# Developmental origins of mental illness: evolution and reversibility

> **NIH NIH P50** · HARVARD UNIVERSITY · 2020 · $184,250

## Abstract

Abstract:
Altered network dynamics (brain rhythms) underlie most if not all brain disorders, yet we know
almost nothing about how such dynamics evolve in functional relationship to normal behavior.
Leveraging existing physiological data from the parent Conte grant to generate biophysically
detailed computational models, the proposed project constructs a circuit-based strategy for
tracking interneuron function and targeted intervention that involves network dynamics. We will
construct models of critical period dynamics to understand the essential mechanisms underlying
the transition from a predominantly inhibitory dynamic to the emergence of networks involving
pyramidal cells and interneurons, characteristic of cortical network processing in the adult brain.
Previous data suggests that the transformation is begun with a gamma oscillation provided by
networks of only inhibitory cells (ING). We hypothesize that ING is the initial stage in the
transformation of the immature cortical network, in which sensory input is ubiquitously
processed, to a more adult-like network state in which sophisticated, cortical processing of
sensory input occurs, including gating and working memory. We hypothesize the transformation
involves changes in network interactions between thalamus and cortex. We will perform data
analysis on existing data to investigate how this process normally evolves over time and how it
is derailed in the MeCP2 mouse model of Rett Syndrome and rescued by cell-specific gene
restoration. We anticipate this pioneering computational psychiatry approach to be broadly
applicable to many neurodevelopmental disorders beyond the parent Conte center.

## Key facts

- **NIH application ID:** 10200527
- **Project number:** 3P50MH094271-08S1
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Takao K Hensch
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,250
- **Award type:** 3
- **Project period:** 2020-07-16 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200527

## Citation

> US National Institutes of Health, RePORTER application 10200527, Developmental origins of mental illness: evolution and reversibility (3P50MH094271-08S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10200527. Licensed CC0.

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