Engagement of basal amygdala-nucleus accumbens glutamate neurons in the processing of rewarding or aversive social stimuli.

Basal amygdala (BA) neurons projecting to nucleus accumbens (NAc) core/shell are primarily glutamatergic and are integral to the circuitry of emotional processing. Several recent mouse studies have addressed whether neurons in this population(s) respond to reward, aversion or both emotional valences. The focus has been on processing of physical emotional stimuli, and here, we extend this to salient social stimuli. In male mice, an iterative study was conducted into engagement of BA-NAc neurons in response to estrous female (social reward, SR) and/or aggressive-dominant male (social aversion, SA). In BL/6J mice, SR and SA activated c-Fos expression in a high and similar number/density of BA-NAc neurons in the anteroposterior intermediate BA (int-BA), whereas activation was predominantly by SA in posterior (post-)BA. In Fos-TRAP2 mice, compared with SR-SR or SA-SA controls, exposure to successive presentation of SR-SA or SA-SR, followed by assessment of tdTomato reporter and/or c-Fos expression, demonstrated that many int-BA-NAc neurons were activated by only one of SR and SA; these SR/SA monovalent neurons were similar in number and present in both magnocellular and parvocellular int-BA subregions. In freely moving BL/6J mice exposed to SR, bulk GCaMP6 fibre photometry provided confirmatory in vivo evidence for engagement of int-BA-NAc neurons during social and sexual interactions. Therefore, populations of BA-NAc glutamate neurons are engaged by salient rewarding and aversive social stimuli in a topographic and valence-specific manner; this novel evidence is important to the overall understanding of the roles of this pathway in the circuitry of socio-emotional processing.

Stress deficits in reward behaviour are associated with and replicated by dysregulated amygdala-nucleus accumbens pathway function in mice.

Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Glutamate neurons in basal amygdala (BA) project to various regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) leads to reduced discriminative reward learning (DRL) associated with decreased BA-NAc activity, and to reduced reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc activity. Chronic tetanus toxin BA-NAc inhibition replicates the CSS-DRL effect and causes a mild REV reduction, whilst chronic DREADDs BA-NAc activation replicates the CSS effect on REV without affecting DRL. This study provides evidence that stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate opposite activity changes in reward (learning) neurons and aversion (effort) neurons in the BA-NAc pathway following chronic stress.