Treated mice slept more normally, expressed twice as much FosB/ΔFosB, and had 40 percent fewer plaques (see image below). To test if long-term TRN activation could reduce plaque load, Jagirdar injected 6-month-old mice with either CNO or saline before they fell asleep they did this every day for a month and recorded EEG/EMG sleep data every five days. After injection of a virus encoding a CNO-inducible receptor labeled with mCherry dye ( red ), TRN tissue from mice given CNO (right) have more cells expressing FosB/Δ FosB (green) than mice given saline (left). Mice manipulated in this way awoke less often, got more SWS, and had restored TRN neuron activity compared to animals given saline (see image below).Ī DREADDed TRN.
To activate the receptor and jolt the TRN, the researchers fed the mice clozapine N-oxide (CNO Roth, 2017). In short, they injected a virus carrying a synthetic excitatory receptor into the TRN of 2-month-old mice, then implanted electrodes to measure EEG/EMG. By 6 months, the mice awoke even more often, as amyloid plaques also developed.Ĭould making the TRN more active correct abnormal sleep? To address this question, the scientists used the “designer receptor exclusively activated by designer drug” (DREADD) method. Synchronous firing of neurons during SWS helps convert short- to long-term memories and drain waste products from the brain ( Jun 2015 news Nov 2019 news). This was done with J20s only.Ĭompared to controls, 2-month-old J20 mice woke up twice as often, slept an hour less, and spent less time in slow-wave sleep. They implanted electrodes into the mice's frontal lobes and neck muscles to record electroencephalographs and electromyographs, respectively, as they slept.
To see if the inactive TRN neurons affect sleep, the scientists video-monitored the mice's sleep and wake times in their cages. This suggested that impaired TRN activity may be a shared feature among AD and amyloidosis. Similarly, the researchers detected less FosB/ΔFosB in TRN tissue from J20 mice and two other sleep-disturbed models of amyloidosis, APP/PS1 and Tg2576, compared to controls. TRN tissue from people with AD (red) or MCI (blue) expressed less of the neuronal activity marker FosB/ΔFosB than controls (gray). This marker tracked with Braak stage (see image below). Compared to controls, neurons in diseased tissue expressed less FosB/∆FosB, a marker thought to reflect a history of neuronal activity. “The TRN plays a critical role in coordinating network oscillations during sleep that are thought to be important for its beneficial effects on memory,” Lewis wrote.ĭid activity dwindle in this region in people too? First author Rohan Jagirdar immunostained TRN tissue from 10 people who had had AD, three people who had had mild cognitive impairment, and 15 age-matched controls from the NIH NeuroBioBank. The TRN consists of a thin sheet of mostly inhibitory GABA-ergic neurons that surround the thalamus and block sensory input to enable undisturbed snoozing ( Steriade and Timofeev, 2003 Fogerson and Huguenard, 2016 Lewis et al., 2015).
Previously, Chin and colleagues noticed that J20 mice slept intermittently, and that their thalamic reticular nuclei were less active than those of control mice ( Hazra et al., 2016). “This work suggests a causal role of the TRN in mediating sleep and AD risk,” he wrote (full comment below). Luigi de Gennaro, University of Rome, Italy, agreed. “This study is exciting because it directly shows that manipulating a specific sleep-related brain circuit can restore sleep and reduce Aβ plaques,” Laura Lewis of Boston University wrote to Alzforum.