Grant: CIHR New Investigator

In developed countries, there is a drastic rise of chronic sleep loss, as exemplified by reduced sleep duration in children and adolescents, and increasing prevalence of insomnia and night work. However, the mechanisms underlying its adverse effects on mental health, vigilance, learning, and mood are poorly understood. It is known that sleepiness increases with the duration of wakefulness. Moreover, the longer the duration of wakefulness, the more intense/deep the subsequent sleep. Recent work supports the involvement of synapses, the functional unit of communication between neuronal cells, in this process. Neuroligin 1 is an adhesion protein binding to other adhesion molecules and holding the two sides of the synapse together. Importantly, this protein controls the type of excitatory synapses that predominates in the brain, which type is also linked to both deleterious effects of sleep loss and sleep intensity regulation. In this project, the contribution of Neuroligin 1 to sleep regulation will be investigated. First, markers of sleep intensity (i.e., brain electrical activity and gene expression) will be evaluated in mice where Neuroligin 1 is absent or decreased. Second, the effect of the duration of time awake on Neuroligin 1 will be examined by measuring gene and protein expression in the mouse brain after sleep deprivation (i.e., preventing sleep for different duration). Lastly, because we observed that Neuroligin 1 expression could be modulated by specific factors driving transcription (i.e., the reading of a gene expressed as a transcript), we will identify the functional DNA sequences within its gene by in vivo (in mice) and in vitro (assays with cells in culture) methodologies. The results of the project will advance our understanding of neuronal functions, and assist in the prevention and in the development of interventions for people suffering from sleep debt accumulation, including age-related disturbances and insomnia.