Social Isolation Induces Rac1-Dependent Forgetting of Social Memory

Liu, Yunlong; Lv, Li; Wang, Lianzhang; Zhong, Yi

doi:10.1016/j.celrep.2018.09.033

Cited by 56 publications

(59 citation statements)

References 61 publications

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“…These changes in the frontal cortex may be related to the memory deficits frequently observed in socially isolated animals [5,12,42]. Novel object recognition [5,6,8,42] and fear conditioning [10] show deficits after adolescent social isolation. Adolescent social isolation can also lead to low spatial learning and memory in the Morris water maze and poor working memory in the Y-maze [12].…”

Section: Discussionmentioning

confidence: 92%

“…Exposure to social stress or social isolation in adolescence is associated with alterations in glutamatergic and GABAergic transmission [5,17,18], myelin-related gene expression [19], structural connectivity and impaired plasticity [21]. These changes in the frontal cortex may be related to the memory deficits frequently observed in socially isolated animals [5,12,42]. Novel object recognition [5,6,8,42] and fear conditioning [10] show deficits after adolescent social isolation.…”

Section: Discussionmentioning

confidence: 99%

“…Object recognition memory was not impaired in group housed mice and neighbor housing returned object recognition memory to the levels observed in group housed mice. What remains unclear is if these memory deficits are a result of problems with memory consolidation or with enhanced forgetting [10,42]. Future studies are needed to address this question.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A Novel Neighbor Housing Environment Enhances Social Interaction and Rescues Cognitive Deficits from Social Isolation in Adolescence

Pais

Elmisurati

et al. 2019

Brain Sciences

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Adolescence is characterized by high levels of playful social interaction, cognitive development, and increased risk-taking behavior. Juvenile exposure to social isolation or social stress can reduce myelin content in the frontal cortex, alter neuronal excitability, and disrupt hypothalamic pituitary adrenal (HPA) axis function. As compared to group housed animals, social isolation increases anxiety-like phenotypes and reduces social and cognitive performance in adulthood. We designed a neighbor housing environment to alleviate issues related to social isolation that still allowed individual homecages. Neighbor housing consists of four standard mouse cages fused together with semi-permeable ports that allow visual, olfactory, and limited social contact between mice. Adolescent C57BL/6J males and females were group housed (4/cage), single housed (1/cage), or neighbor housed (4/complex). As adults, mice were tested for social, anxiety-like, and cognitive behaviors. Living in this neighbor environment reduced anxiety-like behavior in the social interaction task and in the light-dark task. It also rescued cognitive deficits from single housing in the novel object recognition task. These data suggest that neighbor housing may partially ameliorate the social anxiety and cognitive deficits induced by social isolation. These neighbor cage environments may serve as a conduit by which researchers can house mice in individual cages while still enabling limited social interactions to better model typical adolescent development.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Neighbor Housing Environment Enhances Social Interaction and Rescues Cognitive Deficits from Social Isolation in Adolescence

Pais

Elmisurati

et al. 2019

Brain Sciences

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“…This lack of social recognition memory is associated with a suppression of oxytocin‐dependent synaptic plasticity in the medial amygdala (MeA) following 7 days of isolation in rats . Impaired social recognition memory may also result from elevated hippocampal Rac1 (a small GTPase), which is evident in male mice isolated for 24 h or 7 days . Thus, isolation‐induced modifications to oxytocin signaling, in a pathway‐specific manner, may contribute to changes in both social motivation and social recognition memory.…”

Section: Homeostatic Response To Social Deficit: Engaging Social Motimentioning

confidence: 99%

Neural mechanisms of social homeostasis

Matthews

Tye

2019

Annals of the New York Academy of Sciences

153

101

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Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.

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“…Rac1, a small GTPase, can regulate the forgetting of memory (Shuai et al, 2010;Liu et al, 2018) and synaptic plasticity (Martinez and Tejada-Simon, 2011;Golden et al, 2013). Our recent investigations report that activation of hippocampal Rac1 promotes the forgetting of contextual fear memory in spaced learning rats, while inhibition of hippocampal Rac1 activity prevents the forgetting of contextual fear memory in massed learning rats (Jiang et al, 2016b).…”

Section: Introductionmentioning

confidence: 99%

Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors

Jiang

Wang

Huo

et al. 2020

Front. Mol. Neurosci.

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Spaced training is robustly superior to massed training, which is a well-documented phenomenon in humans and animals. However, the mechanisms underlying the spacing effect still remain unclear. We have reported previously that spacing training exerts memory-enhancing effects by inhibiting forgetting via decreasing hippocampal Rac1 activity. Here, using contextual fear conditioning in rat, we found that spaced but not massed training increased hippocampal 5-HT2A receptors' expression. Furthermore, hippocampal administration of 5-HT2A receptor antagonist MDL11939 before spaced training blocked the enhanced memory, while hippocampal administration of 5-HT2A receptor agonist TCB-2 before massed training promoted the memory. Moreover, MDL11939 activated hippocampal Rac1, while TCB-2 decreased hippocampal Rac1 activity in naïve rats. These results indicated the possibility of interaction between 5-HT2A receptors and Rac1, which was demonstrated by co-immunoprecipitation experiments. Our study first demonstrates that activation of hippocampal 5-HT2A is a mechanism underlying the spacing effect, and forgetting related molecular Rac1 is engaged in this process through interacting with 5-HT2A receptors, which suggest a promising strategy to modulate abnormal learning in cognitive disorders.

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Social Isolation Induces Rac1-Dependent Forgetting of Social Memory

Abstract: Highlights d Social isolation induces forgetting of social memory and Rac1 activation d Inhibition of Rac1 activity blocks isolation-induced forgetting of social memory d Resocialization reverses forgetting of social memory and Rac1 activation

Cited by 56 publications

References 61 publications

A Novel Neighbor Housing Environment Enhances Social Interaction and Rescues Cognitive Deficits from Social Isolation in Adolescence

A Novel Neighbor Housing Environment Enhances Social Interaction and Rescues Cognitive Deficits from Social Isolation in Adolescence

Neural mechanisms of social homeostasis

Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors

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