Medial prefrontal cortex to medial septum pathway activation improves cognitive flexibility in rats

Autor: David M Bortz, Catalina M Feistritzer, Anthony A Grace
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Neuropsychopharmacology.
ISSN: 1469-5111
1461-1457
DOI: 10.1093/ijnp/pyad019
Popis: Background The medial prefrontal cortex (mPFC) is necessary for cognitive flexibility and projects to medial septum (MS). MS activation improves strategy switching, a common measure of cognitive flexibility, via its ability to regulate midbrain dopamine (DA) neuron population activity. We hypothesized that the mPFC to MS pathway may be the mechanism by which the MS regulates strategy switching and DA neuron population activity. Methods Male and female rats learned a complex discrimination strategy across two different training time points: a constant length (10 days) and a variable length that coincided with each rat meeting an acquisition-level performance threshold (males-5.3 + 0.3 days, females-3.8 + 0.3 days). We then chemogenetically activated or inhibited the mPFC-MS pathway and measured each rat’s ability to inhibit the prior learned discrimination strategy and switch to a prior ignored discrimination strategy (strategy switching). Results Activation of the mPFC-MS pathway improved strategy switching after 10 days of training in both sexes, while inhibition of the pathway had little to no effect on strategy switching. Neither activation nor inhibition of the mPFC-MS pathway affected strategy switching following the acquisition-level performance threshold. Activation, but not inhibiton, of the mPFC-MS pathway bidirectionally regulated DA activity in ventral tegmental area and substantia nigra pars compacta, similar to MS activation. Conclusions This study presents a top-down circuit from the prefrontal cortex to the midbrain, with the MS being a critical contributor, by which DA activity can be manipulated to promote flexible behavior.
Databáze: OpenAIRE
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