Sexually dimorphic neuronal responses to social isolation

Senst, Laura; Baimoukhametova, Dinara; Sterley, Toni-Lee; Bains, Jaideep S.

doi:10.7554/elife.18726

Cited by 81 publications

(61 citation statements)

References 32 publications

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“…CRF‐producing neurons are also widely distributed in extrahypothalamic regions, including the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), nucleus accumbens (NAc), and hippocampus, which have, likewise, been implicated in the behavioral and physiological responses to stress. Isolation of preadolescent female (but not male) mice for <24 h decreased the excitability of PVN CRF neurons in a glucocorticoid‐dependent manner . This finding may reflect glucocorticoid feedback–induced suppression of CRF activity.…”

Section: Homeostatic Response To Social Deficit: Promoting Hypervigilmentioning

confidence: 89%

Neural mechanisms of social homeostasis

Matthews

Tye

2019

Annals of the New York Academy of Sciences

155

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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Section: Homeostatic Response To Social Deficit: Promoting Hypervigilmentioning

confidence: 89%

Neural mechanisms of social homeostasis

Matthews

Tye

2019

Annals of the New York Academy of Sciences

155

101

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“…The current study is one of relatively few to use in vitro electrophysiological approaches to directly evaluate function of CRH neurons in PVN (e.g. see Senst et al, 2016; Wamsteeker Cusulin et al, 2013), and the first to do so after chronic salt-loading. It is interesting to note that prior work in rats has indicated that chronic variable stress (CVS) produces an increase in VGluT2 appositions to PVN CRH neurons without altering the number of GABAergic-immunoreactive boutons (Flak et al, 2009), suggesting the possibility that CVS and chronic salt have opposing physiological impact on excitation of CRH neurons.…”

Section: Discussionmentioning

confidence: 99%

Chronic salt-loading reduces basal excitatory input to CRH neurons in the paraventricular nucleus and accelerates recovery from restraint stress in male mice

Krause

Pati

Frazier

2017

Physiology & Behavior

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Neurons synthesizing corticotrophin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN) are activated during acute stress and act via the hypothalamic-pituitary-adrenal (HPA) axis to increase systemic levels of corticosterone (CORT). Recent data indicates that CRH neurons in the PVN are inhibited by acute salt-loading, and that this inhibition blunts the response to restraint stress as measured by increases in plasma CORT. The current study evaluates the effects of chronic rather than acute salt-loading on stress-induced activation of the HPA axis. Relative to euhydrated controls, chronic salt-loading over a 5-day period elevated plasma sodium and fluid intake without eliciting hypovolemia or substantial alterations in food intake or body weight. Chronic salt-loading also decreased expression of CRH mRNA in the anterior but not posterior portion of the PVN. Similarly, whole cell patch clamp recordings revealed that salt-loading effectively decreases spontaneous excitatory input to CRH neurons in the PVN without altering spontaneous inhibitory input. Generally consistent with these observations, chronic salt attenuated HPA axis activation as indicated by a significant reduction of plasma CORT during recovery from restraint stress.

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“…PVN CRH neurons initiate an endocrine cascade that increases circulating CORT. CORT has been shown to directly (Senst et al 2016) and indirectly (Di et al 2003;Wamsteeker et al 2010) decrease excitability of PVN CRH neurons, but the effects of CORT on GABA transmission are not clear. Reports indicate that CORT either decreases (Verkuyl et al 2004(Verkuyl et al , 2005 or has no effect (Wamsteeker Cusulin et al 2013) on synaptic I Phasic .…”

Section: Introductionmentioning

confidence: 99%

Balancing tonic and phasic inhibition in hypothalamic corticotropin‐releasing hormone neurons

Colmers

Bains

2018

The Journal of Physiology

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Corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) are integratory hubs that regulate the endocrine response to stress. GABA inputs provide a basal inhibitory tone that constrains this system and circulating glucocorticoids (CORT) are important feedback controllers of CRH output. Surprisingly little is known about the direct effects of CORT on GABA synapses in PVN. Here we used whole-cell patch clamp recordings from CRH neurons in mouse hypothalamic brain slices to examine the effects of CORT on synaptic and extrasynaptic GABA signalling. We show that GABA transporters (GATs) limit constitutive activation of presynaptic GABA receptors and ensure high release probability at GABA synapses. GATs in combination with GABA receptors also curtail extrasynaptic GABA R signalling. CORT has no effect on synaptic GABA signalling, but increases extrasynaptic GABA tone through upregulation of postsynaptic GABA receptors. These data show that efficient GABA clearance and autoinhibition control the balance between synaptic (phasic) and extrasynaptic (tonic) inhibition in PVN CRH neurons. This balance is shifted towards increased extrasynaptic inhibition by CORT.

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Sexually dimorphic neuronal responses to social isolation

Cited by 81 publications

References 32 publications

Neural mechanisms of social homeostasis

Neural mechanisms of social homeostasis

Chronic salt-loading reduces basal excitatory input to CRH neurons in the paraventricular nucleus and accelerates recovery from restraint stress in male mice

Balancing tonic and phasic inhibition in hypothalamic corticotropin‐releasing hormone neurons

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