# The Anesthetic Circuitry of the Midbrain

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $368,137

## Abstract

PROJECT SUMMARY/ABSTRACT
 Every day approximately 100,000 people undergo general anesthesia in the United States, and by the
age of 70, almost all of us will experience general anesthesia. Yet it remains unknown how anesthetics
produce unconsciousness, and how consciousness is restored after general anesthesia. The broad, long-
term objectives of this project are to: (1) make general anesthesia safer by developing new ways to restore
consciousness and cognition in anesthetized patients, and (2) aid the development of safer anesthetics by
elucidating the mechanisms of anesthetic-induced unconsciousness. In our application we show that midbrain
GABA neurons in the rostromedial tegmental nucleus (RMTg) are involved in anesthetic-induced
unconsciousness, while midbrain dopamine neurons in the ventral tegmental area (VTA) are involved in
emergence and cognitive recovery from general anesthesia. The Specific Aims are to: (1) characterize the
role of the RMTg-VTA circuit in anesthetic-induced unconsciousness, (2) characterize the role of VTA
dopamine neurons and their projections in anesthetic emergence, and (3) identify the VTA dopaminergic
projections that promote cognitive recovery from the anesthetized state, using a touchscreen-based visual
discrimination task. Using genetically modified rodents that allow for selective targeting of dopamine and GABA
neurons, we will employ a combination of optogenetics, chemogenetics, neurophysiological recordings, and
touchscreen cognitive testing to elucidate the anesthetic circuitry of the midbrain. This project will shed light on
fundamental mechanisms of anesthesia and consciousness, which will allow us to improve patient care by
developing new techniques to help the brain recover from general anesthesia. In addition, this work will
facilitate the development of new anesthetics with fewer side effects.

## Key facts

- **NIH application ID:** 9850268
- **Project number:** 5R01GM126155-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Ken Solt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,137
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850268

## Citation

> US National Institutes of Health, RePORTER application 9850268, The Anesthetic Circuitry of the Midbrain (5R01GM126155-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850268. Licensed CC0.

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