Anita E Autry

Albert Einstein College of Medicine | AECOM · Department of Molecular and Cell Biology

Historically associated with aversion, the lateral habenula has a poorly characterized role in parenting. In this issue of Neuron, Lecca and colleagues1 show that these seemingly opposing roles converge in a subnucleus where aversion to pup cries may drive motivation for caregiving.

Infant avoidance and aggression are promoted by activation of the Urocortin-3 expressing neurons of the perifornical area of hypothalamus (PeFAUcn3) in male and female mice. PeFAUcn3 neurons have been implicated in stress, and stress is known to reduce maternal behavior. We asked how chronic restraint stress (CRS) affects infant-directed behavior i...

Depression is a prevalent mental health disorder and is the number one cause of disability worldwide. Risk factors for depression include genetic predisposition and stressful life events, and depression is twice as prevalent in women compared to men. Both clinical and preclinical research have implicated a critical role for brain-derived neurotroph...

The amygdalohippocampal transition area (AHi) has emerged as a critical nucleus of sociosexual behaviors such as mating, parenting, and aggression. The AHi has been overlooked in rodent and human amygdala studies until recently. The AHi is hypothesized to play a role in metabolic and cognitive functions as well as social behaviors based on its conn...

Infant avoidance and aggression are promoted by activation of the Urocortin-3 expressing neurons of the perifornical area of hypothalamus (PeFA Ucn3 ) in male and female mice. PeFA Ucn3 neurons have been implicated in stress, and stress is known to reduce maternal behavior. We asked how chronic restraint stress (CRS) affects infant-directed behavio...

Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, has been employed clinically as an intravenous anesthetic since the 1970s. More recently, ketamine has received attention for its rapid antidepressant effects and is actively being explored as a treatment for a wide range of neuropsychiatric syndromes. In model systems, k...

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 ( Ucn3 )-expressing neurons in the hypothalamic perifornical area (PeFA Ucn3 ) are activated during i...

The rapidly acting antidepressants ketamine and scopolamine exert behavioral effects that can last from several days to more than a week in some patients. The molecular mechanisms underlying the maintenance of these antidepressant effects are unknown. Here we show that methyl-CpG-binding protein 2 (MeCP2) phosphorylation at Ser421 (pMeCP2) is essen...

Brain-derived neurotrophic factor (BDNF) is a key molecule involved in various aspects of neuronal circuit development and function. In this chapter, we will first discuss the complex transcriptional and translational regulation of BDNF, its secretion, and receptor-mediated actions at pre- and postsynaptic sites. Next, we will cover how those funct...

Mammals invest considerable resources in protecting and nurturing young offspring. However, under certain physiological and environmental conditions, animals neglect or attack young conspecifics. Males in some species attack unfamiliar infants to gain reproductive advantage and females kill or neglect their young during stressful circumstances such...

Parenting is essential for the survival and wellbeing of mammalian offspring. However, we lack a circuit-level understanding of how distinct components of this behaviour are coordinated. Here we investigate how galanin-expressing neurons in the medial preoptic area (MPOAGal) of the hypothalamus coordinate motor, motivational, hormonal and social as...

Supplementary Video 2. Barrier crossing evoked by MPOAGal→VTA activation Optogenetic activation of MPOAGal→VTA projections in a virgin Gal::Cre female evokes barrier crossing in a task assessing motivation to interact with pups. Photostimulation period indicated by white dot.

Supplementary Video 1. MPOAGal population activity during parenting Pan-MPOAGal fibre photometry recording in a mother. While (1) no change in signal is visible during interactions with a food object (sniffing, retrieving of cracker), (2) sniffing pups in a wire mesh cage results in modest, and (3) sniffing and grooming of pups in the nest in stron...

Social interactions are essential for animals to reproduce, defend their territory, and raise their young. The conserved nature of social behaviors across animal species suggests that the neural pathways underlying the motivation for, and the execution of, specific social responses are also maintained. Modern tools of neuroscience have offered new...

Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, tropomyosin receptor kinase B (TrkB), play important roles in neural plasticity and are required for antidepressant efficacy. Studies examining the role of BDNF-TrkB signaling in depression and antidepressant efficacy have largely focused on the limbic system leaving it unclea...

DNA methylation has been shown to impact certain forms of synaptic and behavioral plasticity that have been implicated in the development in psychiatric disorders. DNA methylation is catalyzed by DNA methyltransferase (DNMT) enzymes that continue to be expressed in postmitotic neurons in the forebrain. Using a conditional forebrain knockout of DNMT...

Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity a...

Epigenetic processes are well-known to play critical roles in learning and memory. Among epigenetic processes, accumulating data suggests that DNA methylation in particular is a critical determinant of learning and memory. In vitro data have suggested that DNA methyltransferase inhibitors can trigger DNA demethylation and subsequent gene expression...

Ketamine is a N-methyl-D-aspartate receptor (NMDAR) antagonist that produces rapid antidepressant responses in individuals with major depressive disorder. The antidepressant action of ketamine has been linked to blocking NMDAR activation at rest, which inhibits eukaryotic elongation factor 2 kinase leading to desuppression of protein synthesis and...

Mice display robust, stereotyped behaviours towards pups: virgin males typically attack pups, whereas virgin females and sexually experienced males and females display parental care. Here we show that virgin males genetically impaired in vomeronasal sensing do not attack pups and are parental. Furthermore, we uncover a subset of galanin-expressing...

The impact of spontaneous neurotransmission on neuronal plasticity remains poorly understood. Here, we show that acute suppression of spontaneous NMDA receptor-mediated (NMDAR-mediated) neurotransmission potentiates synaptic responses in the CA1 regions of rat and mouse hippocampus. This potentiation requires protein synthesis, brain-derived neurot...

Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytos...

Brain derived neurotrophic factor (BDNF) is the most prevalent growth factor in the central nervous system (CNS). It is essential for the development of the CNS and for neuronal plasticity. Because BDNF plays a crucial role in development and plasticity of the brain, it is widely implicated in psychiatric diseases. This review provides a summary of...

Rett syndrome and MECP2 duplication syndrome are neurodevelopmental disorders that arise from loss-of-function and gain-of-function alterations in methyl-CpG binding protein 2 (MeCP2) expression, respectively. Although there have been studies examining MeCP2 loss of function in animal models, there is limited information on MeCP2 overexpression in...

Major depressive disorder (MDD) is known to have a significant genetic component and is twice as prevalent in women as in men. However, little is known concerning the biological underpinnings of the relationship of gender to MDD. Recent data suggest that brain-derived neurotrophic factor (BDNF) is essential for normal depression behaviour and antid...

Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear. Depressed patients report the alle...

Major depression and suicide, which is its most severe outcome, are common problems that represent a major burden in our society. The relationship among early life adversity, depression, and suicide has already been well demonstrated, however, the molecular mechanisms mediating this relationship still remain poorly understood. From rat studies, we...

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that results from loss of function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Using viral-mediated basolateral amygdala (BLA)-specific deletion of Mecp2 in mice, we show that intact Mecp2 function is required for normal anxiety behavior as well as some types of learning...

Major depressive disorder is a leading debilitating disease known to occur at a two-fold higher rate in women than in men. The neurotrophic hypothesis of depression suggests that loss of brain-derived neurotrophic factor (BDNF) may increase susceptibility for depression-like behavior, although direct evidence is lacking. Using the chronic unpredict...

Brain-derived neurotrophic factor (BDNF) plays an important role in neural plasticity in the adult nervous system and has been suggested as a target gene for antidepressant treatment. The neurotrophic hypothesis of depression suggests that loss of BDNF from the hippocampus contributes to an increased vulnerability for depression, whereas upregulati...

In the rat hippocampus, the predominate glutamate transporters are GLT-1 and its recently identified isoform, GLT-1b. Chronic restraint stress increases GLT-1b expression throughout the hippocampus while more selectively increasing GLT-1 expression in the CA3 region. These studies suggest that GLT-1b expression is regulated by stress levels of gluc...