Study of layer 6b, an orexin-sensitive layer in the cerebral cortex
This project represents the continuation of a program to understand the mechanisms by which the hypothalamic neuropeptide orexin influences sleep/wake states. Deficit in this neuropeptide is known to produce sleep disorder narcolepsy, an inability to maintain waking, in both animals and humans.
Numerous studies, including from our laboratory, have suggested that orexin neurons exert their influence by their widespread excitatory projections upon the classical arousal systems that express noradrenaline, serotonin, acetylcholine and histamine as neurotransmitters. While this might indeed be partially true, it is noteworthy that lesioning experiments on these systems have failed to reproduce a narcoleptic phenotype.
Other projections of the orexin system might play a more fundamental role in this respect and we recently found that orexin exerts a powerful excitatory action on a thin cell layer at the bottom of the cortex, layer 6b. Given the pattern of connectivity of this seldom studied layer, we suggest that it could play a role as a diffuse cortical activating system.
Our goal, using a combination of techniques, is to study the neurons of layer 6b, their electrophysiological properties, their response to neurotransmitters, their morphological aspect, the transmitters they express, the extent of their projection. We will in particular focus on those cells which are sensitive to orexin. Our underlying hypothesis are first, that during the post natal days orexin could act like acetylcholine and promote synchronized activity and second, that in adult cortical networks, orexin could preserve some of this capacity and could contribute to cortical activation and the maintenance of the waking state. These studies are expected to shed light on the mechanisms by which sleep/wake states are regulated.