0120 SUPRA-SPINAL NEURAL CIRCUITRY REGULATING REST LEGS SYNDROME (RLS)

• Published in: Sleep (New York, N.Y.) Vol. 40; no. suppl_1; p. A45
• Main Authors: Guo, C, Yang, W, Zhan, S, Yang, X, Chen, M, Fuller, P, Lu, J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 28.04.2017
• Subjects: Dopamine; Restless legs syndrome; Sleep; Spinal cord
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleepj/zsx050.119

Abstract Introduction: RLS occurs in sleep-wake transitions and during sleep as uncomfortable sensation causes leg movements (sometimes other parts of the body). We propose that corticospinal and rubrospinal tract, and hypothalamic A11 dopaminergic projection to the spinal cord are involved in RLS. Because basal ganglia strongly regulate the cerebral cortex including motor cortex, we hypothesize that the basal ganglia, via the cortex and corticospinal tract, is involved in regulation of RLS. Methods: To dissect the roles of three supra-pontine descending projections in RLS, we systemically made lesions of corticospinal tract and its sources (motor cortex and somatosensory cortex), red nucleus (RN) and its afferent cerebellar interposed nucleus (IP) and hypothalamic A11 dopaminergic descending projections and examined RLS like movements and sleep-wake structure following ablating these projections. Finally, we injected dopamine agonist pramipexole, a drug of choice for RLS, to examine if RLS like movements are reduced. To investigate the roles of the basal ganglia in RLS, we examined the effects of selective lesions in substantia nigra pars compacta (SNc), striatum, globus pallidus externa (GPe), and pallidocortical neurons on RLS-like movements. Results: Damaging corticospinal tract (CST), rubrospinal tract and A11 and their afferent sources (motor and somatosensory cortex and cerebellar interposed nucleus) induced abnormal (twitching and jerking) movements (RLS-like movements) during sleep and its transitions into quiet wakefulness (N->W and R->W). Overall, more number of RLS-like movements with more vigorous were seen during night than daytime. Dopamine D2 agonist pramipexole, a drug for RLS treatment, reduced RLS like movements significantly, which indirectly indicates that RLS-like movements resemble RLS. Finally, we revealed the neural pathways of the basal ganglia involved in control of RLS-like movements. In particular, we identified the pallidocortical neurons in GPe as a key node for basal ganglia control of motor cortex regulating RLS-like movements. Conclusion: Corticospinal, rubrospinal and A11 descending projections are engaged in regulation of motor activity during sleep and sleep transitions. Basal ganglia, via GPe-cortex-spinal cord pathway, regulate RLS. Support (If Any): NS061849 and NS09586.