Left brain cortical activity modulates stress effects on social behavior

Rhim

Journal of Neuroscience

et al. 2016

131

106

Although the medial prefrontal cortex (mPFC) is known to play a crucial role in rodent social behavior, little is known about mPFC neural correlates of social behavior. In the present study, we examined single-neuron activity in the mPFC of mice performing a modified version of the three-chamber test. We found that a subset of mPFC neurons elevate discharge rates when approaching a stranger mouse but not when approaching an inanimate object or an empty chamber. Our results reveal mPFC neural activity that is correlated with social approach behavior in a widely used social-interaction paradigm. These findings might be helpful for future investigations of mPFC neural processes underlying social interaction in health and disease.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced Neuronal Activity in the Medial Prefrontal Cortex during Social Approach Behavior

Rhim

Journal of Neuroscience

et al. 2016

131

106

“…This is in agreement with previous finding that the right but not the left ACC controls observational fear learning in mice (Kim et al, 2012). The brain heavily integrates not only external but also internal causes (Donaldson et al, 2015; Funamizu et al, 2016; Kohl et al, 2018; Larkum, 2013; Lee et al, 2014; R. X. Lee et al, 2015; Matias et al, 2017; Murugan et al, 2017; Remedios et al, 2017; Roome and Kuhn, 2018; Tononi et al, 2016; Zelikowsky et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…The medial prefrontal cortex (mPFC), which includes ACC and prelimbic cortex (PL) in mice, have been reported to exhibit both functional and physiological asymmetry between hemispheres. For examples, the right mPFC was reported to control the acquisition of stress during hazardous experiences while the left mPFC was found to play a dominant role in translating stress into social behavior (E. Lee et al, 2015). The effects of erythropoietin on inhibitory synaptic transmission in the left and right PL of mice were also found to be opposite (Dik et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Development of PTSD-like behavior in adult mice after observing an acute traumatic event

Stephens

Kühn

2018

Preprint

“…Thus, we selected two distinct manipulations that have been shown to exert antidepressant effects in both humans and rodent models.Deep brain stimulation (DBS) of subgenual cingulate cortex (Brodmann area 25, BA25) induces antidepressant effects in select clinical populations with depression [10,30]. Critically, direct stimulation of left IL_Cx (the rodent homologue of BA25) exhibits antidepressant-like effects in the cSDS model as 7 well [31]. To test the impact of left IL_Cx stimulation on Electome activity, we infected animals with a stabilized step-function opsin (SSFO, AAV-CaMKII-SSFO) in IL_Cx (Fig.…”

mentioning

confidence: 99%

A convergent depression vulnerability pathway encoded by emergent spatiotemporal dynamics

Hultman

Ulrich

et al. 2017

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 network level. Here we use machine learning to integrate LFP activity acquired concurrently from seven cortical and subcortical brain regions into an analytical model that predicts the emergence of depression-related behavioral dysfunction across individual mice subjected to chronic social defeat stress. We uncover a spatiotemporal dynamic network in which activity originates in prefrontal cortex (PFC) and nucleus accumbens (NAc, ventral striatum), relays through amygdala and ventral tegmental area (VTA), and converges in ventral hippocampus (VHip). The activity of this network correlates with acute threat responses and brain-wide cellular firing, and it is enhanced in three independent molecular-, physiological-, and behavioral-based models of depression vulnerability. Finally, we use two antidepressant manipulations to demonstrate that this vulnerability network is biologically distinct from the networks that signal behavioral dysfunction after stress. Thus, corticostriatal to VHip-directed spatiotemporal dynamics organized at the network level are a novel convergent depression vulnerability pathway. Main TextMajor depressive disorder is the leading cause of disability in the world [1]. While stress contributes to the onset of depression [2,3], only a fraction of individuals that experience stressful events develop behavioral pathology. Multiple factors including childhood trauma and alterations in several molecular pathways have been shown to increase disease risk [3,4]; nevertheless, the neural pathways on which these factors converge to yield subthreshold changes that render individuals vulnerable to stress are unknown. Knowledge of these neural pathways would facilitate the development of novel diagnostic technologies that stratify disease risk as well as preventative therapeutics to reverse neural circuit endophenotypes that mediate vulnerability to depression. To achieve this aim it is essential to distinguish the neural alterations that confer vulnerability to depression from those that accompany the emergence of behavioral dysfunction.Chronic social defeat stress (cSDS) is a widely validated pre-clinical model of depression [5][6][7]. In this paradigm, test mice are repeatedly exposed to larger aggressive CD1 mice. At the end of these exposures, test mice develop a depression-like behavioral state characterized by social avoidance, anhedonia-and anxiety-like behavior, and sleep/circadian dysregulation [6,7]. Critically, only ~60% of C57 mice subjected to this paradigm exhibit susceptibility to developing this stress-induced syndrome. While the remaining ~40% of mice subjected to cSDS exhibit resilience [6], susceptible and resilient mice experience the...