Sleep seems simple enough, a state of rest and restoration that almost every vertebrate creature must enter regularly in order to survive. But the brain responds differently to stimuli when asleep than when awake, and it is not clear what brain changes happen during sleep. “It is the same brain, same neurons and similar requirements for oxygen and so on, so what is the difference between these two states?” asks Rodolfo Llinás, a professor of Neuroscience at New York University School of Medicine and a Whitman Center Investigator at the Marine Biological Laboratory (MBL) in Woods Hole. In a recent paper, Choi, Yu, Lee, and Llinás announced that a specific calcium channel plays a crucial role in healthy sleep, a key step toward understanding both normal and abnormal waking brain functions.
To tackle the broad question of sleep, Llinás and his colleagues focused on one crucial part of the puzzle in mice. Calcium channels, selective gates in neuron walls, are integral in neuron firing, ensuring that all parts of the brain keep talking to one other. But during sleep, calcium channel activity is increased, keeping a slow rhythm that is different from patterns found during wakefulness. Based on this clue, the scientists removed one type of calcium channel, Cav3.1, and looked at how the absence of that channel’s activity affected mouse brain function.
This calcium channel turns out to be a key player in normal sleep. The mice without working Cav3.1 calcium channels took longer to fall asleep than normal mice, and stayed asleep for much shorter periods. “They basically took cat naps,” says Llinás. Their brain activity was also abnormal, more like normal wakefulness than sleep. Most importantly, these mice never reached deep, slow-wave sleep. “This means that we have discovered that Cav3.1 is the channel that ultimately supports deep sleep,” Llinás says.
Because these mice completely lack the ability to sleep deeply, they eventually express a syndrome similar to psychiatric disorders in humans. Llinás believes that studying how the brain functions during unconsciousness is key to understanding normal consciousness, as well as abnormal brain activity. This paper begins to uncover one of the key mechanisms of normal sleep, as well as the role for one important calcium channel in overall brain function.
Funding: The research was supported by the National Institute of Neurological Disorders and Stroke.
Source: Diana Kenney – MBL
Image Credit: Image credited to Database Center for Life Science and is licensed Creative Commons Attribution 3.0 Unported
Original Research: Abstract for “Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness” by Soonwook Choi, Eunah Yu, Seongwon Lee, and Rodolfo R. Llinás in PNAS. Published online June 26 2015 doi:10.1073/pnas.1420983112
Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness
In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states.
“Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness” by Soonwook Choi, Eunah Yu, Seongwon Lee, and Rodolfo R. Llinás in PNAS. Published online June 26 2015 doi:10.1073/pnas.1420983112