With Terrence Sejnowski (Salk Institute, USA), we have elaborated a theory of memory consolidation during sleep. As detailed in Section~\ref{ANAL}, in collaboration with Diego Contreras and Mircea Steriade, we have characterized the spatiotemporal structure of LFP and unit activity during wake and sleep states in the cat [1]. This analysis suggests the deepest phase of slow-wave sleep consists of the alternance between slow-waves and short episodes of "wake-like" activity ("up-states"), which are electrophysiologically almost undistinguishable from the activity during wakefulness. This cyclic structure is consistent with the fact that up-states would represent "replayed" events that have occurred previously during the wake state [1]. Interestingly, during the early phase of slow-wave sleep, another type of oscillation, sleep spindles, seem to be optimal to induce a massive calcium entry in cortical pyramidal neurons [2]. This conclusion was reached by combining computational models with intracellular measurements during spindles in cortex. Such a massive calcium entry, at a frequency around 10 Hz, is an ideal signal to activate molecular gates, such as protein kinase A (PKA). Sleep spindles would therefore provide a physiological signal similar to the repeated tetanus used to induce long-term synaptic changes in slices. However, instead of inducing potentiation directly, spindles may in fact provide a "priming" signal, opening a gate that allows permanent changes to subsequent inputs (the "replayed" events above) following the sleep spindles.
Taking those two observations together leads to the following scenario for how these different mechanisms may contribute to memory consolidation during sleep [3, 4]. During conscious experience, latent memories are formed throughout the cortex, together with links to the hippocampal formation that allow top-down retrieval to occur. During the early stages of sleep, spindle oscillations would mobilize the molecular machinery needed for memory consolidation. In the deeper phases of slow-wave sleep, during the brief periods of wake-like activities ("up-states"), the hippocampal formation would activate latent memories stored in the neocortex ("replay") and induce permanent changes in intrinsic or synaptic conductances. This hypothetical mechanism of memory consolidation during sleep is consistent with all electrophysiological characteristics of sleep oscillations, and it predicts that special correlations between hippocampal and cortical activities should occur during the up-states of slow waves (see details in [4]). Such correlations have been found recently between cortical slow-waves (up states) and hippocampal sharp waves by Buzsaki's and McNaughton's groups. No computational model has been proposed to date to explain these observations, and certainly constitutes one of the most exciting directions to pursue towards exploring the role of sleep oscillations.
[1] Destexhe, A., Contreras, D. and Steriade, M. Spatiotemporal analysis of local field potentials and unit discharges in cat cerebral cortex during natural wake and sleep states. J. Neurosci. 19: 4595-4608, 1999 (see abstract)
[2] Contreras, D., Destexhe, A. and Steriade, M. Intracellular and computational characterization of the intracortical inhibitory control of synchronized thalamic inputs in vivo. J. Neurophysiol. 77: 335-350, 1997 (see abstract)
[3] Sejnowski, T.J. and Destexhe, A. Why do we sleep? Brain Research 886: 208-223, 2000. (see abstract)
[4] Destexhe, A. and Sejnowski, T.J. Thalamocortical Assemblies, Oxford University Press, 2001 (see abstract)
Unité de Neurosciences, Information & Complexité
(UNIC)
CNRS
UPR-3293, Bat 33,
1 Avenue de la Terrasse,
91198 Gif-sur-Yvette, France.
Tel: +33-1-69-82-34-35
Fax: +33-1-69-82-34-27