Network mechanisms promoting cognitive and social development during sleep

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Why is sleep so important for healthy brain functions in children and adolescents? Sleep is essential for healthy development. Yet, children are sleeping less and less, giving rise to a growing public health concern. Crucial new studies point to increase sleep dysfunctions in children diagnosed with autistic spectrum or learning disorders. As screens are invading our kids’ bedroom, there is an urgent need to understand whether and how insufficient sleep during critical developmental windows can be detrimental to healthy cognitive functioning. Research on this subject has – so far – mostly been conducted by clinical or psychology teams aiming to measure the effect of poor sleep on school grades for example. Yet, such methods fail to address the underlying neural mechanisms that can only be manipulated in animal models. To tackle this major gap in our knowledge, I propose to combine cutting-edge in vivo electrophysiology and computational analyses with recent advances in viral and molecular tools to automatically (i) detect and (ii) manipulate sleep states or associated network-mechanisms. I will then (iii) assess how such manipulations may impact cognitive and social development, as well as the underlying neural network maturation. Espepecially, thinking of antidepressant use in mothers.

This research has the ambition to answer a timely health concern. As such, it has a strong potential to have an important societal impact, notably by giving incentive to change policies that encourage healthy sleep habits, as well as translational research applications to explore new therapeutics linked to sleep regulation for patients diagnosed with neurodevelopmental or learning disorders.

We are planning to conduct these experiments on Long Evans. I have over 15 year of experience conducting experiments similar to these described in this proposal. Based on that experience, I estimate that we would need between 15-20 pups (5 litters) per developmental time point and condition. That would amount to approximately 630 pups (= 120 litters) divided between 4-5 researchers. We base our estimates on (i) careful selection of experimental units and power analyses, (ii) minimisation of inter- and intra- individual variability, (iii) careful experimental design (including use of each animal to its full statistic potential with repeated measures) and (iv) minimization of animal loss.

Animal will be pre-handled and used to the experimenter before procedures in order to minimize stress. Surgeries will be conducted under the use of general anaesthesia and analgesics while assuring that temperature and hydration are maintained, and surgery time kept to the minimum. Pups will be transferred to recovery chambers before being return to the family unit. Post-operative care will be provided to minimize pain linked to wound healing. Enriched housing will be provided to minimize stress to the pups or their parents. During the experiments, animals will be either freely-behaving, performing cognitive tests or sleeping in behavioural boxes in order to assess cognitive performances and neural activity. Our experiments depend on the animals neither being in pain nor stressed. If for any reason one animal seems in distress, it will be terminated immediately.