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Peer-reviewedCC BY 4.0Frontiers in Cellular Neuroscience

Serotonergic regulation of neuronal excitability and glutamatergic synaptic transmission in rat claustrum

  1. 1Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States
  2. 2University at Buffalo Neuroscience Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States
  3. 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.

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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  -