BEHAVIORAL AND NETWORK-LEVEL EFFECTS OF PSYCHEDELIC DRUGS IN LARVAL ZEBRAFISH

Psychedelic drugs produce profound changes in perception and cognition, yet the network-level mechanisms underlying these altered brain states remain unclear. In this study, we investigated the effects of psychedelic exposure on behavior in larval zebrafish and neuronal activity in the optic tectum, a key sensory-motor integration center.
Larval zebrafish were exposed to psychedelic compounds for 8 hrs prior to quantification of overall locomotor activity. Separately, calcium imaging fluctuations were captured to measure neuronal activity in the optic tectum. Neural data were analyzed using dimensionality reduction and population-level metrics to characterize low-dimensional structure, variability, and coordination of population activity. In parallel, we explored recurrent neural network models trained on experimentally recorded calcium activity as a data-driven approach.
Behavioral analyses revealed reproducible drug-dependent increases in total locomotor activity compared to control conditions, consistent with previous reports (Braun et al., Mol. Psychiatry 2024). Regarding calcium imaging, mean activity levels were largely similar across conditions in the current analyses; however, ongoing population-level analyses suggest potential changes in neural coordination, including altered correlation structure, indicating that drug effects may be expressed through reorganization of network dynamics. Preliminary modeling suggests that recurrent networks constrained by experimental data can reproduce aspects of these dynamics and provide a framework for comparing network regimes across conditions.
Together, this work establishes a behavioral effect of psychedelic drug exposure in zebrafish and outlines an ongoing effort to link these effects to neural population dynamics in a downstream sensory-motor region, highlighting the utility of population-level analyses and data-constrained modeling.