behavioral-tasks-for-examining-identity-recognition-in-mice

Behavioral Tasks for Examining Identity Recognition In Mice

Social animals, like rodents, are able to recognize and differentiate between the identity of familiar individuals. Recognizing the identity of familiar ...

McGill University

Douglas Research Centre

The hippocampus has been highly implicated in depression symptoms. Recent findings suggest that the expression and susceptibility of depression symptoms are related to the enhanced functioning of the hippocampus. We reasoned that hippocampal engrams, which represent ensembles of neurons with increased activity after memory formation, could underlie some contributions of the hippocampus to depression symptoms. Using the chronic social defeat stress model, we examined social defeat-related hippocampal engrams in mice that are either susceptible or resilient to the stressor.  mice were used to label social defeat-related hippocampal ensembles by LacZ. Engram cells correspond to ensembles that were reactivated by the same stressor. Compared with resilient and nonstressed control mice, susceptible mice exhibited a higher reactivation of social defeat-related LacZ-labeled cells (i.e., engram cells) in both the dorsal and ventral hippocampal CA1 regions. The density of CA1 engram cells correlated with the level of social avoidance. Using DREADD and optogenetic approaches to activate and inactivate social defeat-related CA1 engram cells enhanced and suppressed social avoidance, respectively. Increased engram cells in susceptible mice could not be found in the dentate gyrus. Susceptible mice exhibited more negative stimuli-related, but not neutral stimuli-related, CA1 engram cells than resilient mice in the dorsal hippocampus. Finally, chronic, but not a short and subthreshold, social defeat protocol was necessary to increase CA1 engram cell density. The susceptibility to chronic social defeat stress is regulated by hippocampal CA1 engrams for negative memory. Hippocampal negative memory engrams may underlie the vulnerability and expression of cognitive symptoms in depression. We provided evidence that negative memory hippocampal engrams contribute to the susceptibility to developing depression-related behavior after chronic social defeat stress. The activation of positive memory engrams has been shown to alleviate depression-related behaviors, while our findings reveal the pathological roles of negative memory engrams that could lead to those behaviors. Increased negative memory engrams could be a downstream effect of the reported high hippocampal activity in animal models and patients with depression. Unlike affective symptoms, we know much less about the cellular mechanisms of the cognitive symptoms of depression. Given the crucial roles of hippocampal engrams in memory formation, enhanced reactivation of negative memory engrams could be an important cellular mechanism that underlies the cognitive symptoms of depression.

Negative Memory Engrams in the Hippocampus Enhance the Susceptibility to Chronic Social Defeat Stress.

The 42nd Annual Meeting of the Canadian College of Neuropsychopharmacology.

While correlational studies suggest that lactation may confer a certain level of protection from mental illness, this benefit is not uniformly expressed in all women who choose to breastfeed. We propose here that the neuroendocrine "resetting" induced by lactation may predispose toward positive affect states in a subset of hormone-sensitive mothers, with hormone-gene and hormone-environment interactions determining the ultimate psychological outcome. We find evidence to suggest that higher secretion of prolactin/oxytocin as well as lower secretion of vasopression/androgens in lactating mothers may protect against postpartum depression and anxiety, decrease levels of irritability, and optimize stress responses. On the other hand, while the abrupt withdrawal of estradiol/progesterone in the immediate postpartum period tends to be associated with adverse psychological outcomes, the chronic suppression of estrogens/progestogens induced by lactation may have antidepressant and anxiolytic effects over time. Finally, the hypo-cortisolemic state seen in lactating mothers appears to be associated with improved stress reactivity and circadian rhythms. We also discuss hormone-gene and hormone-environment interactions likely to modulate any potential psychological benefits related to lactation and focus on those factors that are either easy to screen for or known to be modifiable. In sum, neuroendocrine alterations induced by lactation may play a key role in determining reproductive psychiatric risk in a subset of hormone-sensitive women. Using these neuroendocrine factors as an individualized index of risk can help in devising targeted programs to support these women in pursuing lactation or, for those not able or willing, accessing psychological interventions in a timely manner.

Neuroendocrine Effects of Lactation and Hormone-Gene-Environment Interactions.

A pertinent mechanism by which stress impacts learning and memory is through stress-induced plastic changes in glutamatergic transmission in the hippocampus. For instance, acute stress has been shown to alter the expression, binding, and function of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR). However, the consequences of chronic stress, which could lead to various stress-related brain disorders, on NMDAR function remain unclear. While most studies on NMDARs focused on these receptors in synapses (synaptic NMDARs or sNMDARs), emerging findings have revealed functional roles of NMDARs outside synapses (extrasynaptic NMDARs or exNMDARs) that are distinct from those of sNMDARs. Using a restraint stress paradigm in adult rats, the objective of the current study is to examine whether sNMDARs and exNMDARs in the hippocampus are differentially regulated by acute and chronic stress. We examined sNMDAR and exNMDAR function in dorsal CA1 hippocampal neurons from brain slices of adult rats that were acutely (1 episode) or chronically (21 daily episodes) stressed by restraint (30 min). We found that acute stress increases sNMDAR but suppresses exNMDAR function. Surprisingly, we only observed a reduction in exNMDAR function after chronic stress. Taken together, our findings suggest that sNMDARs and exNMDARs may be differentially regulated by acute and chronic stress. Most importantly, the observed suppression in exNMDAR function by both acute and chronic stress implies crucial but overlooked roles of hippocampal exNMDARs in stress-related disorders.

Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress.

We aim to clarify whether type and timing of mental health symptoms in early pregnancy distinctly contribute to maternal-fetal vascular function, independent from the psychotropic medications given to treat these conditions.

Maternal anxiety, depression and vascular function during pregnancy.

Understanding the individual variability that comes with the likelihood of developing stress-related psychopathologies is of paramount importance when addressing mechanisms of their neurobiology. This article focuses on the hippocampus as a region that is highly influenced by chronic stress exposure and that has strong ties to the development of related disorders, such as depression and post-traumatic stress disorder. We first outline three commonly used animal models that have been used to separate animals into susceptible and resilient cohorts. Next, we review molecular and functional hippocampal markers of susceptibility and resilience. We propose that the hippocampus plays a crucial role in the differences in the processing and storage of stress-related information in animals with different stress susceptibilities. These hippocampal markers not only help us attain a more comprehensive understanding of the various facets of stress-related pathophysiology, but also could be targeted for the development of new treatments.

The hippocampus in stress susceptibility and resilience: Reviewing molecular and functional markers.

As a crucial player in excitatory synaptic transmission, AMPA receptors (AMPARs) contribute to the formation, regulation, and expression of social behaviors. AMPAR modifications have been associated with naturalistic social behaviors, such as aggression, sociability, and social memory, but are also noted in brain diseases featuring impaired social behavior. Understanding the role of AMPARs in social behaviors is timely to reveal therapeutic targets for treating social impairment in disorders, such as autism spectrum disorder and schizophrenia. In this review, we will discuss the contribution of the molecular composition, function, and plasticity of AMPARs to social behaviors. The impact of targeting AMPARs in treating brain disorders will also be discussed.

Article	Year
Negative Memory Engrams in the Hippocampus Enhance the Susceptibility to Chronic Social Defeat Stress. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 31405928	2019
The 42nd Annual Meeting of the Canadian College of Neuropsychopharmacology. Journal of psychiatry & neuroscience : JPN\| PubMed ID: 31657536	2019
Neuroendocrine Effects of Lactation and Hormone-Gene-Environment Interactions. Molecular neurobiology\| PubMed ID: 31927723	2020
Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress. Frontiers in molecular neuroscience\| PubMed ID: 34690693	2021
Maternal anxiety, depression and vascular function during pregnancy. Journal of psychosomatic research\| PubMed ID: 35114604	2022
The hippocampus in stress susceptibility and resilience: Reviewing molecular and functional markers. Progress in neuro-psychopharmacology & biological psychiatry\| PubMed ID: 35842073	2022
Roles of AMPA receptors in social behaviors. Frontiers in synaptic neuroscience\| PubMed ID: 39056071	2024

Amanda Larosa

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