The serotonergic psychedelic N,N-dipropyltryptamine alters information-processing dynamics in in vitro cortical neural circuits.
Thomas F. Varley, Daniel Havert, Leandro Fosque, Abolfazl Alipour, Naruepon Weerawongphrom, Hiroki Naganobori, Lily O’Shea, Maria Pope, John Beggs
Network Neuroscience December 10, 2024 DOI: 10.1162/netn_a_00408 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | In vitro organotypic cultures of cortical tissue from postnatal rats |
| Interventions | N N-diproptyltryptamine (DPT) |
| Dose | 10-μM DPT solution |
| Duration | Three hours of recording: one hour predrug control, one hour DPT exposure, one hour washout |
| Topics | Serotonin |
| Keywords | Psychedelics Brain research Neural communication Cognitive science |
| Citations | 12 |
| Key findings | DPT reversibly altered information dynamics in cortical tissue: it increased the entropy of spontaneous firing, reduced information storage time in individual neurons, reduced the reversibility of neural activity while increasing entropy production, decreased overall information flow into each neuron but increased weak connections, and decreased higher-order statistical synergy in sets of three neurons. The authors argue this pattern combines integration and disintegration and bears on hypotheses such as the entropic brain hypothesis. |
Abstract
Most of the recent work in psychedelic neuroscience has been done using noninvasive neuroimaging, with data recorded from the brains of adult volunteers under the influence of a variety of drugs. While these data provide holistic insights into the effects of psychedelics on whole-brain dynamics, the effects of psychedelics on the mesoscale dynamics of neuronal circuits remain much less explored. Here, we report the effects of the serotonergic psychedelic N,N-diproptyltryptamine (DPT) on information-processing dynamics in a sample of in vitro organotypic cultures of cortical tissue from postnatal rats. Three hours of spontaneous activity were recorded: an hour of predrug control, an hour of exposure to 10-μM DPT solution, and a final hour of washout, once again under control conditions. We found that DPT reversibly alters information dynamics in multiple ways: First, the DPT condition was associated with a higher entropy of spontaneous firing activity and reduced the amount of time information was stored in individual neurons. Second, DPT also reduced the reversibility of neural activity, increasing the entropy produced and suggesting a drive away from equilibrium. Third, DPT altered the structure of neuronal circuits, decreasing the overall information flow coming into each neuron, but increasing the number of weak connections, creating a dynamic that combines elements of integration and disintegration. Finally, DPT decreased the higher order statistical synergy present in sets of three neurons. Collectively, these results paint a complex picture of how psychedelics regulate information processing in mesoscale neuronal networks in cortical tissue. Implications for existing hypotheses of psychedelic action, such as the entropic brain hypothesis, are discussed.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 3
- The Causal Role of Consciousness in Psychedelic Therapy for Treatment-Resistant Depression: Hypothesis and Proposal ACS Pharmacology & Translational Science July 16, 2025
- How to set up a psychedelic study: Unique considerations for research involving human participants. Neuroscience & Biobehavioral Reviews July 1, 2026
- Preliminary analysis of ayahuasca-induced anatomical alterations in the somatosensory cortex of juvenile non-human primates (Callithrix jacchus) subjected to chronic stress Translational Psychiatry February 19, 2026
Cites 26
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
and 21 more in the library