Slow wave activity (SWA; 0.5-4.0 Hz) in the sleep electroencephalogram is a marker of sleep need,increasing with the duration of prior wakefulness and decreasing exponentially during sleep. The biologicalprocess responsible for the increase of SWA as a function of prior wakefulness, however, remains unknown.According to a recent hypothesis - the synaptic homeostasis hypothesis of sleep function - plastic processesoccurring during wakefulness result in a net increase in synaptic strength in many cortical circuits. As aconsequence, when cortical neurons begin oscillating at low frequencies during sleep, they become stronglysynchronized, leading to slow waves of high amplitude and thereby to increased SWA. These slow waves, inturn, are responsible for the renormalization of synaptic strength and have beneficial effects on energymetabolism and performance. Recent work has shown that, consistent with the hypothesis, wakefulness isassociated with the induction of genes involved in synaptic potentiation, such as Arc, BDNF, P-CREB, andNGFI-A, while sleep is associated with higher expression of genes involved in synaptic depression, such ascalcineurin and NSF. Building upon these results, this Project will examine specific molecular markers ofsynaptic potentiation/depression in parallel with local field potential recordings of SWA in freely behavingrats.
Aim 1 will quantify synaptic AMPA receptor number and phosphorylation state in wakefulness and sleepto confirm the prediction that the former is associated with synaptic potentiation and the latter with synapticdepression.
Aim 2 will test the prediction that sleep SWA will be higher, for the same amount of wakefulness,if markers of synaptic potentiation are induced at higher levels through increased exploratory activity.
Aim 3 will employ a forelimb motor learning task inspired by the human learning task used in Projects II, III, and IVto test the prediction that local molecular changes associated with synaptic potentiation are associated with alocal increase in SWA homeostasis in rat contralateral motor cortex. Thus, this Project will provide themolecular / electrophysiological underpinning for the entire proposal.
Showing the most recent 10 out of 67 publications