Striatal Cholinergic Interneurons Are a Novel Target of Corticotropin Releasing Factor

Julia Lemos, Jung Hoon Shin, Veronica A. Alvarez

Research output: Contribution to journalArticle

Abstract

Cholinergic interneurons (CINs) are critical regulators of striatal network activity and output. Changes in CIN activity are thought to encode salient changes in the environment and stimulus-response-outcome associations. Here we report that the stress-associated neuropeptide corticotropin releasing factor (CRF) produces a profound and reliable increase in the spontaneous firing of CINs in both dorsal striatum and nucleus accumbens (NAc) through activation of CRF type 1 receptors, production of cAMP and reduction in spike accommodation in male mice. The increase of CIN firing by CRF results in the activation muscarinic acetylcholine receptors type 5, which mediate potentiation of dopamine transmission in the striatum. This study provides critical mechanistic insight into how CRF modulates striatal activity and dopamine transmission in the NAc to likely account for CRF facilitation of appetitive behaviors.SIGNIFICANCE STATEMENT Although the presence of CRF receptors in the dorsal and ventral striatum has been acknowledged, the cellular identity and the functional consequences of receptor activation is unknown. Here we report that striatal cholinergic interneurons express CRF-R1 receptors and are acutely activated by the neuropeptide CRF that is released in response to salient environmental stimuli. Cholinergic interneurons make <1% of the cells in the striatum but are critical regulators of the striatal circuitry and its output. CRF's fast and potent activation of cholinergic interneurons could have far reaching behavioral implications across motivated behaviors controlled by the striatum.

Original languageEnglish (US)
Pages (from-to)5647-5661
Number of pages15
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume39
Issue number29
DOIs
StatePublished - Jul 17 2019

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Corpus Striatum
Corticotropin-Releasing Hormone
Interneurons
Cholinergic Agents
Corticotropin-Releasing Hormone Receptors
Nucleus Accumbens
Neuropeptides
Dopamine
Appetitive Behavior
Muscarinic Receptors

Keywords

  • acetylcholine
  • dopamine transmission
  • muscarinic receptors
  • nucleus accumbens
  • striatum

PubMed: MeSH publication types

  • Journal Article

Cite this

Striatal Cholinergic Interneurons Are a Novel Target of Corticotropin Releasing Factor. / Lemos, Julia; Shin, Jung Hoon; Alvarez, Veronica A.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 39, No. 29, 17.07.2019, p. 5647-5661.

Research output: Contribution to journalArticle

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