CCK+ Interneurons Contribute to Thalamus-Evoked Feed-Forward Inhibition in the Prelimbic Prefrontal Cortex

• DOI: 10.1523/jneurosci.0957-23.2024
• Publication Date: 2024-05-02T17:50:22Z
• Authors: Aichurok Kamalova; Kasra Manoocheri; Xingchen Liu; Sanne M. Casello; Matthew Huang; Corey Baimel; Emily V. Jang; Paul G. Anastasiades; David P. Collins; Adam G. Carter
• Keywords: Infralimbic cortex; Interneuron

Interneurons in the medial prefrontal cortex (PFC) regulate local neural activity to influence cognitive, motivated, and emotional behaviors. Parvalbumin-expressing (PV+) interneurons are primary mediators of thalamus-evoked feed-forward inhibition across mouse cortex, including anterior cingulate where they engaged by inputs from mediodorsal (MD) thalamus. In contrast, adjacent prelimbic (PL) we find that PV+ scarce principal thalamorecipient layer 3 (L3), suggesting distinct mechanisms inhibition. To identify mediate MD-evoked PL, combine slice physiology, optogenetics, intersectional genetic tools mice both sexes. We expressing cholecystokinin (CCK+) abundant L3 with cells exhibiting fast-spiking (fs) or nonfast-spiking (nfs) properties. MD make stronger connections onto fs-CCK+ interneurons, driving them fire more readily than nearby pyramidal other interneurons. CCK+ turn inhibitory, perisomatic cells, exhibit cannabinoid 1 receptor (CB1R) mediated modulation. Moreover, inhibition, but not direct excitation, is also sensitive CB1R Our findings indicate contribute revealing a mechanism which cannabinoids can modulate MD-PFC communication.