# The Roles of Genetically Distinct Cortical Neuron Types in General-Anesthesia- and Sleep-Induced Slow Waves

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $99,999

## Abstract

Project Summary/Abstract. Reversible loss of consciousness is a crucial part of two major medical fields:
general anesthesia and sleep. General anesthetics and non-rapid-eye-movement (NREM) sleep both induce
slow waves (0.1-4 Hz) in the cortical electroencephalogram (EEG). It is unknown whether slow waves generated
with different anesthetic agents and during NREM sleep are generated with the same neural circuit activity. Dr.
Melonakos’ preliminary data suggests that anesthetic agents with different molecular targets have distinct slow
wave mechanisms (Aim 1 Hypothesis). In addition, although dexmedetomidine anesthesia shares neural circuits
with NREM sleep, it may also have distinct direct cortical effects, possibly leading to different slow wave activity
(Aim 2 Hypothesis). The purpose of this research is to test these hypotheses by mapping cortical neural activity
with respect to the EEG slow waves of both anesthesia and NREM sleep. In order to do this, Dr. Melonakos will
learn how to perform calcium imaging experiments in freely behaving rodents. He will then record calcium images
from Ca2+/calmodulin-dependent protein kinase IIa-positive (CaMKIIa+), parvalbumin-positive (PV+),
somatostatin-positive (SST+), and vasoactive intestinal peptide-positive (VIP+) cortical neurons during
anesthesia- and sleep-induced slow waves. Propofol, ketamine, and dexmedetomidine anesthesia will be tested.
Dr. Melonakos will then compare the neural activity between the anesthetics and between general anesthesia
and sleep. Finally, he will identify the role of SST+ neurons in slow waves (Aim 3 Hypothesis) by (1) looking at
the activity of cortical neurons following disruption of slow waves by stimulation of the parabrachial nucleus, an
arousal area in the brainstem, and (2) inhibiting SST+ neurons during anesthesia- and sleep-induced slow waves.
During the K99 phase of this project, Dr. Melonakos will be mentored by Drs. Christa Nehs and Emery Brown,
experts in anesthesia and sleep neurocircuitry and faculty at Harvard Medical School, Massachusetts General
Hospital (MGH), and Massachusetts Institute of Technology (MIT). Dr. Melonakos will also collaborate with Drs.
Michael Hasselmo (Boston University), Nancy Kopell (Boston University), and Daniel Aharoni (University of
California, Los Angeles). He will be trained in calcium imaging by Drs. Hasselmo and Aharoni, and statistical
analysis by Dr. Brown. Dr. Kopell will guide Dr. Melonakos as he orients his findings within hypothesized slow
wave mechanisms from the field of computational neuroscience. Dr. Melonakos will also learn optogenetics
stimulation techniques from Dr. Nehs and in a course at MIT. The mentors, collaborators, and other members of
the MGH community will also provide him with professional guidance as he nears independence, including
training in grant writing, peer review, teaching, and the faculty job search. The scientific and professional training
Dr. Melonakos receives will enable him to develop ...

## Key facts

- **NIH application ID:** 10449437
- **Project number:** 1K99GM141450-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Eric David Melonakos
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $99,999
- **Award type:** 1
- **Project period:** 2022-04-11 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449437

## Citation

> US National Institutes of Health, RePORTER application 10449437, The Roles of Genetically Distinct Cortical Neuron Types in General-Anesthesia- and Sleep-Induced Slow Waves (1K99GM141450-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10449437. Licensed CC0.

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