The role of the murine cortex in sleep
File(s)
Author(s)
Giannos, Panagiotis
Type
Thesis
Abstract
The ability of animals to adapt their behaviour in response to a variety of conditions, including internal states, is largely dependent on the prefrontal cortex (PFC). The experience of "tiredness" is a widespread, yet unexplored, internal state. In this study, through the use of activity tagging, we discovered a population of highly excitable, fast-spiking neurons that express γ-aminobutyric acid (GABA) and somatostatin (PFC Sst-GABA) in the mouse PFC. These neurons became particularly active when the mice were deprived of sleep and as a result of homeostatic sleep pressure. Both the lateral hypothalamus (LH) and the lateral preoptic (LPO) hypothalamus received projections from these neurons. Through the use of optogentics and chemogenetics, nesting, increased theta brain wave activity and higher body temperature were examples of sleep preparation behaviours triggered by activation of PFC Sst-GABA neuron terminals in the LPO hypothalamus. Conversely, activating their terminals in the LH induced recovery sleep, which included characteristics such as reduced body temperature, non-rapid eye movement (NREM) sleep and enhanced delta power. PFC Sst-GABA terminals were also preferentially more active in either during nesting and sleep and used postsynaptic currents to inhibit an array of cells in the LPO hypothalamus and LH. Lastly, lesioning of these neurons disrupted NREM sleep and induced wakefulness, while silencing of the Sst gene attenuated delta power. Taken together, these findings suggest that PFC Sst-GABA may play an important role in allowing the PFC to instruct the hypothalamus to transform homeostatic sleep pressure into behaviour that precedes sleep and finally, sleep itself. From an ethological standpoint, the PFC may act to assure the animal's safety prior sleep and thus, enabling survival in the wild.
Version
Open Access
Date Issued
2024-10-11
Date Awarded
01/01/2025
Advisor
Wisden, William
Franks, Nicholas
Sponsor
Bodossaki Foundation
Publisher Department
Department of Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)