bioRxiv (Cold Spring Harbor Laboratory)
October 23, 2023
Tyler G. Ekins, Isla Brooks, Sameer Kailasa et al.
17 citations
preprint
Classic psychedelic drugs, such as LSD and psilocybin, are thought to boost brain cell activity in the prefrontal cortex by activating serotonin 2A receptors. However, this research shows that these drugs actually suppress the intrinsic excitability of pyramidal neurons in a dose-dependent manner. The suppression is stronger when drugs are applied outside cells than inside, and it occurs through a previously unknown mechanism: enhancement of potassium M-current channels, independent of serotonin 2A receptor activation. Computer models reveal that M-current activation interacts with other mechanisms to reduce excitability and shorten working memory span. This suggests psychedelics may trigger widespread homeostatic adjustments that contribute to therapeutic benefits.
Molecular Psychiatry
March 1, 2026
Tyler G. Ekins, Chloe Rybicki-Kler, Tao Deng et al.
9 citations
Classic psychedelics can strengthen connections in the retrosplenial cortex, a brain region important for memory and spatial orientation that is impaired in Alzheimer's disease, even though its neurons lack the serotonin 2A receptors thought necessary for such effects. Using a new genetic tool in mice, the research shows that this strengthening depends on presynaptic serotonin 2A receptors on incoming nerve fibers from the anterior thalamus, not on the postsynaptic receptors of the retrosplenial cortex itself. The finding suggests psychedelics may have broader therapeutic potential than currently recognized, possibly aiding conditions like Alzheimer's disease and post-traumatic stress disorder by boosting retrosplenial circuit function.
Anesthesia and analgesia
June 1, 2022
Michael A Brito, Duan Li, Christopher W Fields et al.
Cortical acetylcholine levels correlate with neurophysiologic complexity and frontoparietal connectivity during altered states of consciousness. In rats under isoflurane anesthesia, subanesthetic ketamine (10 mg/kg/h) produced sustained increases in brain complexity and high gamma connectivity, accompanied by progressive rises in prefrontal (104%) and parietal (159%) acetylcholine. Nitrous oxide caused a transient increase in complexity and connectivity with smaller acetylcholine increases (prefrontal 56%, parietal 43%), followed by a later phase of decreased acetylcholine, reduced complexity, and weaker connectivity. These findings link cortical acetylcholine to changes in consciousness level.