Serotonin Inhibition of Claustrum Projection Neurons: Ionic Mechanism, Receptor Subtypes and Consequences for Claustrum Computation

血清素对隔膜投射神经元的抑制:离子机制、受体亚型及其对隔膜计算的影响

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作者:Kelly Li Lin Wong, Martin Graf, George J Augustine

Abstract

The claustrum is a small but densely interconnected brain structure that is innervated by axons containing serotonin (5-HT), a neuromodulator that has been implicated in control of sleep and in the actions of psychedelic drugs. However, little is known about how 5-HT influences the claustrum. We have combined whole-cell patch-clamp measurements of ionic currents, flash photolysis, and receptor pharmacology to characterize the 5-HT responses of individual claustral projection neurons (PNs) in mouse brain slices. Serotonin application elicited a long-lasting outward current in claustral PNs. This current was due to an increase in membrane permeability to K+ ions and was mediated mainly by the type 1A 5-HT receptor (5-HTR-1A). The 5-HT-induced K+ current hyperpolarized, and thereby inhibited, the PNs by reducing action potential firing. Focal uncaging of 5-HT revealed that inhibitory 5-HTR-1As were located at both the soma and dendrites of PNs. We conclude that 5-HT creates a net inhibition in the claustrum, an action that should decrease claustrum sensitivity to excitatory input from other brain areas and thereby contribute to 5-HT action in the brain.

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