The contribution of synaptic adhesion systems to sleep regulation

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In mammals and many non-mammalian species, sleep is essential to life. According to current models, sleep is orchestrated by two mechanisms: a circadian process and a homeostatic process. In mammals, the circadian process originates from the biological clock located in the hypothalamus and generates an about 24-h rhythm in various physiological functions as the rhythmic changes in body temperature and alertness, among many others. The homeostatic process is an hourglass mechanism that regulates sleep intensity according to the duration and quality of prior wakefulness. Its nature has not been clearly defined and the way the processes interact is also unknown. However, recent work supports the involvement of synapses, the functional structure required for the communication between neuronal cells, in the homeostatic process. Synaptic adhesion molecules hold the two sides of the synapse together but, more importantly, these proteins control the strength of the communication between neurons. In this project, the contribution of adhesion systems to sleep regulation will be investigated. First, the markers of the homeostatic process (i.e. brain electrical activity recorded on the surface of the cortex and the expression of specific genes in the brain) will be evaluated after sleep deprivation in mice where specific synaptic adhesion molecules are downregulated using RNA interference. Second, the properties of the circadian timing system (e.g. the synchronization with the light/dark cycle of the environment, the length of the endogenous circadian period in constant darkness and the phase-shift response to light stimulus) will be evaluated in mice in which synaptic molecules are downregulated using RNA interference as well. This project will be achieved by the formation of at least two master students and 5 undergraduate trainees in the next five years. The results of the project will advance our understanding of sleep physiology and neuronal functions, and assist in the development of treatments and interventions for patients suffering from disorders involving disturbance in sleep regulatory processes, including age-related changes and insomnia.