Serotonergic modulation of the claustrum

Abstract

The claustrum, whose function is hotly debated, is a small but densely connected brain structure. How exactly the claustrum is modulated by neuromodulators, including serotonin (5-HT), is understudied. Here, 5-HT responses in individual claustral neurons were investigated using whole-cell patch clamp, pharmacology, and caged compounds in ex vivo mouse brain slices. Claustral projection neurons (PNs) frequently produced a long-lasting inhibitory outward current that is mediated by K+ ions and mainly 5-HT receptor (5-HTR) -1A. The 5-HT current hyperpolarizes PNs because it reduced the firing properties of these PNs via a linear input subtraction. 5-HTRs causing the hyperpolarization were located at the soma and dendrites of PNs. Contrasting the PNs, the three claustral interneurons studied were either excited or inhibited by 5-HT but were not highly responsive to 5-HT. Taken together, 5-HT creates a net inhibition in the claustrum and decreases the claustrum’s sensitivity to input.