Cellular rules underlying psychedelic control of prefrontal pyramidal neurons.

ABSTRACT: Classical psychedelic drugs are thought to increase excitability of pyramidal cells in prefrontal cortex via activation of serotonin 2_A receptors (5-HT2_ARs). Here, we instead find that multiple classes of psychedelics dose-dependently suppress intrinsic excitability of pyramidal neurons, and that extracellular delivery of psychedelics decreases excitability significantly more than intracellular delivery. A previously unknown mechanism underlies this psychedelic drug action: enhancement of ubiquitously expressed potassium "M-current" channels that is independent of 5-HT2R activation. Using machine-learning-based data assimilation models, we show that M-current activation interacts with previously described mechanisms to dramatically reduce intrinsic excitability and sh

SUBMITTER: Ekins TG 

PROVIDER: S-EPMC10634703 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature