Pierre-Hervé Luppi, PhD, University of Lyon, Lyon, France, discusses the work being done to identify the mechanisms responsible for generating muscle atonia during paradoxical (REM) sleep. Multimodal investigations have been critical to elucidating the role of various systems and neuronal populations in REM sleep. Structural connectivity techniques, neurochemical anatomy, imaging, and optogenetic and electrophysiological recordings have all been conducted. Anterograde and retrograde tracing were combined with cFos immunostaining as a marker of neuronal activation, which identified multiple populations of neurons indicated in REM sleep generation. The next stages were to use transgenic mice to observe the effects of activation/inactivation of these neurons. Identifying the precise neuronal networks activated is an ongoing challenge where more research is needed. This interview took place during the European Academy of Neurology 2021 congress.