The thalamus is an important center in sensory and motor integration during wakefulness. In the few species that have been examined, neurons of the thalamus express profound alterations in activity with changes in state of arousal. The mechanisms and functional significance of these state-related alterations are not completely understood. The mouse is a species that has not been studied with respect to thalamic activity and the sleep/wake cycle. A major goal of this proposal is to characterize a mouse model of thalamic activity and its dependence on sleep and wakefulness as well as circadian influences. A mouse model of thalamic activity will allow an expanded comparative approach to species differences and similarities in mechanism and in function. In addition, the model will permit the study of thalamic activity in mouse strains in which gene targeting technology has resulted in specific genetic alterations. Recent application of this technology to traditional animal behavior studies has made major advances in several areas and holds the same promise for investigations of sleep/wake behavior. We have generated a mouse strain deficient in expression of the voltage-gated potassium (K+) channel Kv3.1. This channel protein is highly expressed in neurons of the thalamic reticular nucleus, neurons important to intrathalamic interactions. The role of this ion channel and its control over repolarization of the action potential will be determined by monitoring single cell activity in three thalamic neuronal populations and assessing differences between mouse strains that do and do not express Kv3.1 K+ channels. Data forthcoming from these studies will identify the role of a single gene product in the expression of sleep/wake behavior and will yield a better understanding of the mechanisms at the cellular level. A valuable byproduct of this work will assist in providing rational interventions in disease states such as epilepsy when there is a failure of these mechanisms.
| Espinosa, Felipe; Torres-Vega, Miguel A; Marks, Gerald A et al. (2008) Ablation of Kv3.1 and Kv3.3 potassium channels disrupts thalamocortical oscillations in vitro and in vivo. J Neurosci 28:5570-81 |
| Joho, Rolf H; Marks, Gerald A; Espinosa, Felipe (2006) Kv3 potassium channels control the duration of different arousal states by distinct stochastic and clock-like mechanisms. Eur J Neurosci 23:1567-74 |
| Espinosa, F; Marks, G; Heintz, N et al. (2004) Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels. Genes Brain Behav 3:90-100 |
