Sleep and Homelessness
Homelessness is currently one of the largest public health crises facing the Seattle region, and the city is using different strategies to alleviate its impact. We use wrist actigraphy to chronically monitor sleep in people experiencing homelessness in different environments —tent cities, tiny houses, and permanent or overnight shelters— and study the relationship between these environments, sleep quality and other health outcomes. We are also conducting a series of interviews with our study participants, through which we aim to both highlight their experiences and bring greater public awareness to sleep health disparities in homeless populations.
During a protest by people living in “tent city” in Seattle a homeless person puts sleep in perspective
Research Projects
Sleep and Epilepsy
Epilepsies are among the most common neurological disorders globally. Epileptic syndromes are typically associated with sleep disorders but the neural basis for the impaired regulation of sleep is not well understood. We exploit a genetic mouse model of a severe childhood epilepsy, Dravet syndrome, to determine the mechanisms by which a genetic mutation that produces generalized seizures can also induce deficits in the circadian and homeostatic regulation of sleep. Currently, we are exploring both closed-loop electrophysiological approaches and noninvasive circadian behavioral interventions to improve sleep-related symptoms of Dravet syndrome.
Continuous polysomnographic sleep recordings reveal severely disrupted sleep in a Dravet mouse
Wildtype mouse Dravet mouse
Synaptic Remodeling in the suprachiasmatic nucleus
At the core of circadian rhythms is an autonomous transcription/translation feedback loop involving specific clock gene products. In the SCN, cells operate together to amplify these signals in concert to inform the behavior and physiology of the organism. The emergent properties of the SCN neural network arise via poorly understood processes. In collaboration with Fernanda Ceriani (Fundación Instituto Leloir) and Mark Ellisman (UCSD), we are investigating circadian structural remodeling of SCN cells and hypothesize that these changes play a critical role in the central timekeeping mechanism.
VIPergic neurons and their projections are visualized through the expression of cytosolic TdTomato and the use of “clearing'“ techniques. From Neitz et al. (unpublished)
The timing of fearful stimuli entrains circadian rhythms in rodents.
Cyclic fear (purple bar) in the foraging area induces a shift of feeding and foraging activity to the light phase when presented during the dark phase (DF) but not during the light phase (LF). These rhythmic diurnal behaviors are the output of a fear-entrained oscillator as they persist under constant environmental conditions. Bussi et al. (PNAS 2024)
Fear Entrainment
Circadian clocks are entrained by 24-h environmental cycles and this process assures the synchrony of circadian rhythms with the temporal environment. The light-dark cycle is the most prominent cycle entraining circadian systems but other 24-h cycles can entrain them as well. When mice or rats are housed in a cage divided between a safe nest and a foraging area, animals forage and feed during the dark phase. If the foraging area is made dangerous by applying aversive stimuli only during the dark phase, the animals switch their foraging and feeding behavior to the light phase. This diurnal behavior represents the output of a fear-entrained circadian clock. We are currently investigating the location of this clock and the neural circuitry that underlies this entrainment.
Fitting a wrist activity monitor to measure sleep timing in a Toba/Qom participant.
In the Toba/Qom people sleep starts later and is shorter on the nights leading to the full-moon. From Casiraghi et al. (Science Advances 2021)
Searching for Human Ancestral Sleep
Sleep has been central to human life and its 24-h timing likely changed prominently as humans transitioned from hunting-gathering to agricultural to industrial societies that facilitated access to artificial light. We study sleep non-invasively in aboriginal communities in South America that live in pre-industrial habitats and still practice hunting gathering as part of their survival. We are specifically interested in understanding the natural environmental factors that regulate sleep timing and how electric light interferes with this regulation. We discovereed that, hrough mechanisms that we are currently investigating , daily sleep onset and duration are modulated by lunar phase.
Sleep-deprived undergraduate students.
Seasonal changes in the timing of midsleep are predicted by the amount of daylight each student has. In the winter, maximally delayed sleep is associated with minimal exposure to daylight. Each dot represents a single student. From Dunster et al. (J. Pineal Res. 2022).
Sleep in University Students
University students are typically sleep-deprived. This chronic sleep deprivation is in part due to a misalignment between their social and internal clocks. We non-invasively study sleep habits in undergraduate students, and examine what the critical environmental modulators of sleep are. We found that despite the strict class schedule of undergraduate students living in Seattle the main predictor of their sleep timing is their exposure to daylight, leading to striking seasonal changes, and a greatly delayed sleep bout during the winter.
The Role of GABA in SCN Function
Nearly every neuron in the suprachiasmatic nucleus (SCN), the master circadian clock located in the mammalian hypothalamus, contains the neurotransmitter GABA. While a great deal of evidence suggests GABA is critical to SCN network synchrony, there is still controversy over exactly what role GABA serves in SCN function. We are using genetic approaches to investigate how GABA affects SCN network properties and circadian behavior in the mouse.
Mice lacking expression of the GABA transporter Vgat in Nms-expressing neurons (Nms-Vgat-/-) show severely disrupted rhythms upon release into constant conditions. From Bussi et al. (PNAS 2023)
A raster plot of sleep bouts in a mouse experiencing phase shifts simulating jet lag. From Sanchez et al. (Sleep 2019)
Novel Analysis Methods for Circadian and Sleep Data
The study of circadian rhythms requires investigators to conduct months-long experiments, generating large and often unwieldy time series data. This problem is especially prevalent in the study of the circadian regulation of sleep, which requires long-term continuous recordings of electroencephalography (EEG) and electromyography (EMG) signals, and produces data that is laborious and error-prone to analyze. Surprisingly, few reliable software packages for the automatically scoring sleep stages exist, and the ones that do are often expensive or unintuitive for researchers without computational skills. We are currently developing machine-learnig-based methods for automatic scoring of sleep stages and seizure detection in rodent studies of sleep. Our goal is to make our software freely available to the circadian and sleep communities so that we can empower more researchers to study the circadian regulation of sleep in health and disease.