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Sensory systems: The yin and yang of cortical oxytocin

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Abstract

Female mice can learn to respond to distress calls from young mice - an ability that has now been found to be improved through signalling by the hormone oxytocin in the left auditory cortex of the brain.
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... The ancient Yin-Yang theory is widely applied today to explain opposite but inter-dependent matters and imbalance within our body. 47,48 Decreased serum albumin values with an increase in globulin levels observed in RA is in accordance with the TCM school of thought that advocates insufficient Yin while excess Yang is the common factor facilitating pathogenesis shared by most disorders. Our research determined a significant correlation between decreased A/G ratio and dyslipidemia as well as ARDs in RA patients. ...
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Purpose Inflamm-aging is a novel-concept in rheumatoid arthritis (RA) with accelerating aging process. We try to find a correlation between serum albumin/globulin (A/G) ratio and clinical biochemical parameters, incidence of aging-related diseases (ARDs) as well as inflammaging-related molecules. Patients and Methods Healthy controls (HC) and RA patients were compared with their clinical biochemical parameters including albumin and globulin levels, A/G ratio, and levels of serum lipids. Incidence of ARDs in RA was compared with A/G ratio, having a cut off value of 1.2. Expression levels of leptin and Trf2 genes in PBMCs, and inflammatory factors like IL-1β, IL-6, IL-8 and TNF-ɑ between HC and RA patients were compared, and correlated with the A/G ratio. Results Compared to HC, RA patients had decreased levels of albumin, while globulin levels were found to be increased, which led to a significantly lower A/G ratio in RA patients. A/G ratio rather than ESR and CRP had significant correlation with dyslipidemia in RA patients. Patients with A/G <1.2 had a higher risk of ARDs than patients with A/G >1.2. The RR was 2.48 (95% CI: 1.79 to 3.64, p <0.0001). In addition, A/G ratio has positively correlated to leptin and Trf2 expression, while an inverse correlation was observed with the levels of inflamm-aging related cytokines like IL-6, IL-8 and TNF-ɑ. Conclusion A decreased A/G ratio in RA patients has significantly correlated with dyslipidemia and ARDs, as well as inflammaging- related adipokine and pro-inflammatory cytokines. Thus, A/G ratio could be a reliable marker for evaluating the inflammaging process during clinical management in ARDs.
... Different from males, females show cyclic peaks in sexual desire and excitability around the time of ovulation (Georgiadis et al. 2012). Modulation of cortical representation by maternity has been documented in somatosensory cortex (Xerri et al. 1994) and auditory cortex (Miranda et al. 2014, Liu 2015, Marlin et al, 2015. ...
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Die Arbeit untersucht die Neurophysiologie von zwei relevanten Berührungen: Die Vibrissenberührung von Artgenossen und die Berührung der Genitalien. Im ersten Teil, habe ich durch in vivo Ganzzellableitungen vom Barrel Kortex in kopf-fixierten Ratten untersucht, wie die Membranpotentialaktivität durch das Berühren einer Ratte aussieht. Während der Berührung von Artgenossen waren die Vibrissenbewegungen mit starken Membranpotentialänderungen assoziiert. Bei der spontanen Vibrissenbewegung wurden die Korrelationen nicht beobachtet. Weiterhin traten die Membranpotenzialfluktuationen bereits auf, bevor die Tiere sich berührten. Dies wurde allerdings nicht in anesthetisierten Ratten beobachtet. Zusätzlich waren die mit der Vibrissenberührung korrelierten Membranpotenzialfluktuationen größer, wenn die Tiere einen Artgenossen berührten verglichen zu Nichtartgenossen. Zusammenfassend, löst eine Berührung durch einen Artgenossen, sehr unterschiedlichere neuronale Antworten im Barrel Kortex aus, als konventionelle taktile Stimuli. Der zweite Teil untersucht den Genital Kortex. Die Charakterisierung der rezeptiven Felder demonstrierte eine robuste Repräsentation der Genitalien im sensorischen Kortex. Neuronale Antworten waren häufiger im Genital Kortex von Männchen als von Weibchen zu finden. Neurone zeigten diskontinuierliche und sexuell dimorphe rezeptive Felder. In Männchen, waren Neurone durch die taktile Stimulation des Vorderarms co-aktiviert, die Neurone in Weibchen eher durch die taktile Stimulation des Rumpfs. Diese mit den Genitalien ko-repräsentierten Körperteile, kommen während der Kopulation von Männchen und Weibchen in Berührung. Cytochrom Oxidase Färbungen von Schicht 4 zeigen einen Monomorphismus von kortikaler Penis und Klitoris Repräsentation. Dies ist in Hinsicht auf den Dimorphismus der externen Genitalien ein überraschendes Ergebnis. Zusätzlich wurde ein massives Wachstum des Genital Kortex während der Pubertät gefunden.
... 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). ...
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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.
... Different from males, females show cyclic peaks in sexual desire and excitability around the time of ovulation [21]. Modulation of cortical representation by maternity has been documented in somatosensory cortex [22] and auditory cortex [23][24][25]. Whether genital cortex responses are cycling with the sexual state of females, as it was shown in the ventromedial hypothalamus of mice [26], needs to be explored in recordings in awake animals. ...
Article
Mammalian external genitals show sexual dimorphism [1 and 2] and can change size and shape upon sexual arousal. Genitals feature prominently in the oldest pieces of figural art [3] and phallic depictions of penises informed psychoanalytic thought about sexuality [4 and 5]. Despite this longstanding interest, the neural representations of genitals are still poorly understood [6]. In somatosensory cortex specifically, many studies did not detect any cortical representation of genitals [7, 8 and 9]. Studies in humans debate whether genitals are represented displaced below the foot of the cortical body map [10, 11 and 12] or whether they are represented somatotopically [13, 14 and 15]. We wondered what a high-resolution mapping of genital representations might tell us about the sexual differentiation of the mammalian brain. We identified genital responses in rat somatosensory cortex in a region previously assigned as arm/leg cortex. Genital responses were more common in males than in females. Despite such response dimorphism, we observed a stunning anatomical monomorphism of cortical penis and clitoris input maps revealed by cytochrome-oxidase-staining of cortical layer 4. Genital representations were somatotopic and bilaterally symmetric, and their relative size increased markedly during puberty. Size, shape, and erect posture give the cortical penis representation a phallic appearance pointing to a role in sexually aroused states. Cortical genital neurons showed unusual multi-body-part responses and sexually dimorphic receptive fields. Specifically, genital neurons were co-activated by distant body regions, which are touched during mounting in the respective sex. Genital maps indicate a deep homology of penis and clitoris representations in line with a fundamentally bi-sexual layout [16] of the vertebrate brain.
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Juvenile male zebra finches memorize and learn to sing the song of a male caregiver, or "tutor", during a complex vocal learning process. Juveniles are highly motivated to interact socially with their tutor, and these interactions are required for effective vocal learning. It is currently unknown what neurological mechanisms underlie attraction to tutors, but social motivation and affiliation in this and other species may be mediated by oxytocin and related nonapeptides. Here, we used qPCR to quantify expression of oxytocin receptor (OTR) mRNA in the lateral septum, auditory forebrain, and regions of the song control system in zebra finches throughout post-hatch development and vocal learning. We found that zebra finches express OTR mRNA in these regions from post-hatch day 5 to adulthood, encompassing the entire period of auditory and sensorimotor learning. We also mapped the binding of 125 I-ornithine vasotocin, an oxytocin receptor antagonist that binds to oxytocin receptors in songbird brain, to understand the neuroanatomical distribution of oxytocin-like action during vocal development. This study provides the groundwork for the use of zebra finches as a model for understanding the mechanisms underlying social motivation and its role in vocal development.
Chapter
Nervous systems have evolved many features to ensure that the resources necessary for survival and reproduction are attractive. Because not all resources are valuable in all contexts, those features need to be plastic, in other words, the attractiveness or ‘incentive salience’ of some stimuli should change according to context. Courtship vocalizations, for example, have high incentive salience only during the breeding season, when approaching potential mates is adaptive. Female songbirds are attracted to male song only when reproductive hormones, such as estradiol, are high. In this chapter, the brain mechanisms by which estradiol changes the incentive salience of song are considered. First, estradiol may act directly on central auditory structures. Second, cells synthesizing dopamine, norepinephrine, and serotonin innervate the auditory pathway and are sensitive to estradiol, making them excellent candidates for mediating the effects of endocrine state on the perception of song. Third, the auditory forebrain of songbirds contains dense populations of oxytocin receptors, which in mammals play a clear role in social reward and are regulated by estradiol. Each of these neuromodulatory systems may prime auditory areas to respond differently to song depending on the bird’s reproductive condition. Seasonally breeding songbirds, for which attraction to song changes throughout the year, are ideal model systems for understanding how these neuromodulatory systems contribute to plasticity of behavioral responses to sound. Juvenile male songbirds, which seek out song in order to learn to sing, offer the opportunity to study how these systems contribute to social motivation during development.
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Oxytocin is important for social interactions and maternal behaviour. However, little is known about when, where and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behaviour in female mice by enhancing auditory cortical pup call responses. Retrieval behaviour required the left but not right auditory cortex, was accelerated by oxytocin in the left auditory cortex, and oxytocin receptors were preferentially expressed in the left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally precise excitatory and inhibitory responses in the left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing.
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Parents know the transformative nature of having and caring for a child. Among many mammals, giving birth leads from an aversion to infant stimuli to irresistible attraction. Here, we review the biological mechanisms governing this shift in parental motivation in mammals. Estrogen and progesterone prepare the uterus for embryo implantation and placental development. Prolactin stimulates milk production, whereas oxytocin initiates labor and triggers milk ejection during nursing. These same molecules, interacting with dopamine, also activate specific neural pathways to motivate parents to nurture, bond with, and protect their offspring. Parenting in turn shapes the neural development of the infant social brain. Recent work suggests that many of the principles governing parental behavior and its effect on infant development are conserved from rodent to humans.
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Previous investigations of parents' abilities to recognize the cries of their own babies have identified substantial and significant sex differences, with mothers showing greater correct recognition rates than fathers. Such sex differences in parenting abilities are common in non-human mammals and usually attributed to differential evolutionary pressures on male and female parental investment. However, in humans the traditional concept of 'maternal instinct' has received little empirical support and is incongruous given our evolutionary past as cooperative breeders. Here we use a controlled experimental design to show that both fathers and mothers can reliably and equally recognize their own baby from their cries, and that the only crucial factor affecting this ability is the amount of time spent by the parent with their own baby. These results highlight the importance of exposure and learning in the development of this ability, which may rely on shared auditory and cognitive abilities rather than sex-specific innate predispositions.
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Building on animal research, the past decade has witnessed a surge of interest in the effects of oxytocin on social cognition and prosocial behavior in humans. This work has generated considerable excitement about identifying the neurochemical underpinnings of sociality in humans, and discovering compounds to treat social functioning deficits. Inspection of the literature, however, reveals that the effects of oxytocin in the social domain are often weak and/or inconsistent. We propose that this literature can be informed by an interactionist approach in which the effects of oxytocin are constrained by features of situations and/or individuals. We show how this approach can improve understanding of extant research, suggest novel mechanisms through which oxytocin might operate, and refine predictions about oxytocin pharmacotherapy.
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The interplay between excitation and inhibition in the auditory cortex is crucial for the processing of acoustic stimuli. However, the precise role that inhibition plays in the distributed cortical encoding of natural vocalizations has not been well studied. We recorded single units (SUs) and local field potentials (LFPs) in the awake mouse auditory cortex while presenting pup isolation calls to animals that either do (mothers) or do not (virgins) recognize the sounds as behaviorally relevant. In both groups, we observed substantial call-evoked inhibition. However, in mothers this was earlier, longer, stronger, and more stereotyped compared to virgins. This difference was most apparent for recording sites tuned to tone frequencies lower than the pup calls' high-ultrasonic frequency range. We hypothesize that this auditory cortical inhibitory plasticity improves pup call detection in a relatively specific manner by increasing the contrast between call-evoked responses arising from high-ultrasonic and lateral frequency neural populations.
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Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities. OT treatment fully restores social recognition. Here we demonstrate that OT acts in the medial amygdala during the initial exposure to facilitate social recognition. OT given before, but not after, the initial encounter restores social recognition in OT knock-out mice. Using c-Fos immunoreactivity (Fos-IR) as a marker of neuronal activation in this initial encounter, we found similar neuronal activation in the wild-type (WT) and OT knock-out mouse in olfactory bulbs, piriform cortex, cortical amygdala, and the lateral septum. Wild-type, but not OT knock-out mice exhibited an induction of Fos-IR in the medial amygdala. Projections sites of the medial amygdala also failed to show a Fos-IR induction in the OT knock-out mice. OT knock-out, but not WT, mice showed dramatic increases in Fos-IR in the somatosensory cortex and the hippocampus, suggesting alternative processing of social cues in these animals. With site-specific injections of OT and an OT antagonist, we demonstrate that OT receptor activation in the medial amygdala is both necessary and sufficient for social recognition in the mouse.
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Human imaging studies have revealed that intranasal administration of the “prosocial” hormone oxytocin (OT) activates the frontal cortex, and this action of OT correlates with enhanced brain function in autism. Here, we report the discovery of a population of somatostatin (Sst)-positive, regular spiking interneurons that express the oxytocin receptor (OxtrINs). Silencing of OxtrINs in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice specifically during the sexually receptive phase of the estrous cycle. This sociosexual deficit was also present in mice in which the Oxtr gene was conditionally deleted from the mPFC and in control mice infused with an Oxtr antagonist. Our data demonstrate a gender-, cell type-, and state-specific role for OT/Oxtr signaling in the mPFC and identify a latent cortical circuit element that may modulate other complex social behaviors in response to OT.
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Background: Little is known about the regional brain basis of human maternal behavior. To understand this better, we have been examining brain activity in mothers listening to infant cries. Methods: We measured functional Magnetic Resonance Imaging brain activity in healthy, breastfeeding first-time mothers with young infants while they listened to infant cries, white noise control sounds, and a rest condition. Based on the thalamocingulate theory of maternal behavior and pilot work, we hypothesized that the cingulate, medial thalamus, medial prefrontal cortex, and right orbitofrontal cortex would display more activity with infant cries than with white noise (comparison 1) and would uniquely activate with the cries, meaning that these regions would display activity with cry minus rest but not with white noise minus rest (comparison 2). Results: In hypothesized regions, the group displayed more activity in the medial thalamus, medial prefrontal and right orbitofrontal cortices with both comparisons. The anterior and posterior cingulate cortex displayed more activity only with comparison 1. In non-hypothesized brain regions, several other structures thought important in rodent maternal behavior displayed activity with both comparisons including the midbrain, hypothalamus, dorsal and ventral striatum, and vicinity of the lateral septal region. Conclusions: Our results partially support our hypotheses and are generally consistent with neuroanatomical studies of rodent maternal behavior.