Medial Prefrontal Cortex Serotonin Input Regulates Cognitive Flexibility in Mice.

Autor: Morgan AA, Alves ND, Stevens GS, Yeasmin TT, Mackay A, Power S, Sargin D, Hanna C, Adib AL, Ziolkowski-Blake A, Lambe EK, Ansorge MS
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 30. Date of Electronic Publication: 2023 Mar 30.
DOI: 10.1101/2023.03.30.534775
Abstrakt: The medial prefrontal cortex (mPFC) regulates cognitive flexibility and emotional behavior. Neurons that release serotonin project to the mPFC, and serotonergic drugs influence emotion and cognition. Yet, the specific roles of endogenous serotonin release in the mPFC on neurophysiology and behavior are unknown. We show that axonal serotonin release in the mPFC directly inhibits the major mPFC output neurons. In serotonergic neurons projecting from the dorsal raphe to the mPFC, we find endogenous activity signatures pre-reward retrieval and at reward retrieval during a cognitive flexibility task. In vivo optogenetic activation of this pathway during pre-reward retrieval selectively improved extradimensional rule shift performance while inhibition impaired it, demonstrating sufficiency and necessity for mPFC serotonin release in cognitive flexibility. Locomotor activity and anxiety-like behavior were not affected by either optogenetic manipulation. Collectively, our data reveal a powerful and specific modulatory role of endogenous serotonin release from dorsal raphe-to-mPFC projecting neurons in cognitive flexibility.
Databáze: MEDLINE