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Publication : Psilocybin decreases neural responsiveness and increases functional connectivity while preserving pure-tone frequency selectivity in mouse auditory cortex.

First Author  Brockett AT Year  2024
Journal  J Neurophysiol Volume  132
Issue  1 Pages  45-53
PubMed ID  38810366 Mgi Jnum  J:354914
Mgi Id  MGI:7736846 Doi  10.1152/jn.00124.2024
Citation  Brockett AT, et al. (2024) Psilocybin decreases neural responsiveness and increases functional connectivity while preserving pure-tone frequency selectivity in mouse auditory cortex. J Neurophysiol 132(1):45-53
abstractText  Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted two-photon imaging experiments in auditory cortex of awake mice and collected video of free-roaming mouse behavior, both at baseline and during psilocybin treatment. In comparison with pre-dose neural activity, a 2 mg/kg ip dose of psilocybin initially increased the amplitude of neural responses to sound. Thirty minutes post-dose, behavioral activity and neural response amplitudes decreased, yet functional connectivity increased. In contrast, control mice given intraperitoneal saline injections showed no significant changes in either neural or behavioral activity across conditions. Notably, neuronal stimulus selectivity remained stable during psilocybin treatment, for both tonotopic cortical maps and single-cell pure-tone frequency tuning curves. Our results mirror similar findings regarding the effects of serotonergic psychedelics in visual cortex and suggest that psilocybin modulates the balance of intrinsic versus stimulus-driven influences on neural activity in auditory cortex.NEW & NOTEWORTHY Recent studies have shown promising therapeutic potential for psychedelics in treating neuropsychiatric conditions. Musical experience during psilocybin-assisted therapy is predictive of treatment outcome, yet little is known about how psilocybin affects auditory processing. Here, we conducted two-photon imaging experiments in auditory cortex of awake mice that received a dose of psilocybin. Our results suggest that psilocybin modulates the roles of intrinsic neural activity versus stimulus-driven influences on auditory perception.
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