Serotonergic regulation of neuronal excitability and glutamatergic synaptic transmission in rat claustrum
- 1Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States
- 2University at Buffalo Neuroscience Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States
- 3Department of Neurobiology and Behavior, Cornell University, Ithaca, NY, United States
Abstract
The claustrum (CLA) receives dense serotonergic innervation from dorsal raphe nucleus (DRN) serotonin (5-HT) neurons, which are implicated in regulating sleep and stress homeostasis. However, the mechanisms by which 5-HT regulates the excitability of CLA neurons remain poorly defined. In the present study, we combined whole-cell patch-clamp recordings, 5-HT uncaging, and receptor pharmacology to examine the effects of 5-HT on the excitability of CLA neurons and their glutamatergic synapses. We found that 5-HT consistently induced membrane hyperpolarization or depolarization in regular-spiking type I and type II neurons, whereas it predominantly induced hyperpolarization in strongly adapting CLA neurons. The 5-HT-induced membrane hyperpolarization and depolarization were mediated by 5-HT1A receptors (5-HT1ARs) and 5-HT2A receptors (5-HT2ARs), respectively. Furthermore, we showed that activation of presynaptic 5-HT2ARs inhibits glutamatergic synaptic transmission in the CLA by reducing glutamate release. This effect was not mediated by the canonical phospholipase C (PLC) signaling cascade. Collectively, these findings reveal cell type-specific and multifaceted serotonergic modulation of the intrinsic excitability and synaptic transmission in the claustrum.
Related
- 5-HT1A and 5-HT2B receptor interaction and co-clustering regulate serotonergic neuron excitability
- Sequential maturation of supramammillary glutamatergic/GABAergic co-transmission onto adult-born dentate granule cells
- Synaptic microRNA dysregulation orchestrates aberrant glutamatergic transmission in a human neuronal model of 22q11.2 deletion syndrome
- Claustrum Morphometry Reveals Spatially Heterogeneous Alterations in 22q11DS
- The claustrum encodes and scales appetitive feeding
BibTeX
@article{rouleau2026serotonergic,
title = {{Serotonergic regulation of neuronal excitability and glutamatergic synaptic transmission in rat claustrum}},
author = {Renee Rouleau and Saida Oubraim and Lizemarie Cirone and Roh-Yu Shen and Samir Haj-Dahmane},
journal = {Frontiers in Cellular Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fncel.2026.1951375},
url = {https://doi.org/10.3389/fncel.2026.1951375},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Serotonergic regulation of neuronal excitability and glutamatergic synaptic transmission in rat claustrum
AU - Renee Rouleau
AU - Saida Oubraim
AU - Lizemarie Cirone
AU - Roh-Yu Shen
AU - Samir Haj-Dahmane
PY - 2026
DA - 2026/10/13
JO - Frontiers in Cellular Neuroscience
DO - 10.3389/fncel.2026.1951375
UR - https://doi.org/10.3389/fncel.2026.1951375
AB - The claustrum (CLA) receives dense serotonergic innervation from dorsal raphe nucleus (DRN) serotonin (5-HT) neurons, which are implicated in regulating sleep and stress homeostasis. However, the mechanisms by which 5-HT regulates the excitability of CLA neurons remain poorly defined. In the present study, we combined whole-cell patch-clamp recordings, 5-HT uncaging, and receptor pharmacology to examine the effects of 5-HT on the excitability of CLA neurons and their glutamatergic synapses. We found that 5-HT consistently induced membrane hyperpolarization or depolarization in regular-spiking type I and type II neurons, whereas it predominantly induced hyperpolarization in strongly adapting CLA neurons. The 5-HT-induced membrane hyperpolarization and depolarization were mediated by 5-HT1A receptors (5-HT1ARs) and 5-HT2A receptors (5-HT2ARs), respectively. Furthermore, we showed that activation of presynaptic 5-HT2ARs inhibits glutamatergic synaptic transmission in the CLA by reducing glutamate release. This effect was not mediated by the canonical phospholipase C (PLC) signaling cascade. Collectively, these findings reveal cell type-specific and multifaceted serotonergic modulation of the intrinsic excitability and synaptic transmission in the claustrum.
SN - 1662-5102
ER -