# Project 4: Mathematical Modeling Studies of Anesthetic Action

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $258,387

## Abstract

PROJECT 4: MODELING STUDIES OF ANESTHETIC ACTION
General anesthesia is a fascinating man-made, neurophysiological phenomenon that has been developed
empirically over many years to enable safe and humane performance of surgical and non-surgical procedures.
Specifically it is a drug-induced condition consisting of unconsciousness, amnesia, analgesia and immobility,
along with physiological stability. General anesthesia is administered daily to 60,000 patients in the United
States, the mechanisms for how anesthetics act in the brain to create the states of anesthesia are not well
understood. Significant progress has been made recently in characterizing the molecular sites that anesthetics
target. However, how actions at specific molecular targets lead to the behavioral states is less well understood.
Addressing this issue requires a systems neuroscience approach to define how actions of the drugs at specific
molecular targets and neural circuits lead to a behavioral state of general anesthesia. In this program project
entitled, Integrated Systems Neuroscience Studies of Anesthesia, we will develop an integrated systems
neuroscience program consisting of human, non-human primate, rodent and modeling studies of four
anesthetics: the GABAA agents, propofol and sevoflurane; the alpha-2 adrenergic agonist, dexmedetomidine;
and the NMDA receptor antagonist, ketamine. The program project will also include a DATA ANALYSIS CORE,
which will provide assistant with data analysis and conduct research on statistical methods. The Specific Aims
are to understand how the actions of the anesthetics at specific molecular targets and neural circuits produce
the oscillatory dynamics (EEG rhythms, changes in LFPs and neural spiking activity) that are likely a primary
common mechanism through which anesthetics create altered states of arousal (sedation, hallucination,
unconsciousness). The goal of the modeling research will be to develop detailed, circuit-level descriptions of
the neurophysiological mechanisms underlying each brain state of each anesthetic. The modeling will provide
a systematic way to organize and integrate information across all of the three experimental projects and
thereby, allow us to develop precise statements about anesthetic mechanisms of action. As the research
proceeds, the modeling will enable us to make predictions that can be tested with experiments. In addition to
providing new insights into the systems neuroscience of anesthetic states, these studies will also provide
fundamental new quantitative knowledge about the neurophysiology of the brain's arousal circuits that will be
relevant to studies of other neuropsychological problems such as coma, pain, sleep and depression.

## Key facts

- **NIH application ID:** 9853815
- **Project number:** 5P01GM118269-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** NANCY KOPELL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $258,387
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853815

## Citation

> US National Institutes of Health, RePORTER application 9853815, Project 4: Mathematical Modeling Studies of Anesthetic Action (5P01GM118269-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9853815. Licensed CC0.

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