Site‐specific inhibition of the thalamic reticular nucleus induces distinct modulations in sleep architecture

The thalamic reticular nucleus (TRN) is crucial for the modulation of sleep-related oscillations. The caudal and rostral subpopulations of the TRN exert diverse activities, which arise from their interconnectivity with all thalamic nuclei, as well as other brain regions. Despite the recent characterization of the functional and genetic heterogeneity of the TRN, the implications of this heterogeneity for sleep regulation have not been assessed. Here, using a combination of optogenetics and electrophysiology in C57BL/6 mice, we demonstrate that caudal and rostral TRN modulations are associated with changes in cortical alpha and delta oscillations, and have distinct effects on sleep stability. Tonic silencing of the rostral TRN elongates sleep episodes, while tonic silencing of the caudal TRN fragments sleep. Overall, we show evidence of distinct roles exerted by the rostral and caudal TRN in sleep regulation and oscillatory activity

Investigation of neuroanatomical subdivisions of the thalmic reticular nucleus upon brain states

The thalamic reticular nucleus (TRN), a part of the corticothalamic loop, plays a key role in selective attention and sleep spindle generation. Furthermore, sleep spindles are reduced in amplitude and duration in schizophrenia patients, implying clinical relevance of TRN functions. However, while the TRN is topographically organized, it remains unclear whether and how the TRN consists of functionally distinct sub-regions. Combining optogenetic and electrophysiological approaches in mice, we investigated changes in sleeping behavior and EEG oscillations caused by optogenetic stimulations in different parts of the TRN. Two inhibitory opsins Halorhodopsin (Halo) and Archaerhodopsin (Arch) were expressed specifically in either an anterior or posterior part of the TRN in parvalbumin (PV)-Cre mice using adeno-associated viral vectors. Effects of optical stimulation on cortical EEGs were assessed by delivering green light through chronically implanted optic fibers over 30 second periods in freely behaving animals. Tonic stimulations during awake states did not produce any significant change in EEG, whereas the stimulations during sleep significantly affected several frequency bands associated with TRN functions. The delta oscillation was decreased significantly during optogenetic inhibition in the rostral and caudal TRN. The sleep spindles, alpha waves, were significantly diminished only during the caudal TRN inhibition. The rostrally inhibited animals had a tendency for longer sleep and had a reduced proportion of the short sleep episodes relatively to the mice with caudally inhibited TRN. Lastly, we demonstrated that the caudal and rostral TRN are taking part in the brain state transition. The caudal part of the nucleus appears important for the wake - NREM sleep transition and the rostral TRN activation is associated with the sleep-wake transition. Although, it was a basic way to test the hypothesis, we concluded that rostral and caudal TRN consist of distinct subnetworks which have different activity levels during sleep. This is the first known description of TRN heterogeneity based on the location principles.The thalamic reticular nucleus (TRN), a part of the corticothalamic loop, plays a key role in selective attention and sleep spindle generation. Furthermore, sleep spindles are reduced in amplitude and duration in schizophrenia patients, implying clinical relevance of TRN functions. However, while the TRN is topographically organized, it remains unclear whether and how the TRN consists of functionally distinct sub-regions. Combining optogenetic and electrophysiological approaches in mice, we investigated changes in sleeping behavior and EEG oscillations caused by optogenetic stimulations in different parts of the TRN. Two inhibitory opsins Halorhodopsin (Halo) and Archaerhodopsin (Arch) were expressed specifically in either an anterior or posterior part of the TRN in parvalbumin (PV)-Cre mice using adeno-associated viral vectors. Effects of optical stimulation on cortical EEGs were assessed by delivering green light through chronically implanted optic fibers over 30 second periods in freely behaving animals. Tonic stimulations during awake states did not produce any significant change in EEG, whereas the stimulations during sleep significantly affected several frequency bands associated with TRN functions. The delta oscillation was decreased significantly during optogenetic inhibition in the rostral and caudal TRN. The sleep spindles, alpha waves, were significantly diminished only during the caudal TRN inhibition. The rostrally inhibited animals had a tendency for longer sleep and had a reduced proportion of the short sleep episodes relatively to the mice with caudally inhibited TRN. Lastly, we demonstrated that the caudal and rostral TRN are taking part in the brain state transition. The caudal part of the nucleus appears important for the wake - NREM sleep transition and the rostral TRN activation is associated with the sleep-wake transition. Although, it was a basic way to test the hypothesis, we concluded that rostral and caudal TRN consist of distinct subnetworks which have different activity levels during sleep. This is the first known description of TRN heterogeneity based on the location principles