# Brain control of internal organ function

> **NIH NIH DP1** · ALLEN INSTITUTE · 2022 · $1,188,152

## Abstract

Abstract
Adaptive control of behavior is critical for survival. Even a simple movement, like extending the arm, requires
the activation of many neuronal populations across the nervous system. Our lab has used a combination of
anatomical, genetic, optical and behavioral approaches to unravel how animals move, and learn to control
movement. However, adaptive responses are not effected only through muscles, but also through other
organs. For example, planning to pick an apple will trigger not only muscle activity but also the expectation
of food, and the conditioned release of insulin. Hence adaptive behavior requires the coordination of an
organism's actions with its physiological internal states. We propose to leverage our expertise to dissect the
neural circuits and principles governing the learning and adaptive “motor” control of internal organ function.
We will spearhead this new research direction by investigating conditioned insulin release and conditioned
immunosuppression, mediated by the innervation of the pancreas and spleen, respectively. We will leverage
state of the art viral and RNA-seq approaches to map with high-resolution the first, second and third-order
innervation of spleen and pancreas. Our preliminary anatomical mapping of the innervation of these organs
revealed that different populations of celiac-mesenteric ganglia sympathetic neurons innervate pancreas
versus spleen. Remarkably, most innervation of the thoracic preganglionic spinal cord targeting these organs
emerges from the cortex: motor cortex, but also sensory and prefrontal. We therefore hypothesize that
learning to select the appropriate responses in internal organs after conditioning is mediated by higher-order
brain circuits, and follows principles similar to those used for motor responses. We propose to use both
targeted and unbiased approaches to identify and manipulate the activity of descending neural populations
responsible for the learned control of spleen and pancreatic function. This new line of research is innovative
but trackable with our expertise, and the Pioneer award support will help us attack this novel research area.
Importantly, the proposed research has the potential to conceptually position the nervous system as a “smart”
regulator of organism homeostasis, and hence impact health in unexpected ways - mental disorders like
anxiety and depression, or neurological problems like stroke, are associated with abnormal physiological
states likely emerging from these brain-internal organ interactions.

## Key facts

- **NIH application ID:** 10679652
- **Project number:** 7DP1AT011979-02
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Rui M. Costa
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,188,152
- **Award type:** 7
- **Project period:** 2021-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679652

## Citation

> US National Institutes of Health, RePORTER application 10679652, Brain control of internal organ function (7DP1AT011979-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10679652. Licensed CC0.

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