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Dietmar Schmitz

3 papers in the library · 14 citations · publishing 2007-2024

Papers

Synthetic surprise as the foundation of the psychedelic experience

Neuroscience & Biobehavioral Reviews January 15, 2024 Dietmar Schmitz, Roberto de Filippo 13 citations

Psychedelic agents like LSD and psilocybin alter consciousness by activating the 5-HT2A receptor. The authors hypothesize that these drugs enforce a state of synthetic surprise through biased activation of the 5-HT receptor system, drawing on recent insights into serotonin's role in signaling surprise. Within the predictive coding framework, surprise corresponds to prediction error—the mismatch between predictions and sensory input. The precision of prediction error determines its effect on priors, allowing dynamic interaction between top-down expectations and incoming data. Integrating findings on predictive coding circuitry and 5-HT2A receptor transcriptomic data, the authors propose a biological implementation emphasizing inhibitory interneurons. This has implications for clinical use, where psychedelics may disrupt maladaptive patterns by inducing surprise.

Somatostatin interneurons activated by 5-HT2A receptor suppress slow oscillations in medial entorhinal cortex

bioRxiv Preprint Server May 26, 2020 Roberto De Filippo, Benjamin R. Rost, Alexander Stumpf et al. 1 citation preprint

Serotonin (5-HT) is a key neuromodulator in the mammalian brain, but how it affects synchronized cortical network activity is not fully understood. This work shows that MDMA and fenfluramine, two drugs that release 5-HT, inhibit slow oscillations—a default cortical activity pattern—in the entorhinal cortex of anesthetized mice. The suppression occurs through activation of somatostatin-expressing interneurons via the 5-HT2A receptor. Because 5-HT2A receptor signaling is implicated in psychiatric disorders and mediates effects of serotonergic drugs, this link between these interneurons and serotonin may help clarify these complex topics.

Increased inhibitory input to CA1 pyramidal cells alters hippocampal gamma frequency oscillations in the MK-801 model of acute psychosis.

Neurobiology of disease March 1, 2007 Colin Kehrer, Tamar Dugladze, Nino Maziashvili et al.

Exposure to the compound MK-801, which induces psychosis-like symptoms similar to those in acute schizophrenia, alters brain activity in an animal model. Gamma frequency oscillations in the hippocampus, evoked by kainate, were more powerful in animals that had received MK-801 than in controls. The resting membrane potential of pyramidal cells was more depolarized after MK-801, while other membrane properties remained unchanged. The authors suggest that changes in sodium-potassium pump activity and increased phasic inhibition may underlie these effects.