S112 Cellular basis of sleep oscillations

Abstract

Sleep is a dynamic state characterized by oscillations in wide frequency ranges. Orchestration of neuronal activity is probably a key element in the biological function of sleep and, as a consequence, understanding the neuronal generator of sleep rhythms may take us closer to decipher the role of sleep. Here I introduce three approaches to study sleep oscillations (i) recording multiple elements in the neuronal circuit during natural sleep, (ii) pharmacogenetic interaction with the neuronal transmission at a well-defined point of the neuronal circuit, (iii) transient interruption of the sleep oscillations by optogenetic activation of an arousal system. The data largely revolves around sleep spindles, a transient sleep oscillation generated in the thalamocortical circuit via the interaction of excitatory and inhibitory neurons in the thalamus. The data shows a highly stereotyped, finely tuned neuronal activity during this sleep oscillation where the initial state of the network defines the duration of the ensuing events. This activity is based on the peculiar manner of GABAergic transmission in the thalamus which allows rapid alterations of the inhibitory charge in thalamocortical cells based on the firing pattern of their inhibitory inputs. Finally, we show that sleep spindles selectively display great sensitivity to perturbations and can be disrupted even in those cases where stimulations of ascending systems remain subthreshold for arousal. The data is consistent with a highly dynamic, finely tuned system which generates sleep spindles that closely matches the actual needs and reflect the actual state of the forebrain.