5-HT1A and 5-HT2B receptor interaction and co-clustering regulate serotonergic neuron excitability
Abstract
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 1A 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 1A and 5-HT 2B receptors can form heterodimers and co-cluster at the plasma membrane of dendrites. Selective agonist stimulation of coexpressed 5-HT 1A and 5-HT 2B receptors prevents 5-HT 1A receptor internalization and increases 5-HT 2B receptor membrane clustering. Current clamp recordings of 5-HT neurons revealed that 5-HT 1A receptor stimulation of acute slices from mice lacking 5-HT 2B receptors in 5-HT neurons increased their firing activity trough Ca 2+ -activated potassium channel inhibition compared to 5-HT neurons from control mice. This work supports the hypothesis that the relative expression of 5-HT 1A and 5-HT 2B receptors tunes the neuronal excitability of serotonergic neurons through potassium channel regulation.
Related
- Serotonergic regulation of neuronal excitability and glutamatergic synaptic transmission in rat claustrum
- The interaction between NC(p7)1-55 and p6 may regulate interactions with nucleic acids during assembly through modulation of Gag folding.
- Neuropeptide NLP-40 and Cognate G- Protein Coupled Receptor AEX-2 Regulate Behavioral Responses During Anoxia in Caenorhabditis elegans
- Cell-Hub Database: a consolidated multi-species ligand-receptor interaction resource for cell-cell communication analysis
- Serotonergic modulation of sacral dorsal root stimulation-induced locomotor output in newborn rat
BibTeX
@article{benhadda20265ht1a,
title = {{5-HT1A and 5-HT2B receptor interaction and co-clustering regulate serotonergic neuron excitability}},
author = {Amina Benhadda and Célia Delhaye and Imane Moutkine and Xavier Marques and Marion Russeau and Corentin Le Magueresse and Anne Roumier and Sabine Lévi and Luc Maroteaux},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2023.107401},
url = {https://hal.science/hal-05783999v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - 5-HT1A and 5-HT2B receptor interaction and co-clustering regulate serotonergic neuron excitability
AU - Amina Benhadda
AU - Célia Delhaye
AU - Imane Moutkine
AU - Xavier Marques
AU - Marion Russeau
AU - Corentin Le Magueresse
AU - Anne Roumier
AU - Sabine Lévi
AU - Luc Maroteaux
PY - 2026
DA - 2026/10/07
JO - iScience
DO - 10.1016/j.isci.2023.107401
UR - https://hal.science/hal-05783999v1
AB - 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 1A 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 1A and 5-HT 2B receptors can form heterodimers and co-cluster at the plasma membrane of dendrites. Selective agonist stimulation of coexpressed 5-HT 1A and 5-HT 2B receptors prevents 5-HT 1A receptor internalization and increases 5-HT 2B receptor membrane clustering. Current clamp recordings of 5-HT neurons revealed that 5-HT 1A receptor stimulation of acute slices from mice lacking 5-HT 2B receptors in 5-HT neurons increased their firing activity trough Ca 2+ -activated potassium channel inhibition compared to 5-HT neurons from control mice. This work supports the hypothesis that the relative expression of 5-HT 1A and 5-HT 2B receptors tunes the neuronal excitability of serotonergic neurons through potassium channel regulation.
SN - 2589-0042
ER -