CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning

Abstract

SummaryNeurons within the dorsal and ventral striatum are often parsed into the two classes of spiny projection neurons, D1-containing and D2-containing neurons, and several classes of interneuron based on structure and function. However, with advanced technology and the appreciation of the importance of peptidergic neuromodulation, striatal neurons can be further and even differentially classified based on peptidergic content and function. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) in the nucleus accumbens (NAc) has been known for several decades. However, for the first time, we provide a comprehensive analysis of their identity and functional role in shaping reward learning, a critical function of the NAc. Here we show that the vast majority of NAc CRF neurons are spiny projection neurons (SPNs) comprised of D1-, D2- or D1/D2-containing SPNs. This unique population of NAc CRF neurons project to ventral pallidum and ventral midbrain and display both canonical and non-canonical SPN firing properties. We demonstrate that NAc CRF neurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning.