Rosemary C Bagot

Rosemary C Bagot
McGill University | McGill · Department of Psychology

PhD

About

78
Publications
17,479
Reads
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5,418
Citations
Additional affiliations
September 2011 - present
Icahn School of Medicine at Mount Sinai
Position
  • PostDoc Position
Description
  • I study synaptic and transcriptional plasticity in depression. Techniques include in vivo optogenetics, in vitro optogenetic electrophysiology, next-generation sequencing and pathway- specific manipulation of gene expression.
Education
September 2004 - August 2011
McGill University
Field of study
  • Neuroscience
February 1999 - November 2002
UNSW Sydney
Field of study
  • Psychology

Publications

Publications (78)
Article
Background Social experiences influence susceptibility to substance use disorder. The adolescent period is associated with the development of social reward and is exceptionally sensitive to disruptions to reward-associated behaviors by social experience. Social isolation during adolescence alters anxiety- and reward-related behaviors in adult males...
Article
Making decisions is fundamental to how we navigate, survive, and thrive in our environment. The quality of information used to support decisions is rarely perfect. Many decisions are made under conditions of uncertainty, arising from ambiguous or conflicting information. Conflict and ambiguity, though conceptually distinct, both generate uncertaint...
Article
Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat s...
Article
Wang et al. (2021) characterize the molecular, cellular, and circuit-level role of Oligophrenin-1 in prefrontal parvalbumin interneurons, demonstrating that loss of Ophn1 function in these neurons is a mechanism for increased susceptibility to stress in intellectual disability caused by OPHN1 mutations.
Article
Women are twice as likely to experience depression than men, yet until recently, pre-clinical studies in rodents have focused almost exclusively on males. As interest in sex differences and sex-specific mechanisms of stress susceptibility increases, chronic stress models for inducing depression-relevant behavioral and physiological changes in male...
Article
Background Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental disorders later in life. The impact of gestational timing of MIA-exposure on downstream development remains unclear. Methods We characterized neurodevelopmental trajectories of mice exposed to viral mimetic, polyinosinic:polycytidylic acid (pol...
Article
Background Sex differences in addiction have been described in humans and animal models. A key factor that influences addiction in both males and females is adolescent experience. Adolescence is associated with higher vulnerability to substance use disorders, and male rodents subjected to adolescent social isolation stress (SI) form stronger prefer...
Preprint
Full-text available
Prenatal maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders. How gestational timing of MIA-exposure differentially impacts downstream development remains unclear. Here, we characterize neurodevelopmental trajectories of mice exposed to MIA induced by poly I:C either early (gestational day [GD]9) or late (GD17) in ges...
Article
Background Reinforcement learning (RL) and win stay/lose shift model accounts of decision making are both widely used to describe how individuals learn about and interact with rewarding environments. Though mutually informative, these accounts are often conceptualized as independent processes and so the potential relationships between win stay/lose...
Article
Full-text available
Background Stress is a major risk factor for depression, but not everyone responds to stress the same way. Identifying why certain individuals are more susceptible is essential for targeted treatment and prevention. In rodents, nucleus accumbens (NAc) afferents from the ventral hippocampus (vHIP) are implicated in stress-induced susceptibility but...
Preprint
Adolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-relate...
Article
Full-text available
Abuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmenta...
Article
Full-text available
Understanding the transcriptional changes that are engaged in stress resilience may reveal novel antidepressant targets. Here we use gene co-expression analysis of RNA-sequencing data from brains of resilient mice to identify a gene network that is unique to resilience. Zfp189, which encodes a previously unstudied zinc finger protein, is the highes...
Preprint
Abuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmenta...
Article
Full-text available
The transcription factor ΔFosB has been proposed as a molecular switch for the transition from casual, volitional drug use into a chronically addicted state, but the upstream regulatory mechanisms governing ΔFosB expression are incompletely understood. In this study, we find a novel regulatory role for the transcription factor E2F3, recently implic...
Article
Full-text available
Epidemiological evidence identifies early life adversity as a significant risk factor for the development of mood disorders. Much evidence points to the role of early life experience in susceptibility and, to a lesser extent, resilience, to stress in adulthood. While many models of these phenomena exist in the literature, results are often conflict...
Article
Drug abuse is a multifaceted disorder that involves maladaptive decision making. Long-lasting changes in the addicted brain are mediated by a complex circuit of brain reward regions. The prefrontal cortex (PFC) is one region in which chronic drug exposure changes expression and function of upstream transcriptional regulators to alter drug responses...
Article
The advent of optogenetics and chemogenetics has revolutionized the study of neural circuit mechanisms of behavioral dysregulation in psychiatric disease. These powerful technologies allow manipulation of specific neurons to determine causal relationships between neuronal activity and behavior. Optogenetic tools have been key to mapping the circuit...
Preprint
Stress resilience involves numerous brain-wide transcriptional changes. Determining the organization and orchestration of these transcriptional events may reveal novel antidepressant targets, but this remains unexplored. Here, we characterize the resilient transcriptome with co-expression analysis and identify a single transcriptionally-active uniq...
Article
Full-text available
The role of somatostatin interneurons in nucleus accumbens (NAc), a key brain reward region, remains poorly understood due to the fact that these cells account for < 1% of NAc neurons. Here, we use optogenetics, electrophysiology, and RNA-sequencing to characterize the transcriptome and functioning of NAc somatostatin interneurons after repeated ex...
Article
Background Global changes in gene expression underlying circuit and behavioral dysregulation associated with cocaine addiction remain incompletely understood. Here, we show how a history of cocaine self-administration (SA) “re-programs” transcriptome-wide responses throughout the brain’s reward circuitry at baseline and in response to context and/o...
Article
Full-text available
Most people exposed to stress do not develop depression. Animal models have shown that stress resilience is an active state that requires broad transcriptional adaptations, but how this homeostatic process is regulated remains poorly understood. In this study, we analyze upstream regulators of genes differentially expressed after chronic social def...
Article
Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional pathology. Using machin...
Article
Background: Lasting changes in gene expression in brain reward regions, including nucleus accumbens (NAc), contribute to persistent functional changes in the addicted brain. We and others have demonstrated that altered expression of several candidate transcription factors in NAc regulates drug responses. A recent large-scale genome-wide study from...
Preprint
Fluctuations in brain local field potential (LFP) oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these LFP oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors would provide fundamental insights into how the brain signals emotional processes at the n...
Article
Early life stress increases risk for depression. Here we establish a "two-hit" stress model in mice wherein stress at a specific postnatal period increases susceptibility to adult social defeat stress and causes long-lasting transcriptional alterations that prime the ventral tegmental area (VTA)-a brain reward region-to be in a depression-like stat...
Article
Recognizing why chronic stress causes only a subset of individuals to become depressed is critical to understanding depression on a basic level and, also to developing treatments that increase resilience. Stress-induced alterations in the activity of reward-related brain regions, such as the nucleus accumbens (NAc), are linked to the pathophysiolog...
Article
The nucleus accumbens (NAc) is a primary brain reward region composed predominantly of medium spiny neurons (MSNs). In response to early withdrawal from repeated cocaine administration, de novo dendritic spine formation occurs in NAc MSNs. Much evidence indicates that this new spine formation facilitates the rewarding properties of cocaine. Early w...
Article
Full-text available
PHF8 is a histone demethylase with specificity for repressive modifications. While mutations of PHF8 have been associated with cognitive defects and cleft lip/palate, its role in mammalian development and physiology remains unexplored. Here, we have generated a Phf8 knockout allele in mice to examine the consequences of Phf8 loss for development an...
Data
Supplementary Figures, Supplementary Tables.
Article
Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain r...
Article
Full-text available
BACKGROUD: Variations in the expression of the Netrin-1 guidance cue receptor DCC (Deleted in colorectal cancer) appear to confer resilience or susceptibility to psychopathologies involving prefrontal cortex (PFC) dysfunction. METHODS: Using postmortem brain tissue, mouse models of defeat stress, and in vitro analysis, we assessed microRNA (miRNA)...
Article
Full-text available
Human major depressive disorder (MDD), along with related mood disorders, is among the world's greatest public health concerns; however, its pathophysiology remains poorly understood. Persistent changes in gene expression are known to promote physiological aberrations implicated in MDD. More recently, histone mechanisms affecting cell type- and reg...
Article
Full-text available
Examining transcriptional regulation by antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Given the heterogeneity of treatment response in human populations, examining both treatment...
Article
Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain r...
Article
Dendritic spines are the sites of most excitatory synapses in the CNS, and opposing alterations in the synaptic structure of medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a primary brain reward region, are seen at early versus late time points after cocaine administration. Here we investigate the time-dependent molecular and biochemic...
Article
Full-text available
The reinforcing and rewarding properties of cocaine are attributed to its ability to increase dopaminergic transmission in nucleus accumbens (NAc). This action reinforces drug taking and seeking and leads to potent and long-lasting associations between the rewarding effects of the drug and the cues associated with its availability. The inability to...
Article
Full-text available
Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin stru...
Article
Background We examined the neurobiological mechanisms underlying stress susceptibility using structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to determine neuroanatomical differences between stress-susceptible and resilient mice. We also examined synchronized anatomical differences between brain regions to gain insight...
Article
Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation-associated histone dynamics in the regulation of activity-dependent tran...
Article
Full-text available
Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vH...
Article
Full-text available
Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vH...
Article
Brain-derived neurotrophic factor (BDNF) has a crucial role in modulating neural and behavioral plasticity to drugs of abuse. We found a persistent downregulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which was mediated by specific epigenetic modifications at the corresponding B...
Article
Variations in early life maternal care modulate hippocampal development to program distinct emotional-cognitive phenotypes that persist into adulthood. Adult rat offspring that received low compared to high levels of maternal licking and grooming (low LG offspring) in early postnatal life show reduced long term potentiation (LTP) and impaired hippo...
Article
Full-text available
β-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice β-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect med...
Article
Full-text available
Psychiatric disorders are complex multifactorial disorders involving chronic alterations in neural circuit structure and function. While genetic factors play a role in the etiology of disorders such as depression, addiction, and schizophrenia, relatively high rates of discordance among identical twins clearly point to the importance of additional f...
Article
Full-text available
Stable changes in neuronal gene expression have been studied as mediators of addicted states. Of particular interest is the transcription factor ΔFosB, a truncated and stable FosB gene product whose expression in nucleus accumbens (NAc), a key reward region, is induced by chronic exposure to virtually all drugs of abuse and regulates their psychomo...
Article
Psychiatric disorders are complex multifactorial illnesses involving chronic alterations in neural circuit structure and function. While genetic factors are important in the etiology of disorders such as depression and addiction, relatively high rates of discordance among identical twins clearly indicate the importance of additional mechanisms. Env...
Article
Full-text available
Decreased medial prefrontal cortex (mPFC) neuronal activity is associated with social defeat-induced depression- and anxiety-like behaviors in mice. However, the molecular mechanisms underlying the decreased mPFC activity and its prodepressant role remain unknown. We show here that induction of the transcription factor ΔFosB in mPFC, specifically i...
Article
Full-text available
Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has recently been implicated in transcriptional, morphological and behavioral responses to chronic cocaine administration. Here, using a ribosomal affinity purification approach, we found that G9a repression by cocaine occurred in both Drd1-expressing (striatonigral) and Drd2-ex...
Article
Full-text available
Regulator of G protein signalling 9-2 (Rgs9-2) modulates the actions of a wide range of CNS acting drugs by controlling signal transduction of several GPCRs in the striatum. RGS9-2 acts via a complex mechanism which involves interactions with Gα subunits, the Gβ5 protein, and the adaptor protein R7BP. Our recent work identified Rgs9-2 complexes in...
Article
Full-text available
The transcription factor, ΔFosB, is robustly and persistently induced in striatum by several chronic stimuli, such as drugs of abuse, antipsychotic drugs, natural rewards, and stress. However, very few studies have examined the degree of ΔFosB induction in the two striatal medium spiny neuron (MSN) subtypes. We make use of fluorescent reporter BAC...
Data
Although NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) of glutamatergic transmission are candidate mechanisms for long-term spatial memory, the precise contributions of LTP and LTD remain poorly understood. Here, we report that LTP and LTD in the hippocampal CA1 region of freely moving adult rats were p...
Article
Variations in maternal care in the rat affect hippocampal morphology and function as well as performance on hippocampal-dependent tests of learning and memory in the offspring. Preliminary genome-wide analyses of gene transcription and DNA methylation of the molecular basis for such maternal effects suggested differences in the epigenetic state and...
Article
Full-text available
The influence of developmental nicotine exposure on the brain represents an important health topic in light of the popularity of nicotine replacement therapy (NRT) as a smoking cessation method during pregnancy. In this study, we used a model of NRT during pregnancy and breastfeeding to explore the consequences of chronic developmental nicotine exp...