Seronergic neuromodulation
Sensory perception originates from the integration of external stimuli with internal representations of the world, including prior expectations and behavioral states. In normal conditions, balancing new sensory evidence with internal models leads to flexible and accurate perception. Disrupted balance can lead to altered perception. The serotonin-2A receptor is associated with such perceptual alterations, both in its role in schizophrenia and in the action of psychedelic drugs. Experimental evidence presents an apparently contradictory picture of the effect of serotonergic modulation on neural circuits, increasing neuronal excitability while simultaneously reducing neural responses evoked by visual stimuli in behaving mice. Here, we leverage a synergistic collaboration with Cris Niell's lab to establish a new theory of serotonergic modulation and thereby reconcile these puzzling observations. Our mechanistic theory is based on a biologically plausible model of cortical processing, informed by the observed neuromodulation effects. We aim at explaining the mechanism mediating the effect of serotonergic modulation on visual processing. Motivated by recent human fMRI studies showing altered functional connectivity in the psychedelic state and schizophrenia, we investigate how serotonergic activation regulates the whole-brain functional connectivity and activity.
This project is aimed at elucidating the action of serotonergic psychedelics at the level of neural circuits and large-scale brain networks. Knowledge of these neural mechanisms may help prevent the recreational misuse of such drugs, as well as guide their safe use as potential therapeutics for neuropsychiatric disorders.
This project is aimed at elucidating the action of serotonergic psychedelics at the level of neural circuits and large-scale brain networks. Knowledge of these neural mechanisms may help prevent the recreational misuse of such drugs, as well as guide their safe use as potential therapeutics for neuropsychiatric disorders.