Cortical Mechanisms Contributing to Ketamine-Induced Dissociation
The Neuroscientist December 26, 2025 Kallol Bera, Loren L. Looger, Alex Proekt et al. 5 citations
Ketamine, an anesthetic that produces dissociative anesthesia—characterized by perceptual detachment, analgesia, and altered consciousness—also acts as a rapid antidepressant at low doses and serves as a tool to study consciousness and neuropsychiatric disorders. Its effects stem from actions on cortical circuits: blocking NMDA receptors and HCN1 channels, disinhibiting pyramidal neurons, and altering thalamocortical connectivity. The review synthesizes findings from pharmacology, cell-specific imaging, and systems neuroscience to explain how ketamine alters cortical dynamics to drive dissociation. It also explores the possibility that ketamine enters intracellular compartments, modulating neuronal excitability, signaling, and epigenetic state after a single dose. Understanding these processes may inform new treatments for treatment-resistant depression and the study of consciousness.