Developmental Shifts in Amygdala Activity during a High Social Drive State

Abstract

Amygdala abnormalities characterize several psychiatric disorders with prominent social deficits and often emerge during adolescence. The basolateral amygdala (BLA) bidirectionally modulates social behavior and has increased sensitivity during adolescence. We tested how an environmentally-driven social state is regulated by the BLA in adults and adolescent male rats. We found that a high social drive state caused by brief social isolation increases age-specific social behaviors and increased BLA neuronal activity. Chemogenetic inactivation of BLA decreased the effect of high social drive on social engagement. High social drive preferentially enhanced BLA activity during social engagement; however, the effect of social opportunity on BLA activity was greater during adolescence. While this identifies a substrate underlying age differences in social drive, we then determined that high social drive increased BLA NMDA GluN2B expression and sensitivity to antagonism increased with age. Further, the effect of a high social drive state on BLA activity during social engagement was diminished by GluN2B blockade in an age-dependent manner. These results demonstrate the necessity of the BLA for environmentally driven social behavior, its sensitivity to social opportunity, and uncover a maturing role for BLA and its GluN2B receptors in social engagement.

Psychological Resilience in Adolescence as a function of Genetic Risk for Major Depressive Disorder and Alzheimer’s Disease

“…Extending these findings, it would be worth establishing whether the observed E/I link to resilience in MDD-vs AD-predisposed individuals manifests through distinguishable pathways (e.g., threat/loss-vs reward-linked). Such a line Polygenic Risk, Neurodevelopment and Resilience 17 of inquiry would be well-served by studies targeting neurotransmitter-specific substrates of whole-brain functional network interactions, while accounting for age-related modulation (73), including effective connectivity patterns between subcortical and cortical regions. This work would further benefit from experimental manipulations targeting the variety of mental processes (e.g., positive emotion upregulation vs negative emotion downregulation, 74) and cells-to-networks neurobiological mechanisms underlying resilience as a function of stressor and genetic vulnerability.…”

Developmental differences in amygdala projection neuron activation associated with isolation-driven changes in social preference

“…Our prior work shows that isolation increases activity in lateral and basal regions of the amygdala, and others have demonstrated critical roles for the NAc and septum in social behavior (Everts and Koolhaas, 1999;Manduca et al, 2016;Ferrara et al, 2021b). We were next interested in whether isolation differentially engages the activity of amygdala-NAc and -septal circuits sensitive to social circumstances to understand the impact of isolation on partner preference.…”

“…Many behaviors change over the course of development ( Campbell and Spear, 1972 ; Spear, 2000 ; Douglas et al, 2004 ; Pattwell et al, 2012 ; Loh et al, 2022 ). Adolescence is characterized by transitions in social engagement, where social play is gradually replaced by increases in social investigation [e.g., nose–body and anogenital sniffing; Hol et al (1999) ; Varlinskaya and Spear (2008) , and Ferrara et al (2021b) ]. Disruptions to the social repertoire especially during social maturation can have detrimental effects on socialization ( Hol et al, 1999 ; Schneider et al, 2016 ).…”

“…Manipulations of the social environment through deprivation or isolation can have a bidirectional impact on behavior. Long-term social disruption can impair social learning and interaction, and shorter-term isolation can facilitate age-specific social behaviors during adolescence ( Ferrara et al, 2021b ; Kinley et al, 2021 ; Lee et al, 2021 ; Caruso et al, 2022 ). This facilitation of social behavior with brief isolation can improve social recognition memory in adolescents, while reducing it in adults, which is indexed with increased novel partner investigation relative to a familiar ( Ferrara et al, 2022 ).…”

“…The amygdala is sensitive to and regulates social behavior ( Twining et al, 2017 ; Hu et al, 2021 ; Opendak et al, 2021 ; Terranova et al, 2022 ). Brief isolation can increase neuronal and microglial activity within both lateral (LA) and basal (BA) regions of the amygdala ( Ferrara et al, 2021b , 2022 ). The medial and basomedial amygdala subregions (MeA and BMA, respectively) are sensitive to the social environment and are critical for social memory, and may, therefore, be similarly sensitive to brief isolation ( Mesquita et al, 2016 ; Twining et al, 2017 ).…”