Grin1 deletion in CRF neurons sex-dependently enhances fear, sociability, and social stress responsivity

Gilman, T. Lee; DaMert, Jeffrey P.; Meduri, Jeremy D.; Jasnow, Aaron M.

doi:10.1016/j.psyneuen.2015.04.010

Cited by 22 publications

(16 citation statements)

References 69 publications

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“…First, CRF-producing neurons are regulated by different types of receptors [111]. Moreover, within CRF neurons, expression of CRF is reported to be higher in females than males in some brain regions, an effect that can overcome the ability of CRFBP to buffer the effects of CRF on anxiety in females [102].…”

Section: Discussionmentioning

confidence: 99%

“…These mice display increased fear expression and social withdrawal if they are male [111,112]. However, female mice are unaffected by this loss of NMDA receptor function in CRF neurons [111]. Thus, glutamatergic regulation of CRF neurons via NMDA receptors appears sex-specific.…”

Section: Sex Differences In Crf Expression and The Regulation Of Crf mentioning

confidence: 98%

“…CRF neurons express NMDA receptors, suggesting glutamatergic regulation of these cells [109]. Knocking out Grin1 subunits of the NMDA receptor results in a loss of NMDA function, and mice genetically modified so that Grin1 is deleted specifically from their CRF-containing neurons have been produced [110][111][112]. These mice display increased fear expression and social withdrawal if they are male [111,112].…”

Section: Sex Differences In Crf Expression and The Regulation Of Crf mentioning

confidence: 99%

“…Knocking out Grin1 subunits of the NMDA receptor results in a loss of NMDA function, and mice genetically modified so that Grin1 is deleted specifically from their CRF-containing neurons have been produced [110][111][112]. These mice display increased fear expression and social withdrawal if they are male [111,112]. However, female mice are unaffected by this loss of NMDA receptor function in CRF neurons [111].…”

Section: Sex Differences In Crf Expression and The Regulation Of Crf mentioning

confidence: 99%

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Sex differences in stress responses: a critical role for corticotropin-releasing factor

2018

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Rates of post-traumatic stress disorder, panic disorder, and major depression are higher in women than in men. Another shared feature of these disorders is that dysregulation of the stress neuropeptide, corticotropin-releasing factor (CRF), is thought to contribute to their pathophysiology. Therefore, sex differences in responses to CRF could contribute to this sex bias in disease prevalence. Here, we review emerging data from non-human animal models that reveal extensive sex differences in CRF functions ranging from its presynaptic regulation to its postsynaptic efficacy. Specifically, detailed are sex differences in the regulation of CRF-containing neurons and the amount of CRF that they produce. We also describe sex differences in CRF receptor expression, distribution, trafficking, and signaling. Finally, we highlight sex differences in the processes that mitigate the effects of CRF. In most cases, the identified sex differences can lead to increased stress sensitivity in females. Thus, the relevance of these differences for the increased risk of depression and anxiety disorders in women compared to men is also discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Sex Differences In Crf Expression and The Regulation Of Crf mentioning

confidence: 98%

Section: Sex Differences In Crf Expression and The Regulation Of Crf mentioning

confidence: 99%

Section: Sex Differences In Crf Expression and The Regulation Of Crf mentioning

confidence: 99%

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Sex differences in stress responses: a critical role for corticotropin-releasing factor

2018

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“…However, increased CeL activity associated with generalization might be cell‐type specific. Mice with precise cell‐specific ablation of NMDA receptor function exclusively in corticotropin releasing factor (CRF)‐expressing neurons, which are localized to the CeL, show generalized responding to CS – cues in fear discrimination tasks (Gilman et al, ). These data suggest that specificity of fear responses may be partially regulated by changes in activity within the inhibitory neural circuitry of the CeA.…”

Section: Cued Fear Generalizationmentioning

confidence: 99%

Perspectives on fear generalization and its implications for emotional disorders

Jasnow

Lynch

Gilman

et al. 2016

J of Neuroscience Research

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Although generalization to conditioned stimuli is not a new phenomenon, renewed interest in understanding its biological underpinning has stemmed from its association with a number of anxiety disorders. Generalization as it relates to fear processing is a temporally dynamic process in which animals, including humans, display fear in response to similar yet distinct cues or contexts as the time between training and testing increases. This Review surveys the literature on contextual fear generalization and its relation to several views of memory, including systems consolidation, forgetting, and transformation hypothesis, which differentially implicate roles of the hippocampus and neocortex in memory consolidation and retrieval. We discuss recent evidence on the neurobiological mechanisms contributing to the increase in fear generalization over time and how generalized responding may be modulated by acquisition, consolidation, and retrieval mechanisms. Whereas clinical perspectives of generalization emphasize a lack of fear inhibition to CS cues or fear toward intermediate CS cues, the time-dependent nature of generalization and its relation to traditional views on memory consolidation and retrieval are often overlooked. Understanding the time-dependent increase in fear generalization has important implications not only for understanding how generalization contributes to anxiety disorders but also for understanding basic long-term memory function. © 2016 Wiley Periodicals, Inc.

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Gender Differences in Posttraumatic Stress Disorder

Villamor-García

Adana

2019

Psychopathology in Women

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Grin1 deletion in CRF neurons sex-dependently enhances fear, sociability, and social stress responsivity

Cited by 22 publications

References 69 publications

Sex differences in stress responses: a critical role for corticotropin-releasing factor

Sex differences in stress responses: a critical role for corticotropin-releasing factor

Perspectives on fear generalization and its implications for emotional disorders

Gender Differences in Posttraumatic Stress Disorder

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