The Department of Biomedicine

BBB Seminar: Pierre-Hervé Luppi

The neuronal network responsible for paradoxical (REM) sleep and its dysfunctions causing narcolepsy and REM behavior disorder

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Pierre-Hervé Luppi
Center of Neuroscience of Lyon, National Center for Scientific Research (CNRS), Claude Bernard University Lyon, France

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during paradoxical (REM) sleep (PS). Conversely, cataplexy, one of the key symptoms of narcolepsy, is a striking sudden episode of muscle weakness triggered by emotions during wakefulness, and comparable to REM sleep atonia. The neuronal dysfunctions responsible for RBD and cataplexy are not known. In my talk, I will present the most recent results on the neuronal network responsible for PS. Based on this, I will propose an updated integrated model of the mechanisms responsible for PS and explore different hypotheses explaining RBD and cataplexy.

I propose that RBD is due to a specific degeneration of a sub-population of PS-on glutamatergic neurons specifically responsible for muscle atonia, localized in the caudal pontine sublaterodorsal tegmental nucleus (SLD). Another possibility is the occurrence in RBD patients of a specific lesion of the glycinergic/GABAergic premotoneurons localized in the medullary ventral gigantocellular reticular nucleus. Conversely, cataplexy in narcoleptics would be due to the activation during waking of the caudal PS-on SLD neurons responsible for muscle atonia. A phasic glutamatergic excitatory pathway from the central amygdala to the SLD PS-on neurons activated during emotion would induce such activation. In normal conditions, the glutamate excitation would be blocked by the simultaneous excitation by the hypocretins of the PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray and the adjacent deep mesencephalic reticular nucleus, gating the activation of the PS-on SLD neurons.

Host: Jonathan Soule, Department of Biomedicine