# Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System

> **NIH NIH OT2** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $2,717,567

## Abstract

ABSTRACT
The colon is the site of a multitude of disorders which are leading causes of morbidity and mortality and of
significant financial burden. The colonic intrinsic (enteric) and extrinsic innervation play crucial role in regulating
the secreto-motor, endocrine, immune functions and pain sensation. There has been increasing understanding
of the neurochemical and electrophysiological properties, cell physiology, and functional roles of colonic enteric
neurons and their interaction with the parasympathetic, sympathetic and sensory systems during the past
decades. However, these data are derived largely from small animal studies and relevant knowledge in large
animals and humans is lagging, which has hampered the development of effective therapies. Recent advances
in cutting edge approaches including 3-D mapping, innovative viral tracing tools, and neuroimaging provide a
means to obtain detailed information on neural circuits and related functions in large animals and human tissues,
which has never been achieved before. The overall objective of the proposal is to provide a comprehensive and
detailed structural and functional mapping of the intrinsic and extrinsic innervation of various regions of the colon
in humans and the pig, as a relevant large animal model based on its structural and physiological similarities to
humans. Mice will be utilized for studies involving transgenic, optogenetics and viral tracing approaches. This
objective will be achieved by a concerted effort of world expert investigators who developed state-of-the art
neuroanatomical, molecular, electrophysiological and functional approaches. Preliminary data obtained by the
consortium team showed the feasibility to use CLARITY, high resolution confocal microscopy, viral tracing and
optogenetics to provide detailed mapping of extrinsic nerve fibers, enteric circuitries and the expertise to probe
human colonic enteric neurons electrophysiologically by fast and high resolution neuroimaging. In addition, the
design of new microelectrode array and fiber optic technology has allowed quantifying motor patterns in response
to nerve stimulation at a resolution level not attained before. The combined effort and multidisciplinary
approaches will fill the gaps in current knowledge on colonic intrinsic and extrinsic neuronal circuits and cell-cell
communication, especially in human tissues and pig, a large animal model ideally suited for translational
applicability to patients. These findings will set the foundation for understanding neurocircuitry in this organ and
will be critical for potential electroceutical interventions to treat colonic disorders.

## Key facts

- **NIH application ID:** 10243246
- **Project number:** 3OT2OD024899-01S4
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** MILLION MULUGETA
- **Activity code:** OT2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,717,567
- **Award type:** 3
- **Project period:** 2017-09-16 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10243246

## Citation

> US National Institutes of Health, RePORTER application 10243246, Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System (3OT2OD024899-01S4). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10243246. Licensed CC0.

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