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Updated: Mar 18, 2026

Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
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, Israel.
None:
Striatal cholinergic interneurons (CINs) can drive local dopamine release via nicotinic acetylcholine receptors (nAChRs) expressed on dopaminergic axons, but their role in modulating serotonin (5-HT) signaling is poorly understood. Here, we show that synchronous activation of CINs directly triggers local 5-HT release in the dorsal striatum via nAChRs expressed on serotonergic axons. This CIN-5-HT coupling is not detectable in the ventral striatum, despite its substantially denser serotonergic innervation. The nAChR-dependent release not only increases 5-HT levels in the dorsal striatum, but also expands the spatial footprint of serotonergic signaling. In Sapap3-/- mice, a model of obsessive-compulsive disorder (OCD)-like behavior, this mechanism is exaggerated due to a hypercholinergic state, selectively amplifying the nAChR-dependent component of monoamine release. These findings demonstrate a regionally confined form of acetylcholine-5-HT crosstalk in the striatum and identify CINs as regulators of 5-HT dynamics in both healthy and pathological states.
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