# Electrical connectomics: an innovative approach for dissecting brain mechanisms underlying behavioral states

> **NIH NIH DP2** · UNIVERSITY OF IOWA · 2020 · $2,317,500

## Abstract

Project Summary:
Understanding the mechanisms by which the brain encodes behavior presents a major challenge
for developing effective therapies with which to treat neurological and psychiatric disorders. The
development of brain-wide measurements of neural connectivity in mammalian models holds
great potential for overcoming this challenge. Here we propose an innovative approach for
collecting and integrating such data across an unprecedented number of interconnected brain
regions for use in elucidating the mechanisms by which sensory processing is altered in disease.
A number of neurological and psychiatric disorders are triggered or exacerbated by sensory
stimuli, yet little is understood about the brain connectivity underlying such sensory hyper/hypo-
sensitization. Sensory processing plays a major role in the pathology of: autism spectrum
disorders (ASD), schizophrenia, fibromyalgia, attention deficit hyperactivity disorder (ADHD),
sensory perception disorders (SPDs), and migraine. Migraine in particular represents a
compelling model of sensory hypersensitization, as the response to sensory stimuli is clear, dose-
dependent, and measurable. Using state-of-the-art, multi-site in vivo recordings in a well-
characterized migraine model, coupled with machine learning, we will develop network-wide
electrical maps of the sensory hypersensitivity that underlies migraine. These networks will be
validated for their roles in migraine using multiple behavioral assays and migraine-related
pharmacological manipulations. We will additionally dissect the mechanisms underlying the
sensory hypersensitivity brain state in a mouse model of migraine using optogenetic circuit
manipulations as well as single-cell RNA-Seq, with the aim of identifying the contributions of
specific circuits, cells, and molecules to this state. This approach is expected to substantially
facilitate the use of neural oscillation-based brain networks in biomedical research, as well as
provide: 1) a tool for rapid identification of a sensory hypersensitive brain state that can be tested
for mechanisms shared across disorders, 2) a map of features of electrical brain networks, which
serve as strong hypotheses regarding the routes whereby sensory hypersensitivity brain networks
are regulated, and 3) insight into the contributions of specific cell types and molecules to the
hypersensitive brain state. Collectively, this study is expected to provide insights into the etiology
of migraine and other sensory hypersensitivity disorders that will be critical to developing brain
network-based therapies for these diseases.

## Key facts

- **NIH application ID:** 10001808
- **Project number:** 1DP2MH126377-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Rainbo Hultman
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,317,500
- **Award type:** 1
- **Project period:** 2020-09-07 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001808

## Citation

> US National Institutes of Health, RePORTER application 10001808, Electrical connectomics: an innovative approach for dissecting brain mechanisms underlying behavioral states (1DP2MH126377-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001808. Licensed CC0.

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