# CRCNS: A mechanistic theory of serotonergic modulation of cortical processing

> **NIH NIH R01** · UNIVERSITY OF OREGON · 2024 · $353,881

## Abstract

PROJECT SUMMARY (See instructions):
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 will leverage a synergistic collaboration between theory and experiment to establish a new
theoretical framework for dissecting the neural mechanisms 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 will combine modeling and
experiment to explain the circuit 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 will elucidate how serotonergic activation regulates the
whole-brain functional connectivity from wide field calcium imaging recordings. Our model predictions will
be tested using optogenetic manipulations in a series of new electrophysiology and imaging experiments in
behaving mice.

## Key facts

- **NIH application ID:** 10870224
- **Project number:** 5R01DA055439-04
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Luca Mazzucato
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $353,881
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870224

## Citation

> US National Institutes of Health, RePORTER application 10870224, CRCNS: A mechanistic theory of serotonergic modulation of cortical processing (5R01DA055439-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10870224. Licensed CC0.

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