Ablation of Kv3.1 and Kv3.3 potassium channels disrupts thalamocortical oscillations in vitro and in vivo.
The genes Kcnc1 and Kcnc3 encode the subunits for the fast-activating/fast-deactivating, voltage-gated potassium channels Kv3.1 and Kv3.3, which are expressed in several brain regions known to be involved in the regulation of the sleep-wake cycle. When these genes are genetically eliminated, Kv3.1/Kv3.3-deficient mice display severe sleep loss as a result of unstable slow-wave sleep. Within the thalamocortical circuitry, Kv3.1 and Kv3.3 subunits are highly expressed in the thalamic reticular nucleus (TRN), which is thought to act as a pacemaker at sleep onset and to be involved in slow oscillatory activity (spindle waves) during slow-wave sleep. We showed that in cortical electroencephalographic recordings of freely moving Kv3.1/Kv3.3-deficient mice, spectral power is reduced up to 70% at frequencies <15 Hz. In addition, the number of sleep spindles in vivo as well as rhythmic rebound firing of TRN neurons in vitro is diminished in mutant mice. Kv3.1/Kv3.3-deficient TRN neurons studied in vitro show approximately 60% increase in action potential duration and a reduction in high-frequency firing after depolarizing current injections and during rebound burst firing. The results support the hypothesis that altered electrophysiological properties of TRN neurons contribute to the reduced EEG power at slow frequencies in the thalamocortical network of Kv3-deficient mice.
Espinosa
Felipe
F
Departments of Neuroscience and Psychiatry, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9111, USA.
Torres-Vega
Miguel A
MA
Marks
Gerald A
GA
Joho
Rolf H
RH
D000109:Acetylcholine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001683:Biological Clocks / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D004569:Electroencephalography; D004576:Electromyography; D005583:Fourier Analysis; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology; D017286:Polysomnography; D051670:Shaw Potassium Channels / Q000172:deficiency*; D012892:Sleep Deprivation; D013787:Thalamic Nuclei / Q000502:physiology*
D015306:Biogenic Monoamines; C085724:Kcnc3 protein, mouse; D051670:Shaw Potassium Channels; D000109:Acetylcholine