# Look inward: brainstem and cortical circuits for boosting interoceptive attention

> **NIH NIH DP1** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $1,225,000

## Abstract

Project Summary/Abstract
A vast effort to examine peripheral and central brain circuits underlying external senses such as vision,
hearing and touch hearing has yielded broad insights and fueled development of diverse sensory rehabilitation
therapies. In contrast, a similar mechanistic understanding of how the brain receives and attends to signals
from inside the body is sorely lacking. This is surprising given the growing awareness of the central roles of
body-brain communication in a broad range of diseases spanning neurology, psychiatry, and general medicine
(e.g. depression and anxiety disorders; autism spectrum disorder; sickness behaviors during peripheral states
of infection/inflammation such as fatigue, decrease consumption, social isolation, and anhedonia; eating
disorders and obesity; cardiovascular diseases, gastrointestinal diseases, sleep apnea and other respiratory
disorders, itch, acute and chronic pain, irritable bowel syndrome, and natural and chemotherapy-induced
nausea and vomiting). A roadmap of the specific circuits governing our perception and selective attention to
these body signals could give rise to a host of precisely targeted clinical therapies. However, major
technological challenges have limited the possibility of well-controlled studies of internal sensation,
perception and attention in animal models. Here, I propose to overcome these technical barriers to
establish a platform that will enable our lab and others to gain a detailed circuit-level understanding of
interoception – the process of attending to and perceiving internal bodily signals – and how this
process is disrupted across a range of diseases. I will use my expertise in innovating new strategies for
studying the circuit-level basis of visual, auditory and tactile perception to develop a multi-level platform for
studying interoception in behaving mice. In particular, we will overcome the following key challenges. First, we
will develop a novel operant behavioral paradigm in which head-restrained mice learn to report specific
threshold-level body signals. To accurately measure thresholds for perception of specific body signals, we will
optogenetically stimulate specific genetically-defined sets of vagal afferent neurons that relay signals from
specific body organs (e.g. lung stretch or gut nutrient signals) to the brain. By stimulating at various intensities,
we will estimate interoceptive perceptual thresholds, how these thresholds improve with learning (similar to
mindfulness and meditation training) and how they worsen in the presence of competing external stimuli (e.g.
a flashing cell phone). We will then begin to dissect the neural circuits that gate central processing of specific
vagal signals. To this end, we will combine the above behaviors with new approaches for optogenetic
manipulation and two-photon calcium imaging of (i) central terminals of vagal afferents, (ii) brainstem
serotonergic inputs to regulating vagal afferent transmission and (iii)...

## Key facts

- **NIH application ID:** 10019465
- **Project number:** 5DP1AT010971-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Mark L Andermann
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,225,000
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019465

## Citation

> US National Institutes of Health, RePORTER application 10019465, Look inward: brainstem and cortical circuits for boosting interoceptive attention (5DP1AT010971-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10019465. Licensed CC0.

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