| 1. |
- Brys, Ivani, et al.
(author)
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5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system
- 2023
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 6:1
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Journal article (peer-reviewed)abstract
- The profound changes in perception and cognition induced by psychedelic drugs are thought to act on several levels, including increased glutamatergic activity, altered functional connectivity and an aberrant increase in high-frequency oscillations. To bridge these different levels of observation, we have here performed large-scale multi-structure recordings in freely behaving rats treated with 5-HT2AR psychedelics (LSD, DOI) and NMDAR psychedelics (ketamine, PCP). While interneurons and principal cells showed disparate firing rate modulations for the two classes of psychedelics, the local field potentials revealed a shared pattern of synchronized high-frequency oscillations in the ventral striatum and several cortical areas. Remarkably, the phase differences between structures were close to zero, corresponding to <1 ms delays. Likely, this hypersynchrony has major effects on the integration of information across neuronal systems and we propose that it is a key contributor to changes in perception and cognition during psychedelic drug use. Potentially, similar mechanisms could induce hallucinations and delusions in psychotic disorders and would constitute promising targets for new antipsychotic treatments.
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| 2. |
- Nasretdinov, Azat, et al.
(author)
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Systems-level analysis of local field potentials reveals differential effects of lysergic acid diethylamide and ketamine on neuronal activity and functional connectivity
- 2023
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In: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 17
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Journal article (peer-reviewed)abstract
- Psychedelic substances have in recent years attracted considerable interest as potential treatments for several psychiatric conditions, including depression, anxiety, and addiction. Imaging studies in humans point to a number of possible mechanisms underlying the acute effects of psychedelics, including changes in neuronal firing rates and excitability as well as alterations in functional connectivity between various brain nodes. In addition, animal studies using invasive recordings, have suggested synchronous high-frequency oscillations involving several brain regions as another key feature of the psychedelic brain state. To better understand how the imaging data might be related to high-resolution electrophysiological measurements, we have here analyzed the aperiodic part of the local field potential (LFP) in rodents treated with a classic psychedelic (LSD) or a dissociative anesthetic (ketamine). In addition, functional connectivity, as quantified by mutual information measures in the LFP time series, has been assessed with in and between different structures. Our data suggest that the altered brain states of LSD and ketamine are caused by different underlying mechanisms, where LFP power shifts indicate increased neuronal activity but reduced connectivity following ketamine, while LSD also leads to reduced connectivity but without an accompanying change in LFP broadband power.
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