The serotonergic psychedelic N,N-dipropyltryptamine alters information-processing dynamics in in vitro cortical neural circuits

Most of the recent work in psychedelic neuroscience has been done using non-invasive neuroimaging, with data recorded from the brains of adult volunteers under the influence of a variety of drugs. While this data provides holistic insights into the effects of psychedelics on whole-brain dynamics, the effects of psychedelics on the meso-scale dynamics of neuronal circuits remains 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 post-natal rats. Three hours of spontaneous activity were recorded: an hour of pre-drug control, and 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 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 meso-scale neuronal networks in cortical tissue. Implications for existing hypotheses of psychedelic action, such as the Entropic Brain Hypothesis, are discussed.

In the last two decades, there has been an explosion of interest in the neural substrates of the psychedelic experience. Almost all of this work has focused on human neuroimaging with modalities like fMRI, EEG, MEG, etc. These approaches provide a coarse, whole-brain perspective on psychedelic drug action, but miss the fine-scale changes in neuron-level firing. This study uses in vitro recordings of organotypic cultures to explore how the serotonergic psychedelic N,N-DPT alters information-processing dynamics in networks of a few hundreds neurons. We find robust alterations to information dynamics, including changes to the global connectivity patterns suggestive of a changing integration/segregation balance. These results should inform future work on the neuro-biological basis of psychedelic drug actions.