Corticotropin releasing factor alters the functional diversity of accumbal cholinergic interneurons

Abstract

AbstractCholinergic interneurons (ChIs) provide the main source of acetylcholine in the striatum and have emerged as a critical modulator of behavioral flexibility, motivation, and associative learning. In the dorsal striatum, ChIs display heterogeneous firing patterns. Here, we investigated the spontaneous firing patterns of ChIs in the nucleus accumbens (NAc) shell, a region of the ventral striatum. Using male and female mice, we performed cell-attached patch clamp electrophysiology recordings from ChIs. We identified four distinct ChI firing signatures: regular single-spiking, irregular single-spiking, rhythmic bursting followed by pauses or low activity, and a mixed-mode pattern composed of bursting activity and regular single spiking. ChIs from females had lower firing rates compared to males and had both a higher proportion of mixed-mode firing patterns and a lower proportion of regular single-spiking neurons compared to males. We further observed that across the estrous cycle, the estrus phase was characterized by higher proportions of mixed-mode, rhythmic bursting, and irregular ChI firing patterns compared to other phases. ChI firing mode was not driven by glutamatergic synaptic transmission in the slice preparation. Using pooled data from males and females, we examined the how the stress-associated neuropeptide corticotropin releasing factor (CRF) impacts these firing patterns. ChI firing patterns showed differential sensitivity to CRF. Furthermore, CRF shifted the proportion of ChI firing patterns toward more regular spiking activity over bursting patterns. These findings highlight the heterogeneous nature of ChI firing patterns, which may have implications for accumbal-dependent motivated behaviors.New and NoteworthyChIs within the dorsal and ventral striatum can exert a huge influence on network output and motivated behaviors. However, the firing patterns and neuromodulation of ChIs within the ventral striatum,specifically the NAc shell, are understudied. Here we report that NAc shell ChIs have a heterogenous distribution of ChI firing patterns that are labile and can be modulated by the stress-linked neuropeptide CRF and by estrous cycle.