How does sleep work?
This fundamental question has been under investigation for several centuries. It is not until recent technological developments (e.g., chemogenetics, optogenetics...) combined with classical EEG measures that we could causally define discrete sleep/wake circuits with any precision. Indeed, in the past few years, investigation of neural control of sleep and wakefulness has ramped up significantly.
I aim to take advantage of these newly developed tools to (1) uncover novel sleep/wake circuitry, (2) understand the functional heterogeneity of these circuits, and (3) use this knowledge to develop new targets for the treatment of sleep and psychiatric disorders.
I've started by completing population-level calcium imaging (using fiber photometry) in a cell type specific manner in the hypothalamus (see below).
The hypothalamus regulates fundamental aspects of behavior, including sleep/wake cycles, thirst and hunger, reproduction, and body temperature, among others. It is a highly heterogenous structure composed of several nuclei with distinct functions. A large population of cells within the lateral hypothalamus are neurons that produce the fast inhibitory neurotransmitter GABA. Using mice that express Cre under the vesicular GABA transporter (VGAT) promoter allows us to specifically manipulate them and understand their function.
After investigating how these neurons operate in relation to sleep/wake cycles, their causal role in promoting arousal can be tested with optogenetics (see image below). In the future I aim to uncover the functional heterogeneity of these neurons (as they are made up of many different subpopulations), and use these data to inform computational models of sleep/wake regulation.
Banner Image: hM4Di-mCherry, RFP-Alexa488, DAPI in lateral hypothalamus.
All rights reserved: Jeremy Borniger, PhD