Aurélie BRECIER defense of thesis - State-dependent activity of cortical inhibitory neurons during the sleep-wake cycle

Abstract

During the sleep-wake cycle, our brain must maintain a balance between excitation and inhibition in order to operate effectively. In the neocortex, inhibition is mainly subtended by parvalbumin (PV), somatostatin (SST) and intestinal vasoactive peptide (VIP) neurons. However, the involvement of these interneurons during sleep remains poorly understood.
The first objective of my thesis was therefore to characterize interneurons activity throughout the sleep/wake cycle. Targeted in vivo recordings of genetically-identified GABAergic inhibitory cells in the barrel cortex of naturally-sleeping, head-restrained mice revealed an increase in activity of PV cells in NREM and REM sleep, a modification of pattern discharge of SST neurons in NREM sleep and an activation of VIP cells during REM sleep. In addition, interneuronal activity was also modulated by specific sleep oscillations such as spindles, delta and theta rhythms.
In a second part, we hypothesized that the integration of sensory information at the level of the cortex during sleep could be modulated by the dynamic interneuronal activity that we had observed. In order to investigate this, we applied small passive whisker deflections during the different states of vigilance. Surprisingly, our results indicate that all of the actors of the excitation-inhibition balance respond with greater intensity to stimulation occurring during NREM sleep.
In summary, this thesis provides a better understanding of how the balance between excitation and inhibition can be dynamically maintained in fundamentally different states of vigilance while allowing the local cortical somatosensory circuit to integrate and process incoming sensory and cortico-cortical information in a sleep stage-specific manner.

Key words: GABAergic interneurons, sleep, excitation-inhibition balance, sensory integration, cortical oscillations, primary somatosensory cortex, whiskers