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Grossman, Y. S.

Publications and source records attributed to Grossman, Y. S..

2 recordsLinked to original sources

Brain-wide oscillatory network selectively encodes aggression

Aggression is a psychological state characterized by intent to harm oneself or others, and often manifests as hostile, harmful, or violent action. Social aggression can aid an organism in securing access to resources1,2, or it can impair group function and survival in behavioral pathology3-5. Since many brain regions contribute to multiple social behaviors6-8, expanded knowledge of how the brain distinguishes between social states would enable the development of interventions that suppress violent action, while leaving other social behaviors intact. Here we showed that a murine aggressive internal state is encoded by a widespread network. This network is organized by prominent and synchronized theta (4-11 Hz) and beta (14-30 Hz) oscillations that relay through the medial prefrontal cortex, and couples to widespread cellular firing. Strikingly, network activity during social isolation was found to encode the trait aggressiveness of mice, and causal cellular manipulations known to impact aggression were found to modulate the networks activity. We next established that this network mediates aggression using closed-loop stimulation of medial prefrontal cortex and causal mediation analysis. Finally, we deployed Long-term integration of Circuits using connexins (LinCx) to selectively edit a key circuit within the network from the medial prefrontal cortex to nucleus accumbens. Editing this circuit chronically suppressed violent action while leaving non-aggressive social behavior intact.

neuroscience↗

Prelimbic-amygdala overexcitability mediates trait vulnerability in a novel mouse model of acute social defeat stress

BACKGROUNDDepression is a debilitating neuropsychiatric disorder with 20% lifetime prevalence in the developed world but only approximately half of afflicted individuals respond to currently available therapies. While there is growing understanding of the neurobiological underpinnings of the depressed brain, much less is known about the preexisting circuitry leading to selective vulnerability versus resilience. Elucidating these networks could lead to novel preventative approaches. METHODSWe developed a model of acute social defeat stress (ASDS) that allows classification of male mice into "susceptible" (socially avoidant) versus "resilient" (expressing control-level social approach) one hour after exposure to six minutes of social stress. Using circuit tracing and high-resolution confocal imaging, we explored differences in activation and dendritic spine density and morphology in the prelimbic to basolateral amygdala (PL[->]BLA) circuit in resilient versus susceptible mice. To test the functional relevance of identified structure/function differences to divergent behavioral responses, we used an intersectional chemogenetic approach to inhibit the PL[->]BLA circuit during or prior to ASDS. RESULTSSusceptible mice had greater PL[->]BLA recruitment during ASDS and activated PL[->]BLA neurons from susceptible mice had more and larger mushroom spines compared to resilient mice. Inhibition of the PL[->]BLA circuit led to a population shift towards resilience. CONCLUSIONPreexisting PL[->]BLA structure/function differences mediate divergent behavioral responses to ASDS in male mice. These results support the PL[->]BLA circuit as a biomarker of trait vulnerability and potential target for prevention of stress-induced psychopathology.

neuroscience↗