Cholinergic interneurons in the nucleus accumbens are a site of cellular convergence for corticotropin release factor and estrogen regulation

Abstract

AbstractCholinergic interneurons (ChIs) act as master regulators of striatal output, finely tuning neurotransmission to control motivated behaviors. ChIs are a cellular target of many peptide and hormonal neuromodulators, including corticotropin releasing factor, opioids, insulin and leptin, which can influence an animal’s behavior by signaling stress, pleasure, pain and nutritional status. However, little is known about how sex hormones via estrogen receptors influence the function of these other neuromodulators. Here, we performed in situ hybridization on mouse striatal tissue to characterize the effect of sex and sex hormones on choline acetyltransferase (Chat), estrogen receptor alpha (Esr1), and corticotropin releasing factor type 1 receptor (Crhr1) expression. Although we did not detect sex differences in ChAT protein levels in the striatum, we found that female mice have moreChatmRNA-expressing neurons than males. At the population level, we observed a sexually dimorphic distribution ofEsr1- andCrhr1-expressing ChIs in the ventral striatum that demonstrates an antagonistic correlational relationship, which is abolished by ovariectomy. Only in the NAc did we find a significant population of ChIs that co-expressCrhr1andEsr1. At the cellular level,Crhr1andEsr1transcript levels were negatively correlated only during estrus, indicating that changes in sex hormones levels can modulate the interaction betweenCrhr1andEsr1mRNA levels. Together, these data provide evidence for the unique expression and interaction ofEsr1andCrhr1in ventral striatal ChIs, warranting further investigation into how these transcriptomic patterns might underlie important functions for ChIs at the intersection of stress and reproductive behaviors.