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Medial Prefrontal Cortex Serotonin Input Regulates Cognitive Flexibility in Mice.

Ashlea A Morgan, Nuno D Alves, Gregory S Stevens

    Biorxiv : the Preprint Server for Biology
    |April 10, 2023
    PubMed
    Summary

    Serotonin release in the medial prefrontal cortex (mPFC) directly inhibits neurons, but is essential for cognitive flexibility. This pathway from the dorsal raphe to the mPFC is key for adapting to changing rules.

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    Area of Science:

    • Neuroscience
    • Behavioral Neuroscience
    • Neuropharmacology

    Background:

    • The medial prefrontal cortex (mPFC) is crucial for cognitive flexibility and emotional regulation.
    • Serotonergic projections to the mPFC are known to influence cognition and emotion, but the specific role of endogenous serotonin release is unclear.

    Approach:

    • Investigated the direct effects of axonal serotonin release in the mPFC on neuronal activity and behavior.
    • Utilized *in vivo* optogenetics to activate or inhibit dorsal raphe to mPFC serotonergic pathways during a cognitive flexibility task.

    Key Points:

    • Axonal serotonin release in the mPFC directly inhibits major mPFC output neurons.
    • Endogenous serotonin release in the mPFC shows activity patterns related to reward anticipation and retrieval.
    • Optogenetic activation of this pathway enhanced cognitive flexibility, while inhibition impaired it, demonstrating necessity and sufficiency.

    Conclusions:

    • Endogenous serotonin release from dorsal raphe to mPFC neurons plays a critical and specific role in cognitive flexibility.
    • This modulatory role is specific to cognitive flexibility, as locomotor and anxiety-like behaviors were unaffected.