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

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 hav...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2024-11, Vol.13 (23), p.1980
Main Authors: Wong, Kelly Li Lin, Graf, Martin, Augustine, George J
Format: Article
Language:English
Subjects:
Acids
Action potential
Action Potentials - drug effects
Animals
Axons
Basal ganglia
Brain
Brain slice preparation
claustrum
Claustrum - metabolism
Drugs
Experiments
Flash photolysis
Hallucinogenic drugs
Male
Membrane permeability
Mice
Mice, Inbred C57BL
Neuromodulation
Neurons
Neurons - drug effects
Neurons - metabolism
Neurophysiology
Phenols
Photolysis
Psychedelic drugs
Receptor, Serotonin, 5-HT1A - metabolism
Receptors, Serotonin - metabolism
Serotonin
Serotonin - metabolism
Serotonin - pharmacology
Sleep
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells13231980