A.Taxia affects individuals’ ability to walk, speak, and perform other motor functions. Genetic mutations that disrupt or destroy Purkinje cellsInhibitory neurons in the cerebellum, which coordinate movement and contribute to cognition and emotional processing, may cause this disorder.¹ But one group has provided further evidence that this brain structure may be involved in another non-motor function (sleep).

Reports sleep disorders aroused interest in people with ataxia Roy SillitoeHe’s a neuroscientist at Baylor College of Medicine.² When Luis SalazarWhen he joined Sillitoe’s group as a graduate student, who had previously done research on sleep, the perfect opportunity to investigate this interaction arose. “It seemed like a really fertile area to study and explore, and it hadn’t been studied in laboratory mouse models,” said Salazar, who now co-founded Sobek AI.

In an article published in Disease Models and Mechanisms, Salazar and colleagues showed that Purkinje cells affected by ataxia also control some aspects of the sleep cycle in mice.³ The findings contribute to the understanding of sleep disorders in people with motor disorders such as ataxia, which affect their overall health and quality of life. “We can start thinking about how we can treat this with medications or neurostimulation,” he said. Amanda Brownneuroscientist and postdoctoral researcher in Sillitoe’s laboratory and co-author of the paper.

Previously, the group investigated two models. dystoniashowed that preventing brainstem neurons from communicating with the cerebellum, a different motor disorder, disrupts sleep.⁴ “The idea from there was to look at another mouse model first,” Salazar said. “We’re also trying to unravel some of the cellular mechanisms that are at play here.”

Team selectively silenced to model ataxia Purkinje cells It caused ataxia-like motor disorders in mice.⁵ “We’re probably using one of the cleanest models of ataxia currently known in mice,” Brown said.

Because sleep is partially controlled by the circadian rhythm, the team first investigated changes in this internal clock in ataxic mice. They recorded how often the animals used the spinning wheel to establish activity patterns, and after an acclimation period to a 12-hour light-dark cycle, they assessed changes in these patterns by housing the mice in constant darkness. While silencing Purkinje cells reduced overall activity in ataxic mice, this manipulation did not affect the animals’ circadian rhythms.

The team then examined changes in the animals’ sleep cycles by examining electrical activity in the brain and muscles using electrodes. A normal sleep cycle in mice includes Three stages the animal alternates between: wakefulness, rapid eye movement (REM), and non-REM (NREM).⁶

Ataxic mice experienced longer periods in each phase, although they had fewer periods of wakefulness and REM; thus, overall, these mice spent more time in NREM sleep compared to wakefulness or REM phases. These mice also took longer to enter REM sleep. Specifically, these REM sleep deficits REM sleep disorders It occurs in people with ataxia.⁷

“This provides a good scientific basis for further research,” he said Sheng-Han KuoA neurologist and translational neuroscientist at Columbia University who was not involved in this study. Because motor impairments can cause other confounding effects, investigating the role of Purkinje cells with specific approaches such as optogenetics could help further support their involvement in sleep regulation, he said. Sillitoe’s group also wants to study the effects in more complex disease models that more closely resemble human diseases.

“Some very interesting next steps would be to look at these abnormal downstream signals and see how they affect sleep processes and other non-motor functions, particularly in these neurological disorders,” Brown said.