Decoupling of cortical activity from behavioral state following administration of the classic psychedelic DOI.

Autor: Olson RJ; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland OR 97239, USA., Bartlett L; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland OR 97239, USA., Sonneborn A; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland OR 97239, USA., Milton R; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland OR 97239, USA., Bretton-Granatoor Z; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10034, USA., Firdous A; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10034, USA., Harris AZ; Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10034, USA; Department of Psychiatry, Columbia University, New York, NY, 10034, USA., Abbas AI; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland OR 97239, USA; Department of Psychiatry, Oregon Health and Science University, Portland OR 97239, USA; VA Portland Health Care System, Portland OR, 97239, USA. Electronic address: abbasat@ohsu.edu.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2024 Oct 01; Vol. 257, pp. 110030. Date of Electronic Publication: 2024 Jun 06.
DOI: 10.1016/j.neuropharm.2024.110030
Abstrakt: Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit basis for the alterations in experience caused by CPs requires further study. The medial prefrontal cortex (mPFC), where CPs have been shown to induce rapid, 5-HT 2A receptor-dependent structural and neurophysiological changes, is believed to be a key site of action. To investigate the acute neural circuit changes induced by CPs, we recorded single neurons and local field potentials in the mPFC of freely behaving male mice after administration of the 5-HT 2A/2C receptor-selective CP, 2,5-Dimethoxy-4-iodoamphetamine (DOI). We segregated recordings into active and rest periods in order to examine cortical activity during desynchronized (active) and synchronized (rest) states. We found that DOI induced a robust decrease in low frequency power when animals were at rest, attenuating the usual synchronization that occurs during less active behavioral states. DOI also increased broadband gamma power and suppressed activity in fast-spiking neurons in both active and rest periods. Together, these results suggest that the CP DOI induces persistent desynchronization in mPFC, including during rest when mPFC typically exhibits more synchronized activity. This shift in cortical dynamics may in part underlie the longer-lasting effects of CPs on plasticity, and may be critical to their therapeutic properties.
Competing Interests: Declaration of competing interest The authors have no competing interests to declare.
(Published by Elsevier Ltd.)
Databáze: MEDLINE
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