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Synchronous activation of striatal cholinergic interneurons induces local serotonin release
Lior Matityahu1, Zachary B Hobel2, Noa Berkowitz1
1Department of Medical Neurobiology, Institute of Medical Research Israel - Canada, Faculty of the Medicine, The Hebrew University of Jerusalem, Jerusalem, 9112102, Israel.
Biorxiv : the Preprint Server for Biology
|November 18, 2024
Summary
Synchronous activation of striatal cholinergic interneurons (CINs) triggers serotonin release, similar to dopamine. This mechanism is amplified in a mouse model of OCD-like behavior, highlighting CINs
Area of Science:
- Neuroscience
- Neurobiology
- Striatal circuitry
Background:
- Striatal cholinergic interneurons (CINs) are known to modulate dopamine release by activating nicotinic acetylcholine receptors on dopamine axons.
- The precise mechanisms by which CINs influence other neurotransmitter systems, particularly serotonin, remain less understood.
Purpose of the Study:
- To investigate the role of synchronous CIN activation in regulating local serotonin release within the striatum.
- To determine if this CIN-mediated serotonin release mechanism is altered in pathological conditions associated with hypercholinergic states, such as obsessive-compulsive disorder (OCD)-like behavior.
Main Methods:
- Utilizing in vivo electrophysiological recordings in mouse striatum to monitor neurotransmitter release.
- Employing optogenetic or chemogenetic stimulation techniques to selectively activate CINs.
- Analyzing neurotransmitter dynamics in response to CIN activation in both wild-type and genetically modified mouse models.
Main Results:
- Synchronous activation of CINs was found to induce and extend the range of local serotonin release in the striatum.
- This CIN-driven serotonin release mechanism operates via a pathway involving nicotinic acetylcholine receptors, analogous to its effect on dopamine.
- The induction and extent of serotonin release by CINs were significantly exaggerated in the hypercholinergic striatum of a mouse model exhibiting OCD-like behavior.
Conclusions:
- CINs play a critical role in regulating local striatal serotonin release through a nicotinic acetylcholine receptor-dependent mechanism.
- Dysregulation of this CIN-serotonin pathway may contribute to the pathophysiology of conditions characterized by hypercholinergic activity and altered striatal function, such as OCD.
- These findings identify CINs as key regulators of both dopamine and serotonin signaling in the healthy and diseased striatum.
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