5-HT 1A and 5-HT 2B receptor interaction and co-clustering regulate serotonergic neuron excitability

Many psychiatric diseases have been associated with serotonin (5-HT) neuron dysfunction. The firing of 5-HT neurons is known to be under 5-HT receptor-mediated autoinhibition, but functional consequences of coexpressed receptors are unknown. Using co-immunoprecipitation, BRET, confocal, and super-re...

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Bibliographic Details
Published iniScience Vol. 26; no. 8; p. 107401
Main Authors Benhadda, Amina, Delhaye, Célia, Moutkine, Imane, Marques, Xavier, Russeau, Marion, Le Magueresse, Corentin, Roumier, Anne, Lévi, Sabine, Maroteaux, Luc
Format Journal Article
LanguageEnglish
Published United States 18.08.2023
Subjects
Neuroscience
Cell biology
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Summary:Many psychiatric diseases have been associated with serotonin (5-HT) neuron dysfunction. The firing of 5-HT neurons is known to be under 5-HT receptor-mediated autoinhibition, but functional consequences of coexpressed receptors are unknown. Using co-immunoprecipitation, BRET, confocal, and super-resolution microscopy in hippocampal and 5-HT neurons, we present evidence that 5-HT and 5-HT receptors can form heterodimers and co-cluster at the plasma membrane of dendrites. Selective agonist stimulation of coexpressed 5-HT and 5-HT receptors prevents 5-HT receptor internalization and increases 5-HT receptor membrane clustering. Current clamp recordings of 5-HT neurons revealed that 5-HT receptor stimulation of acute slices from mice lacking 5-HT receptors in 5-HT neurons increased their firing activity trough Ca -activated potassium channel inhibition compared to 5-HT neurons from control mice. This work supports the hypothesis that the relative expression of 5-HT and 5-HT receptors tunes the neuronal excitability of serotonergic neurons through potassium channel regulation.
ISSN:2589-0042