CCK- AND CCK+ BASAL AMYGDALA-NUCLEUS ACCUMBENS GLUTAMATE PRINCIPAL NEURONS: COMPARISON OF THEIR CIRCUITS AND INVOLVEMENT IN REWARD AND AVERSION PROCESSING

Basal nucleus of amygdala (BA) comprises primarily glutamatergic principal neurons, major efferents of which include nucleus accumbens (NAc) core and shell medium spiny neurons (MSNs) expressing dopamine receptor 1 (D1R) or 2. In male Fos-TRAP2 x Ai14 reporter mice, BA-NAc principal neurons were engaged in equal numbers and in a monovalent manner by reward or aversion. Cholecystokinin (CCK) has been proposed as a differential neuropeptide marker of reward (CCK-) and aversion (CCK+) glutamate neurons. Retrograde AAV vector labelling and CCK immunostaining demonstrated that 75% of BA-NAc neurons were CCK-. In CCK-Cre mice, using Cre-OFF/Cre-ON AAVs, BA CCK- and CCK+ neurons had distinct NAc projection pathways: CCK- neurons projected primarily to NAc medial core/shell and CCK+ neurons primarily to NAc core and lateral shell. Using Cre-OFF/Cre-ON eGRASP AAVs, in NAc core, BA CCK- neurons formed twice as many synapses with D1R-MSNs compared with CCK+ neurons. Building on these findings, the following experiments are on-going: (1) In Ai14 mice, retro-Fos-ERT2-Cre AAV expression in NAc, reward or aversion exposure, and neuronal TRAPing. BA-NAc tdTomato+ somata were collected for RNA-sequencing, including comparison of Cck expression in reward and aversion neurons. (2) In CCK-Cre mice, effects of DREADDs excitation of CCK- or CCK+ BA-NAc neurons on conditioned place preference/aversion. (3) In CCK-Cre mice, fiber photometry imaging of Ca²⁺ activity of CCK- or CCK+ BA-NAc neurons and glutamate and dopamine release at NAc D1R-MSNs during operant reward motivation and consummation. Overall findings will advance understanding of the BA-NAc signaling underlying adaptive reward motivation and aversion processing.