# The neurobiology of global state transitions

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $45,520

## Abstract

Project Summary
Sleep has long fascinated scientists and philosophers alike. To date, the sleep field has made enormous
strides towards explaining how the activity patterns recorded during sleep stages are generated. However, the
transitions between wakefulness and sleep and between the stages of sleep are understudied. Sleep and
wake promoting neuronal populations exhibit self-excitation and mutual inhibition12–16 which is thought to give
rise to a winner-take-all strategy.17,18 This has typically been assumed to mean states of wake and sleep
cannot coexist in the brain. However, from several specialized classes of species that engage in uni-
hemispheric sleep, we know it is possible for part of the brain to fall asleep while another remains
awake.18,19,21,22 During local sleep episodes recorded in rats, spatially restricted pockets of cortical tissue
entered a slow wave rhythm of activity during behavioral wakefulness.23 Our lab and others have demonstrated
that activity in the cortex undergoes state transitions during general anesthesia as well.27,28 What remains
unknown is whether local state transitions are a general mechanism for transitions between consciousness
and unconsciousness or if they are specific to sleep deprivation. I hypothesize that local state transitions
are, in fact, a general mechanism, and, furthermore, that all global state transitions are initiated locally
and propagated through the cortex. In Aim 1, I will use general anesthesia. General anesthesia and sleep
are not the same, but they do share common circuitry within the brain.30-32 Preliminary data from our lab
suggests that state transitions under anesthesia can be local, however, no attempt has been made to quantify
this observation. In my experiments, I will build upon our published methods to create a continuous measure of
brain state independently for each channel of a 3D array of electrodes. In this way, I will be able to identify the
initiation of state transitions and track propagation. In Aim 2, I will use the same methods to define brain states
and transitions in recordings of natural sleep and wake in freely behaving animals. By recording from the same
animals with and without sleep deprivation, I will be able to address whether or not local sleep is specific to
sleep deprivation. Collectively, the data collected will allow me to directly address the question of whether local
state transitions are a general mechanism that spread to give rise to global state transitions. Regardless of
whether sleep and anesthesia show that same results, it is essential to define transitions using the same
methodology for comparison and interpretation. My results will have the potential to revolutionize the way the
field thinks about sleep and anesthesia which could have profound implication for human patients who suffer
from sleep disorders in which they struggle to initiate or maintain natural sleep or the millions of yearly surgical
patients. This grant will provide indisp...

## Key facts

- **NIH application ID:** 10151358
- **Project number:** 1F31NS118808-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Brenna Shortal
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151358

## Citation

> US National Institutes of Health, RePORTER application 10151358, The neurobiology of global state transitions (1F31NS118808-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10151358. Licensed CC0.

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