My laboratory is concerned with three areas of research. We focus on the biochemical regulation of sleep. We described the somnogenic actions of many cytokines, and we showed that interleukin-1 (IL1) and tumor necrosis factor (TNF) are involved in physiological sleep regulation. Each of these substances, mRNA and protein levels, vary in brain with the sleep-wake cycle and are affected by sleep deprivation. These substances increase non-rapid eye movement sleep (NREMS). Conversely, if they are inhibited, sleep is inhibited and the sleep rebound after sleep deprivation is also blocked. Mice lacking IL1 or TNF receptors sleep less than normal. All of these substances act in the hypothalamus and other brain areas to promote NREMS. Our second interest deals with sleep and infectious diseases. Bacterial, protozoan, fungal and viral infectious agents greatly alter sleep. In the case of bacteria, we worked out the molecular steps responsible. For example, with gram-positive bacteria, bacterial peptidoglycan (from cell walls) is digested by macrophages, releasing somnogenic muramyl peptides (these are the monomeric building blocks of bacterial cell walls). Muramyl peptides in turn induce enhanced production of cytokines which in turn affect sleep. Currently we are focusing our efforts on the mechanisms involved in influenza virus–induced sleep. In this case, viral double-stranded RNA, released from infected cells, seems responsible for initiating the sleep cascade. A third interest of my laboratory is with sleep function and brain organization as it applies to sleep. In short, we hypothesized that neuronal assemblies are the organizational level within which sleep is initiated and that local sleep at this level is dependent upon prior activity within the local network. Experimental data support these ideas. For instance, TNF expression by neurons is enhanced in the somatosensory cortex if afferent input induced by whisker twitching is increased. Further, individual cortical columns such as somatosensory barrels alternate between functional states, one of which is usually associated with organism sleep, and that sleep-like functional state is induced by TNF.
Work in our laboratory is funded by 3 NIH R01 grants: NS025378, NS031453 and HD036520.