# Imaging Cortical Circuitry During General Anesthesia-Induced Analgesia

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $68,387

## Abstract

PROJECT SUMMARY/ABTRACT
General anesthetics work in a concentration-dependent manner on the central nervous system (CNS) to induce
loss of consciousness and block the experience of pain. Despite advances in our understanding of the molecular
mechanisms of general anesthetics, how anesthetics alter CNS functioning to abolish the perception of pain is
not well understood. A major impediment to progress has been a lack of understanding as to how general
anesthetics exert their effects at the circuit level, particularly within regions of the cerebral cortex that process
information relevant to the experience of pain. The processing of sensory stimuli by cortical circuits is tightly
regulated by functionally distinct subpopulations of cortical neurons that have dissociable contributions in
modulating local neural activity and information processing. However, how functionally distinct subpopulations
of cortical neurons contribute to altered network activity during general anesthesia remains largely unexplored.
This proposal aims to address two key questions:
 (1) Are functionally distinct neurons within the cortex (e.g., excitatory versus inhibitory, as well as molecularly
 distinct subclasses of inhibitory interneurons) differentially susceptible to general anesthetics? (Specific
 Aims 1 and 2)
 (2) Which subpopulations of functionally distinct neurons are activated by noxious stimuli, and are these
 responses altered during general anesthesia? (Specific Aim 3)
Using miniature epifluorescent and two-photon calcium imaging to simultaneously monitor the in vivo activity of
hundreds individual neurons within their larger cortical ensembles in the mouse during general anesthesia, this
proposal aims to uncover the mechanisms through which a major volatile anesthetic, isoflurane, produces
analgesia. Genetic approaches will be used to selectively fluorescently label functionally distinct subpopulations
of cortical neurons. To determine whether functionally distinct populations of cortical neurons are differentially
affected by isoflurane anesthesia, neural activity is monitored before, during and after anesthesia to compare
the responses of (1) excitatory versus inhibitory neurons and (2) molecularly distinct subpopulations of inhibitory
interneurons to the overall neuronal population. The responses of these distinct neuronal subpopulations will
then be monitored during an acute, noxious stimulus to determine how isoflurane anesthesia interferes with
cortical circuitry to produce analgesia. These studies are focused on two regions implicated in the generation of
the pain percept: the anterior cingulate (ACC) and primary somatosensory (SI) cortices, which respectively
process the affective and discriminative aspects of pain.

## Key facts

- **NIH application ID:** 9893717
- **Project number:** 5F32GM131479-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jarret A.P. Weinrich
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,387
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893717

## Citation

> US National Institutes of Health, RePORTER application 9893717, Imaging Cortical Circuitry During General Anesthesia-Induced Analgesia (5F32GM131479-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893717. Licensed CC0.

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