, M. H., & McGaugh, J. L. (1996). Norepinephrine release in the amygdala
in response to footshock stimulation. Neurobiology of learning and memory, 66(3),
253-257. doi: 10.1006/nlme.1996.0067
Gandelman, R., Zarrow, M. X., & Denenberg, V. H. (1971a). Stimulus control of cannibalism
and maternal behavior in anosmic mice. Physiology & behavior, 7(4), 583-586.
Gandelman, R., Zarrow, M. X., Denenberg, V. H., & Myers, M. (1971b). Olfactory bulb removal
eliminates maternal behavior in the mouse. Science, 171(3967), 210-211.
Geissler, D. B., & Ehret, G. (2002). Time-critical integration of formants for perception of
communication calls in mice. Proceedings of the National Academy of Sciences of the
United States of America, 99(13), 9021-9025. doi: 10.1073/pnas.122606499
Geissler, D. B., Sabine Schmidt, H., & Ehret, G. (2013). Limbic brain activation for maternal
acoustic perception and responding is different in mothers and virgin female mice.
Journal of physiology, Paris, 107(1-2), 62-71. doi: 10.1016/j.jphysparis.2012.05.006
Goense, J. B., & Feng, A. S. (2005). Seasonal changes in frequency tuning and temporal
processing in single neurons in the frog auditory midbrain. Journal of neurobiology, 65(1),
22-36. doi: 10.1002/neu.20172
Goldinger, S. D., Kleider, H. M., & Shelley, E. (1999). The marriage of perception and memory:
creating two-way illusions with words and voices. Memory & cognition, 27(2), 328-338.
Goodson, J. L., & Bass, A. H. (2001). Social behavior functions and related anatomical
characteristics of vasotocin/vasopressin systems in vertebrates. Brain research. Brain
research reviews, 35(3), 246-265.
Green, J. A., & Gustafson, G. E. (1983). Individual recognition of human infants on the basis of
cries alone. Developmental psychobiology, 16(6), 485-493. doi: 10.1002/dev.420160604
Grimsley, J. M., Hazlett, E. G., & Wenstrup, J. J. (2013). Coding the meaning of sounds:
contextual modulation of auditory responses in the basolateral amygdala. The Journal of
neuroscience, 33(44), 17538-17548. doi: 10.1523/JNEUROSCI.2205-13.2013
Halene, T. B., Talmud, J., Jonak, G. J., Schneider, F., & Siegel, S. J. (2009). Predator odor
modulates auditory event-related potentials in mice. Neuroreport, 20(14), 1260-1264.
doi: 10.1097/WNR.0b013e3283300cde
Hall, I. C., Rebec, G. V., & Hurley, L. M. (2010). Serotonin in the inferior colliculus fluctuates
with behavioral state and environmental stimuli. The Journal of experimental biology,
213(Pt 7), 1009-1017. doi: 10.1242/jeb.035956
Hall, I. C., Sell, G. L., & Hurley, L. M. (2011). Social regulation of serotonin in the auditory
midbrain. Behavioral neuroscience, 125(4), 501-511. doi: 10.1037/a0024426
Han, Y. K., Kover, H., Insanally, M. N., Semerdjian, J. H., & Bao, S. (2007). Early experience
impairs perceptual discrimination. Nature neuroscience, 10(9), 1191-1197. doi:
10.1038/nn1941
Hanson, J. L., & Hurley, L. M. (2014). Context-dependent fluctuation of serotonin in the auditory
midbrain: the influence of sex, reproductive state and experience. The Journal of
experimental biology, 217(Pt 4), 526-535. doi: 10.1242/jeb.087627
Harley, C. W. (1987). A role for norepinephrine in arousal, emotion and learning?: limbic
modulation by norepinephrine and the Kety hypothesis. Progress in
neuro-psychopharmacology & biological psychiatry, 11(4), 419-458.
Holy, T. E., & Guo, Z. (2005). Ultrasonic songs of male mice. PLoS biology, 3(12), e386. doi:
10.1371/journal.pbio.0030386
Hurley, L. M., & Sullivan, M. R. (2012). From behavioral context to receptors: serotonergic
modulatory pathways in the IC. Frontiers in neural circuits, 6, 58. doi:
10.3389/fncir.2012.00058
Hurley, L. M., Devilbiss, D. M., & Waterhouse, B. D. (2004). A matter of focus: monoaminergic
modulation of stimulus coding in mammalian sensory networks. Current opinion in
neurobiology, 14(4), 488-495. doi: 10.1016/j.conb.2004.06.007
Jensen, G. D. (1965). Mother-Infant Relationship in the Monkey Macaca Nemestrina:
Development of Specificity of Maternal Response to Own Infant. Journal of comparative
and physiological psychology, 59, 305-308.
Ji, W., & Suga, N. (2007). Serotonergic modulation of plasticity of the auditory cortex elicited by
fear conditioning. The Journal of neuroscience, 27(18), 4910-4918. doi:
10.1523/JNEUROSCI.5528-06.2007
Johnson, R. G., Stevens, K. E., & Rose, G. M. (1998). 5-Hydroxytryptamine2 receptors
modulate auditory filtering in the rat. The Journal of pharmacology and experimental
therapeutics, 285(2), 643-650.
Kaas, J. H., & Hackett, T. A. (2000). Subdivisions of auditory cortex and processing streams in
primates. Proceedings of the National Academy of Sciences of the United States of
America, 97(22), 11793-11799. doi: 10.1073/pnas.97.22.11793
Kanwal, J. S., & Rao, P. D. (2002). Oxytocin within auditory nuclei: a neuromodulatory function
in sensory processing? Neuroreport, 13(17), 2193-2197. doi:
10.1097/01.wnr.0000044220.09266.0d
Kawata, M. (1995). Roles of steroid hormones and their receptors in structural organization in
the nervous system. Neuroscience research, 24(1), 1-46.
Keller, M., Meurisse, M., Poindron, P., Nowak, R., Ferreira, G., Shayit, M., & Levy, F. (2003).
Maternal experience influences the establishment of visual/auditory, but not olfactory
recognition of the newborn lamb by ewes at parturition. Developmental psychobiology,
43(3), 167-176. doi: 10.1002/dev.10130
Kendrick, K. M., Levy, F., & Keverne, E. B. (1992). Changes in the sensory processing of
olfactory signals induced by birth in sheep. Science, 256(5058), 833-836.
Kim, P., Feldman, R., Mayes, L. C., Eicher, V., Thompson, N., Leckman, J. F., & Swain, J. E.
(2011). Breastfeeding, brain activation to own infant cry, and maternal sensitivity. Journal
of child psychology and psychiatry, and allied disciplines, 52(8), 907-915. doi:
10.1111/j.1469-7610.2011.02406.x
Kirsch, P., Esslinger, C., Chen, Q., Mier, D., Lis, S., Siddhanti, S., Gruppe, H., Mattay, V. S.,
Gallhofer, B., & Meyer-Lindenberg, A. (2005). Oxytocin modulates neural circuitry for
social cognition and fear in humans. The Journal of neuroscience, 25(49), 11489-11493.
doi: 10.1523/JNEUROSCI.3984-05.2005
Koch, M., & Ehret, G. (1989). Estradiol and parental experience, but not prolactin are necessary
for ultrasound recognition and pup-retrieving in the mouse. Physiology & behavior, 45(4),
771-776.
Kritzer, M. F. (2002). Regional, laminar, and cellular distribution of immunoreactivity for ER
alpha and ER beta in the cerebral cortex of hormonally intact, adult male and female rats.
Cerebral cortex, 12(2), 116-128.
Lambert, G. W., Reid, C., Kaye, D. M., Jennings, G. L., & Esler, M. D. (2002). Effect of sunlight
and season on serotonin turnover in the brain. Lancet, 360(9348), 1840-1842.
Laurent, H. K., & Ablow, J. C. (2012). A cry in the dark: depressed mothers show reduced
neural activation to their own infant's cry. Social cognitive and affective neuroscience,
7(2), 125-134. doi: 10.1093/scan/nsq091
Lesch, K.-P., Wolozin, B. L., Murphy, D. L., & Riederer, P. (1993). Primary Structure of the
Human Platelet Serotonin Uptake Site: Identity with the Brain Serotonin Transporter.
Journal of Neurochemistry, 60(6), 2319-2322. doi: 10.1111/j.1471-4159.1993.tb03522.x
Lin, F. G., & Liu, R. C. (2010). Subset of thin spike cortical neurons preserve the peripheral
encoding of stimulus onsets. Journal of neurophysiology, 104(6), 3588-3599. doi:
10.1152/jn.00295.2010
Lin, F. G., Galindo-Leon, E. E., Ivanova, T. N., Mappus, R. C., & Liu, R. C. (2013). A role for
maternal physiological state in preserving auditory cortical plasticity for salient infant
calls. Neuroscience, 247, 102-116. doi: 10.1016/j.neuroscience.2013.05.020
Liu, R. C. (2015). Sensory systems: The yin and yang of cortical oxytocin. Nature, 520(7548),
444-445. doi: 10.1038/nature14386
Liu, R. C., & Schreiner, C. E. (2007). Auditory cortical detection and discrimination correlates
with communicative significance. PLoS biology, 5(7), e173. doi:
10.1371/journal.pbio.0050173
Liu, R. C., Linden, J. F., & Schreiner, C. E. (2006). Improved cortical entrainment to infant
communication calls in mothers compared with virgin mice. European Journal of
Neuroscience, 23(11), 3087-3097. doi: 10.1111/j.1460-9568.2006.04840.x
Liu, R. C., Miller, K. D., Merzenich, M. M., & Schreiner, C. E. (2003). Acoustic variability and
distinguishability among mouse ultrasound vocalizations. The Journal of the Acoustical
Society of America, 114(6 Pt 1), 3412-3422.
Lorberbaum, J. P., Newman, J. D., Horwitz, A. R., Dubno, J. R., Lydiard, R. B., Hamner, M. B.,
Bohning, D. E., & George, M. S. (2002). A potential role for thalamocingulate circuitry in
human maternal behavior. Biological psychiatry, 51(6), 431-445.
Lotze, M., Wittmann, M., von Steinbuchel, N., Poppel, E., & Roenneberg, T. (1999). Daily
rhythm of temporal resolution in the auditory system. Cortex, 35(1), 89-100.
Maney, D. L., Cho, E., & Goode, C. T. (2006). Estrogen-dependent selectivity of genomic
responses to birdsong. The European journal of neuroscience, 23(6), 1523-1529. doi:
10.1111/j.1460-9568.2006.04673.x
Manunta, Y., & Edeline, J.-M. (1997). Effects of Noradrenaline on Frequency Tuning of Rat
Auditory Cortex Neurons. European Journal of Neuroscience, 9(4), 833-847. doi:
10.1111/j.1460-9568.1997.tb01433.x
Marlin, B. J., Mitre, M., D'Amour J, A., Chao, M. V., & Froemke, R. C. (2015). Oxytocin enables
maternal behaviour by balancing cortical inhibition. Nature, 520(7548), 499-504. doi:
10.1038/nature14402
Martins, A. R., & Froemke, R. C. (2015). Coordinated forms of noradrenergic plasticity in the
locus coeruleus and primary auditory cortex. Nature neuroscience. doi: 10.1038/nn.4090
Maxwell, C. R., Ehrlichman, R. S., Liang, Y., Gettes, D. R., Evans, D. L., Kanes, S. J., Abel, T.,
Karp, J., & Siegel, S. J. (2006). Corticosterone modulates auditory gating in mouse.
Neuropsychopharmacology, 31(5), 897-903. doi: 10.1038/sj.npp.1300879
Mazurek, B., Haupt, H., Joachim, R., Klapp, B. F., Stover, T., & Szczepek, A. J. (2010). Stress
induces transient auditory hypersensitivity in rats. Hearing research, 259(1-2), 55-63.
doi: 10.1016/j.heares.2009.10.006
McCormick, D. A., Connors, B. W., Lighthall, J. W., & Prince, D. A. (1985). Comparative
electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex.
Journal of neurophysiology, 54(4), 782-806.
McGaugh, J. L. (2000). Memory--a century of consolidation. Science, 287(5451), 248-251.
McNeilly, A. S., Robinson, I. C., Houston, M. J., & Howie, P. W. (1983). Release of oxytocin and
prolactin in response to suckling. British medical journal, 286(6361), 257-259.
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011). Oxytocin and vasopressin
in the human brain: social neuropeptides for translational medicine. Nature reviews.
Neuroscience, 12(9), 524-538. doi: 10.1038/nrn3044
Miranda, J. A., & Liu, R. C. (2009). Dissecting natural sensory plasticity: hormones and
experience in a maternal context. Hearing research, 252(1-2), 21-28. doi:
10.1016/j.heares.2009.04.014
Miranda, J. A., Shepard, K. N., McClintock, S. K., & Liu, R. C. (2014). Adult plasticity in the
subcortical auditory pathway of the maternal mouse. PloS one, 9(7), e101630. doi:
10.1371/journal.pone.0101630
Morimoto, M., Morita, N., Ozawa, H., Yokoyama, K., & Kawata, M. (1996). Distribution of
glucocorticoid receptor immunoreactivity and mRNA in the rat brain: an
immunohistochemical and in situ hybridization study. Neuroscience research, 26(3),
235-269.
Munaut, C., Lambert, V., Noël, A., Frankenne, F., Deprez, M., Foidart, J.-M., & Rakic, J.-M.
(2001). Presence of oestrogen receptor type β in human retina. British Journal of
Ophthalmology, 85(7), 877-882. doi: 10.1136/bjo.85.7.877
Naganuma, H., Kawahara, K., Tokumasu, K., Satoh, R., & Okamoto, M. (2014). Effects of
arginine vasopressin on auditory brainstem response and cochlear morphology in rats.
Auris, nasus, larynx, 41(3), 249-254. doi: 10.1016/j.anl.2013.12.004
Neubauer, H., & Heil, P. (2008). A physiological model for the stimulus dependence of
first-spike latency of auditory-nerve fibers. Brain research, 1220, 208-223. doi:
10.1016/j.brainres.2007.08.081
Nissen, E., Lilja, G., Widstrom, A. M., & Uvnas-Moberg, K. (1995). Elevation of oxytocin levels
early post partum in women. Acta obstetricia et gynecologica Scandinavica, 74(7),
530-533.
Ogueta, S. B., Schwartz, S. D., Yamashita, C. K., & Farber, D. B. (1999). Estrogen receptor in
the human eye: influence of gender and age on gene expression. Investigative
ophthalmology & visual science, 40(9), 1906-1911.
Perrodin, C., Kayser, C., Logothetis, N. K., & Petkov, C. I. (2011). Voice cells in the primate
temporal lobe. Current biology, 21(16), 1408-1415. doi: 10.1016/j.cub.2011.07.028
Poindron, P., Le Neindre, P., Raksanyi, I., Trillat, G., & Orgeur, P. (1980). Importance of the
characteristics of the young in the manifestation and establishment of maternal
behaviour in sheep. Reproduction, nutrition, development, 20(3B), 817-826.
Prevost, M., Zelkowitz, P., Tulandi, T., Hayton, B., Feeley, N., Carter, C. S., Joseph, L.,
Pournajafi-Nazarloo, H., Yong Ping, E., Abenhaim, H., & Gold, I. (2014). Oxytocin in
pregnancy and the postpartum: relations to labor and its management. Frontiers in public
health, 2, 1. doi: 10.3389/fpubh.2014.00001
Recanzone, G. H., Schreiner, C. E., & Merzenich, M. M. (1993). Plasticity in the frequency
representation of primary auditory cortex following discrimination training in adult owl
monkeys. The Journal of neuroscience, 13(1), 87-103.
Reed, A., Riley, J., Carraway, R., Carrasco, A., Perez, C., Jakkamsetti, V., & Kilgard, M. P.
(2011). Cortical map plasticity improves learning but is not necessary for improved
performance. Neuron, 70(1), 121-131. doi: 10.1016/j.neuron.2011.02.038
Remage-Healey, L., Coleman, M. J., Oyama, R. K., & Schlinger, B. A. (2010). Brain estrogens
rapidly strengthen auditory encoding and guide song preference in a songbird.
Proceedings of the National Academy of Sciences of the United States of America,
107(8), 3852-3857. doi: 10.1073/pnas.0906572107
Reul, J. M., & de Kloet, E. R. (1985). Two receptor systems for corticosterone in rat brain:
microdistribution and differential occupation. Endocrinology, 117(6), 2505-2511. doi:
10.1210/endo-117-6-2505
Riem, M. M., Bakermans-Kranenburg, M. J., Pieper, S., Tops, M., Boksem, M. A., Vermeiren, R.
R., van Ijzendoorn, M. H., & Rombouts, S. A. (2011). Oxytocin modulates amygdala,
insula, and inferior frontal gyrus responses to infant crying: a randomized controlled trial.
Biological psychiatry, 70(3), 291-297. doi: 10.1016/j.biopsych.2011.02.006
Searcy, W. A., & Marler, P. (1981). A test for responsiveness to song structure and
programming in female sparrows. Science, 213(4510), 926-928. doi:
10.1126/science.213.4510.926
Seifritz, E., Esposito, F., Neuhoff, J. G., Luthi, A., Mustovic, H., Dammann, G., von Bardeleben,
U., Radue, E. W., Cirillo, S., Tedeschi, G., & Di Salle, F. (2003). Differential
sex-independent amygdala response to infant crying and laughing in parents versus
nonparents. Biological psychiatry, 54(12), 1367-1375.
Semsar, K., Kandel, F. L., & Godwin, J. (2001). Manipulations of the AVT system shift social
status and related courtship and aggressive behavior in the bluehead wrasse. Hormones
and behavior, 40(1), 21-31. doi: 10.1006/hbeh.2001.1663
Shepard, K. N., Kilgard, M. P., & Liu, R. C. (2012). Experience-Dependent Plasticity and the
Auditory Cortex. In Y. E. Cohen, A. N. Popper & R. R. Fay (Eds.), Neural correlates of
auditory cognition (Vol. 45, pp. 293-327). New York: Springer.
Shepard, K. N., Liles, L. C., Weinshenker, D., & Liu, R. C. (2015a). Norepinephrine is necessary
for experience-dependent plasticity in the developing mouse auditory cortex. The
Journal of neuroscience, 35(6), 2432-2437. doi: 10.1523/JNEUROSCI.0532-14.2015
Shepard, K. N., Lin, F. G., Zhao, C. L., Chong, K. K., & Liu, R. C. (2015b). Behavioral relevance
helps untangle natural vocal categories in a specific subset of core auditory cortical
pyramidal neurons. The Journal of neuroscience, 35(6), 2636-2645. doi:
10.1523/JNEUROSCI.3803-14.2015
Sisneros, J. A., Forlano, P. M., Deitcher, D. L., & Bass, A. H. (2004). Steroid-dependent
auditory plasticity leads to adaptive coupling of sender and receiver. Science, 305(5682),
404-407. doi: 10.1126/science.1097218
Stiebler, I., Neulist, R., Fichtel, I., & Ehret, G. (1997). The auditory cortex of the house mouse:
left-right differences, tonotopic organization and quantitative analysis of frequency
representation. Journal of comparative physiology, 181(6), 559-571.
Sugino, K., Hempel, C. M., Miller, M. N., Hattox, A. M., Shapiro, P., Wu, C., Huang, Z. J., &
Nelson, S. B. (2006). Molecular taxonomy of major neuronal classes in the adult mouse
forebrain. Nature neuroscience, 9(1), 99-107. doi: 10.1038/nn1618
Swain, J. E., Kim, P., & Ho, S. S. (2011). Neuroendocrinology of parental response to baby-cry.
Journal of neuroendocrinology, 23(11), 1036-1041. doi:
10.1111/j.1365-2826.2011.02212.x
Swain, J. E., Lorberbaum, J. P., Kose, S., & Strathearn, L. (2007). Brain basis of early
parent-infant interactions: psychology, physiology, and in vivo functional neuroimaging
studies. Journal of child psychology and psychiatry, and allied disciplines, 48(3-4),
262-287. doi: 10.1111/j.1469-7610.2007.01731.x
Swain, J. E., Tasgin, E., Mayes, L. C., Feldman, R., Constable, R. T., & Leckman, J. F. (2008).
Maternal brain response to own baby-cry is affected by cesarean section delivery.
Journal of child psychology and psychiatry, and allied disciplines, 49(10), 1042-1052.
doi: 10.1111/j.1469-7610.2008.01963.x
Swain, J. E., Kim, P., Spicer, J., Ho, S. S., Dayton, C. J., Elmadih, A., & Abel, K. M. (2014).
Approaching the biology of human parental attachment: brain imaging, oxytocin and
coordinated assessments of mothers and fathers. Brain research, 1580, 78-101. doi:
10.1016/j.brainres.2014.03.007
Swenson, R. M., & Vogel, W. H. (1983). Plasma Catecholamine and corticosterone as well as
brain catecholamine changes during coping in rats exposed to stressful footshock.
Pharmacology, biochemistry, and behavior, 18(5), 689-693.
ten Cate, W. J., Curtis, L. M., Small, G. M., & Rarey, K. E. (1993). Localization of glucocorticoid
receptors and glucocorticoid receptor mRNAs in the rat cochlea. The Laryngoscope,
103(8), 865-871. doi: 10.1288/00005537-199308000-00007
Tobin, V. A., Hashimoto, H., Wacker, D. W., Takayanagi, Y., Langnaese, K., Caquineau, C.,
Noack, J., Landgraf, R., Onaka, T., Leng, G., Meddle, S. L., Engelmann, M., & Ludwig, M.
(2010). An intrinsic vasopressin system in the olfactory bulb is involved in social
recognition. Nature, 464(7287), 413-417. doi: 10.1038/nature08826
Tops, M., van Ijzendoorn, M. H., Riem, M. M., Boksem, M. A., & Bakermans-Kranenburg, M. J.
(2011). Oxytocin receptor gene associated with the efficiency of social auditory
processing. Frontiers in psychiatry, 2, 60. doi: 10.3389/fpsyt.2011.00060
Trillmich, F. (1981). Mutual Mother-Pup Recognition in Galápagos Fur Seals and Sea Lions:
Cues Used and Functional Significance. Behaviour, 78(1/2), 21-42. doi:
10.2307/4534129
Tsanov, M., & Manahan-Vaughan, D. (2007). The adult visual cortex expresses dynamic
synaptic plasticity that is driven by the light/dark cycle. The Journal of neuroscience,
27(31), 8414-8421. doi: 10.1523/JNEUROSCI.1101-07.2007
Tsigos, C., & Chrousos, G. P. (2002). Hypothalamic-pituitary-adrenal axis, neuroendocrine
factors and stress. Journal of psychosomatic research, 53(4), 865-871.
Twarog, B. M., & Page, I. H. (1953). Serotonin content of some mammalian tissues and urine
and a method for its determination. The American journal of physiology, 175(1), 157-161.
Weinberger, N. M. (2004). Specific long-term memory traces in primary auditory cortex. Nature
reviews. Neuroscience, 5(4), 279-290. doi: 10.1038/nrn1366
Wersinger, S. R., Ginns, E. I., O'Carroll, A. M., Lolait, S. J., & Young, W. S., 3rd. (2002).
Vasopressin V1b receptor knockout reduces aggressive behavior in male mice.
Molecular psychiatry, 7(9), 975-984. doi: 10.1038/sj.mp.4001195
Wiesel, T. N., & Hubel, D. H. (1963). Single-Cell Responses in Striate Cortex of Kittens
Deprived of Vision in One Eye. Journal of neurophysiology, 26, 1003-1017.
Wu, M. V., Manoli, D. S., Fraser, E. J., Coats, J. K., Tollkuhn, J., Honda, S., Harada, N., & Shah,
N. M. (2009). Estrogen masculinizes neural pathways and sex-specific behaviors. Cell,
139(1), 61-72. doi: 10.1016/j.cell.2009.07.036
Yoder, K. M., Lu, K., & Vicario, D. S. (2012). Blocking estradiol synthesis affects memory for
songs in auditory forebrain of male zebra finches. Neuroreport, 23(16), 922-926. doi:
10.1097/WNR.0b013e3283588b61
Yovanof, S., & Feng, A. S. (1983). Effects of estradiol on auditory evoked responses from the
frog's auditory midbrain. Neuroscience letters, 36(3), 291-297.
Figure Legends:
Figure 1. Maternal mice show sustained preference for pup ultrasonic vocalizations (USVs). (A)
Schematic of two-alternative test for pup call preference. Vertical gray boxes represent
speakers playing pure tones (right) or pup USVs (left). Stimulus amplitude waveforms and
spectrograms are shown above. Thin line in W-maze schematic shows animal’s center-of-mass
movement in center region (light gray), past left arm (gray), and past right arm (black). (B) Call
to tone approach ratios among animal groups. Post-weaning mothers (black) and early
co-carers with 6-11 days of pup experience (gray) approach the pup call speaker significantly
more often than the tone speaker, whereas post-weaning co-carers (white) did not show
preferential approach to either side. (Reprinted from Lin et al. [2013] with permission from
Elsevier)
Figure 2. Entrainment of multiunit responses to mouse pup ultrasonic vocalizations (USVs)
improved in mothers versus virgins. Normalized pup call entrainment functions for post-weaning
mothers (light gray) and naïve females (dark gray) presented with pup USVs at varying
repetition rates under anesthesia (ketamine/medetomidine). Dashed line represents natural pup
USV frequency of 5 Hz. (Reprinted from Liu et al. [2006] with permission from John Wiley and
Sons)
Figure 3. Auditory cortical excitatory plasticity in thick-spiking, late-responding neural subsets of
maternal mice. Evoked firing rates of thick-spiking (peak-to-peak > 0.35ms) and
late-responding (onset of PSTH peak 18.9ms, median split) from mouse auditory cortex in
response to pup ultrasonic vocalizations (USVs) (green) and onset frequency /
duration-matched adult USVs (orange). SNR normalized by dividing firing rate by spontaneous
rate; stimulus presentation represented by dashed line at 0ms. Top: SU responses in
non-maternal animals; Bottom: SU responses in maternal animals. Enhanced evoked firing rate
in maternal (Mothers, post-weaning + Early co-carers) thick-spiking neurons specifically in
response to pup USVs over adult USVs, and not in non-maternal (Late co-carers + naïve
virgins) thick-spiking neurons. (Data from Shepard et al. [2015b])
Figure 4. Lateral band inhibition enhanced in maternal mice. Top panels show sample rasters
and PSTHs from single units recorded in laterally tuned auditory cortex of post-weaning mouse
mothers: (A) Ultrasonic vocalization (USV¥-excited neuron, (B) USV-inhibited neuron, (C) USV
non-responsive neuron. (D) Schematic of mouse auditory cortex showing enhanced contrast in
mothers’ population representation of pup calls through stronger pup call-evoked inhibition in
mothers’ lateral band fields, primary auditory field (A1) and anterior auditory field (AAF).
(Reprinted from Banerjee et al. [2013] with permission from Elsevier)
Figure 5. Interneurons in lactating mothers show more odor-enhanced activity in auditory cortex
in response to pup ultrasonic vocalizations (USVs). Larger modulation index values indicate
greater modulation of auditory cortical neural activity by pup odor during pup USV presentation.
LM: Lactating mother (P4), EV: Experienced Virgin, MFW: Mother Following Weaning, NV:
Naïve Virgin. *p=0.05; **p=0.01; ***p<0.001. (Reprinted from Cohen et al. [2011] with
permission from Elsevier)
Figure 6. Oxytocin pairing with pup ultrasonic vocalizations (USVs) in pup-naïve virgins. Initially,
such pairing weakens inhibition before strengthening excitation and balancing
excitatory-inhibitory drives to auditory cortical neurons. Voltage clamp recordings from virgins
treated with exogenous oxytocin at time 0 indicated by horizontal gray bar. Solid triangles (E)
show EPSCs, empty triangles (I) show IPSCs in response to pup USVs. Virgins show initial dip
in IPSC amplitude followed by increased EPSC and IPSC amplitude during oxytocin pairing
with pup USVs. (Reprinted from Marlin et al. [2015] with permission from Macmillan Publishers
Limited)
Fig. 1
A
B
* p<0.05
Fig. 2
Fig. 3
(Color)
Mother Virgin
A B C
Fig. 4 USV Exc USV Inh USV NR
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... The findings of seasonal shifts in the sense of hearing in midshipman fish are complemented by more recent studies in songbirds showing seasonal changes in hearing (e.g., see Caras, 2013;V?lez et al., 2015; and references therein). These studies, together with those showing the influence of steroids on seasonal peripheral auditory function in midshipman, complement studies in other teleosts (e.g., Maruska et al., 2012;Zeyl et al., 2013), birds ( Gall et al., 2013) and mammals, including humans (e.g., Chong and Liu, 2016;Frisina and Frisina, 2016). Peripheral action of estradiol is likely mediated by ERs located in auditory hair cells in midshipman (see above), as well as in birds and mammals (Hultcrantz et al., 2006;Noirot et al., 2009). ...
... The findings of seasonal shifts in the sense of hearing in midshipman fish are complemented by more recent studies in songbirds showing seasonal changes in hearing (e.g., see Caras, 2013;Vélez et al., 2015;and references therein). These studies, together with those showing the influence of steroids on seasonal peripheral auditory function in midshipman, complement studies in other teleosts (e.g., Maruska et al., 2012;Zeyl et al., 2013), birds (Gall et al., 2013) and mammals, including humans (e.g., Chong and Liu, 2016;Frisina and Frisina, 2016). Peripheral action of estradiol is likely mediated by ERs located in auditory hair cells in midshipman (see above), as well as in birds and mammals (Hultcrantz et al., 2006;Noirot et al., 2009). ...
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