The sodium leak channel drives a glutamatergic projection from dorsal dentate gyrus to medial septum for normal social interactions

Abstract

Chronic stress deficits social behaviors which involve malfunction of dentate gyrus (DG). However, the exact molecular mechanism and/or neural circuit of DG participated in social impairments induced by chronic stress is largely unknown. Here, we report that the sodium leak channel (NALCN) reduction in the dorsal DG (dDG) but not the ventral DG (vDG) induces social deficit of chronic stress through lowering the excitability and the firings of the glutamatergic neurons. Furthermore, we reveal the medial septum (MS) is an important downstream projection region of the dDG glutamatergic neurons involved in the social impairments of chronic stress and activating the dDG-MS glutamatergic projection significantly relieves these social deficits. In summary, these findings indicate that NALCN in the dDG glutamatergic neurons presents a promising molecular target for social deficit of chronic stress via influencing the activity of the dDG glutamatergic neurons (dDG^Glu) and their projection to the MS.