The thalamus is a brain nucleus that acts as a central relay for transmitting sensory information (with the exception of smell) to the cerebral cortex. Photo: Life Science Databases (LSDB).
Neurobiologists uncover part of the neural mechanism responsible for the long, deep sleep that compensates for sleep deprivation.
The restorative, deep sleep that follows sleep deprivation is initiated by a small group of neurons in the thalamus. That is the conclusion of American neurobiologists writing on 20 June in Science, based on research in mice. As sleep deprivation accumulates, the connection between two small brain regions appears to strengthen – ultimately driving deeper sleep.
The neurobiologists first identified a group of neurons in the so-called nucleus reuniens, a subdivision of the thalamus. This brain region integrates various inputs and determines whether or not to relay them. Optogenetic activation of these nucleus reuniens neurons has a striking effect: initially, mice display more nesting and grooming behaviour, as though preparing for sleep. The sleep that eventually follows lasts longer than normal and is deeper – resembling the restorative sleep by which the body ordinarily tries to offset sleep deprivation. When the researchers blocked the activity of nucleus reuniens neurons whilst the mice were being kept awake, the recovery sleep that followed was far less effective: it was shorter and less deep.
Signals
The nucleus reuniens neurons do not directly promote sleep themselves – if they did, they would be active during sleep. Instead, they turn out to fire more strongly as sleep deprivation builds. In doing so, they send signals towards the zona incerta, a small brain region situated adjacent to the thalamus. The connection between the nucleus reuniens and the zona incerta appears to be the crux of the matter. As sleep deprivation increases, changes emerge in the connections between these regions: more projections appear, along with more synaptic terminals, making it easier for signals to be exchanged. The connection between the nucleus reuniens and the zona incerta thus becomes stronger – and this scales with the degree of sleep deprivation: the more severe the deficit, the stronger the connection. The researchers argue that this process therefore constitutes a kind of biomarker for sleep deprivation. The protein CaMK2 plays a role in these altered connections; when researchers blocked the activity of this protein, fewer changes occurred, and the resulting recovery sleep was also less effective. Precisely what mechanism underlies this remains unclear for now. The neurobiologists also do not yet understand how the nucleus reuniens initially ‘knows’ that sleep deprivation has occurred. Nevertheless, they regard their study as an important step – a view endorsed by American neurobiologists Nichole Gilette and Jonathan Lipton in an accompanying perspective in Science: ‘Many neurological disorders (…) are associated with sleep deprivation (…). Identifying the underlying brain mechanisms may therefore have significant implications for therapeutic applications.’