Journal of Neuroscience
December 1, 2000
Jennifer L. Scruggs, Sachin Patel, Michael Bubser et al.
154 citations
A hallucinogenic drug that activates 5-HT2A receptors increases Fos protein expression in the rat somatosensory cortex. This effect depends on 5-HT2A, not 5-HT2C, receptors and requires intact thalamocortical connections. The drug does not act directly on cortical neurons but instead stimulates 5-HT2A receptors on thalamocortical neurons, increasing glutamate release, which then drives Fos expression in cortical neurons via AMPA receptors. Blocking AMPA/KA receptors or lesioning the ventrobasal thalamus reduces the effect. These findings illuminate how hallucinogens produce their effects through a thalamocortical glutamate pathway.
bioRxiv (Cold Spring Harbor Laboratory)
September 26, 2023
Yi-Ting Chiu, Wei Wang, Pierre Llorach et al.
15 citations
preprint
Psychedelic drugs such as LSD and psilocybin show promise as treatments for depression, anxiety, PTSD, migraine, and cluster headaches by activating the 5-HT2A receptor (HTR2A). Researchers engineered several new mouse lines to study the role of HTR2A and the neurons that express it. One line allows visualization of the receptor and identification of HTR2A-containing cells, providing a detailed anatomical map. Another line has a humanized version of the receptor, and a third enables targeted genetic manipulation. The mice exhibited expected behavioral responses to psychedelics, confirming their usefulness. Electrophysiology showed that serotonin increases firing of specific pyramidal neurons through HTR2A, consistent with the receptor's location on the cell surface. These tools will help clarify how psychedelics work at molecular, cellular, and behavioral levels.