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.
|Date of Award||10 Jun 2019|
- University Of Strathclyde
|Sponsors||EPSRC (Engineering and Physical Sciences Research Council), University of Strathclyde & BBSRC (Biotech & Biological Sciences Research Council)|
|Supervisor||Judith Pratt (Supervisor) & Shuzo Sakata (Supervisor)|