# Role of orexin/hypocretin circuit in anesthesia and analgesia

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $199,098

## Abstract

Project Summary/Abstract
With the long-term research goal of advancing anesthesia through developing new tools and techniques for
better anesthetic management and pain control, the candidate focuses his research on elucidating the
mechanisms underlying anesthesia, in particular, the role of hypothalamic orexin (Ox) circuit in anesthesia and
analgesia. How anesthetics interact with brain neural network is still poorly understood. The Ox circuit is
considered to be a master regulator in sleep/wakefulness. The candidate's recent work showed that activation
of Ox neurons with chemogenetic approach facilitates emergence from isoflurane anesthesia and induces
analgesia. Building upon these findings, he proposes to apply optogenetics to specifically activate subsets of Ox
projections to address the underlying mechanisms. The candidate started with mapping the basic neuroanatomy
of the Ox projections in the mouse brain. In his preliminary work, he mapped out three-dimensional Ox
projections using both confocal and lightsheet microscopy and identified three interesting regions he will focus
on in this proposal. In aim 1, he will test the hypothesis that Ox neurons regulate arousal state during anesthesia
via their projections to basal forebrain (BF) and lateral habenula (LHb). In aim 2, he plans to test the hypothesis
that Ox projections to periaqueductal gray (PAG) contributes to analgesia. While manipulating neuronal activities
with optogenetic tools, the candidate will record electroencephalogram (EEG), image in vivo neural calcium
activities, and test the animal's behavior related to arousal state or pain. The proposed work will lead to the
identification of novel roles of different subsets of Ox projections in anesthesia-related arousal and pain control.
The candidate is currently an Assistant Professor in the Department of Anesthesia and Perioperative Care at the
University of California San Francisco (UCSF). His career goal is to become an independent physician scientist
dedicated to understanding the mechanisms governing anesthesia and bring patient care to the next level with
safer and more efficient anesthesia. The candidate has outstanding institutional support with 75% protected
research time, lab and office space, administrative support, and department funding for a technician and selected
equipment. UCSF is a world-class institute and the candidate has a multidisciplinary mentoring team to guide
his career development. Additionally, he has an extensive didactic plan to take advanced training in the next few
years to further build a solid foundation for his expertise in the research on the role of neural circuits in anesthesia
and analgesia.

## Key facts

- **NIH application ID:** 10651642
- **Project number:** 5K08GM138981-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Wei Zhou
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $199,098
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10651642

## Citation

> US National Institutes of Health, RePORTER application 10651642, Role of orexin/hypocretin circuit in anesthesia and analgesia (5K08GM138981-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10651642. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*