C\u2019est \u00e0 Lyon \u00e0 la fin des ann\u00e9es 1950 que le Professeur M. Jouvet, d\u00e9c\u00e9d\u00e9 en octobre 2017, a d\u00e9couvert une phase particuli\u00e8re du sommeil physiologique des mammif\u00e8res caract\u00e9ris\u00e9e par une activit\u00e9 corticale tr\u00e8s similaire \u00e0 celle de l\u2019\u00e9veil paradoxalement associ\u00e9e \u00e0 une immobilit\u00e9 corporelle r\u00e9sultant d\u2019une atonie de la musculature posturale. Ce sommeil dit \u00ab\u00a0paradoxal\u00a0\u00bb (SP) s\u2019av\u00e8re \u00eatre le si\u00e8ge privil\u00e9gier de l\u2019activit\u00e9 onirique et mais aussi de processus complexes sous-jacents de l\u2019apprentissage, la m\u00e9moire et l\u2019humeur. Apr\u00e8s plusieurs d\u00e9cennies de d\u00e9bats au sein de la communaut\u00e9 scientifique internationale, notre \u00e9quipe du Centre de Recherche en Neurosciences de Lyon (CRNL) vient de compl\u00e9ter le d\u00e9cryptage des circuits neuronaux responsables de cette paralysie propre au SP, ouvrant de fait des champs d\u2019investigation pour comprendre le SP physiologique et ses pathologies.<\/p>\n
Apr\u00e8s avoir d\u00e9crit les neurones glutamate du tegmentum pontique g\u00e9n\u00e9rateurs du ph\u00e9nom\u00e8ne (Valencia Garcia et coll., Brain 2017), nous avons cette fois-ci identifi\u00e9 l\u2019ultime maillon du r\u00e9seau neuronal mis en jeu pendant le SP. Par une combinaison de techniques neuroanatomiques chez le rat, nous avons d\u2019abord d\u00e9montr\u00e9 que les neurones inhibiteurs actifs pendant le SP et aff\u00e9rents aux motoneurones somatiques (cr\u00e2niens et spinaux) sont exclusivement localis\u00e9s dans la formation r\u00e9ticul\u00e9e ventrom\u00e9diane (vmM) du bulbe rachidien, et non comme g\u00e9n\u00e9ralement admis jusqu\u2019\u00e0 maintenant dans la moelle \u00e9pini\u00e8re. Pour caract\u00e9riser leur implication fonctionnelle suppos\u00e9e dans l\u2019expression du SP, nous avons obtenu leur inactivation g\u00e9n\u00e9tique (knockout) par l\u2019infusion locale de vecteurs viraux (AAVs) v\u00e9hiculant un short-hairpin ARN dirig\u00e9 contre les ARNs du transporteur v\u00e9siculaire du GABA\/glycine (vGAT-shRNA), bloquant ainsi d\u00e9finitivement et en quelques jours seulement la production de ce transporteur dans les neurones GABA\/glycine vis\u00e9s. Bien qu\u2019encore fonctionnels dans le vmM, ces neurones deviennent incapables de s\u00e9cr\u00e9ter leurs neurotransmetteurs dans l\u2019espace synaptique et donc d\u2019inhiber leurs cibles post-synaptiques (i.e. les motoneurones), comme d\u00e9connect\u00e9s des r\u00e9seaux neuronaux auxquels ils appartiennent. Bien que profond\u00e9ment endormis, les paupi\u00e8res ferm\u00e9es et isol\u00e9s de l\u2019environnement, les rats ainsi trait\u00e9s dans la vmM ne sont plus paralys\u00e9s pendant le SP (perte d\u00e9finitive de l\u2019atonie musculaire) et ex\u00e9cutent des mouvements anormaux brusques, violents, incontr\u00f4l\u00e9s, parfois coordonn\u00e9s (reptation, prise alimentaire, etc), refl\u00e9tant probablement l\u2019expression de leurs r\u00eaves.<\/p>\n
Ces donn\u00e9es exp\u00e9rimentales chez le rat soutiennent le r\u00f4le pr\u00e9pond\u00e9rant des neurones inhibiteurs de la vmM dans l\u2019expression physiologique de l\u2019atonie musculaire du SP. Par ailleurs, elles r\u00e9capitulent finement le tableau symptomatique rapport\u00e9 pendant le SP chez des patients souffrants de REM sleep Behavior Disorder (RBD), une parasomnie se manifestant d\u00e8s la cinquantaine. Initialement consid\u00e9r\u00e9 comme idiopathique, des \u00e9tudes longitudinales r\u00e9centes ont \u00e9tabli que le RBD est en fait sous-jacent d\u2019une attaque synucl\u00e9inopathique au sein du tronc c\u00e9r\u00e9bral et qu\u2019il est un excellent marqueur prodromique \u00e0 dix ans d\u2019autres synucl\u00e9inopathies, principalement la maladie de Parkinson. Ce mod\u00e8le pr\u00e9clinique de RBD valid\u00e9 par notre \u00e9tude constitue une base exp\u00e9rimentale pour aborder maintenant les m\u00e9canismes physio-pathologiques d\u00e9pendants de l\u2019a-synucl\u00e9ine, ciblant le r\u00e9seau de l\u2019atonie musculaire propre au SP et potentiellement recrut\u00e9s lors de la conversion du RBD en maladie de Parkinson. Enfin, ce mod\u00e8le, acc\u00e9dant directement \u00e0 l\u2019expression de l\u2019activit\u00e9 onirique des rats pendant leur sommeil, permettra d\u2019aborder la question passionnante de l\u2019origine centrale des r\u00eaves et d\u2019\u00e9claircir les fonctions physiologique, cognitive et\/ou psychologique du SP.<\/p>\n
<\/p>\n
R\u00e9f\u00e9rence<\/p>\n
Valencia Garcia\u00a0S, Brischoux F, Cl\u00e9ment O, Libourel PA, Arthaud S, Lazarus M, Luppi PH, Fort P. Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep Behavior Disorder. Nature Communications. 2018 Feb 5; 9(1):504. doi: 10.1038\/s41467-017-02761-0. PMID: 29402935<\/p>\n
<\/p>\n
Contact chercheur: Dr Patrice Fort<\/p>\n
Equipe SLEEP – \u00a0Centre de Recherche\u00a0en Neurosciences de Lyon (CRNL)<\/p>\n
CNRS UMR5292 – Universit\u00e9 Claude Bernard Lyon1 – INSERM U1028<\/p>\n
7-11 rue Guillaume\u00a0Paradin<\/p>\n
69372 Lyon, cedex 08, France<\/p>\n
patrice.fort@univ-lyon1.fr<\/p>\n
+ (33) 4 78 77 10 41 –\u00a0Fax\u00a0: + (33) 4 78 77 10 22<\/p>\n
<\/p>\n
In the late 1950s, Professor M. Jouvet, who passed away in October 2017, discovered a particular phase of the mammalian sleep characterized by a cortical activity similar to that of awakening, paradoxically associated with body immobility due to a generalized muscle atonia of postural musculature. This so-called “Paradoxical Sleep” (PS) is concomitant to dreaming activity and other complex neurobiological processes underlying learning, memory and mood regulation. After several decades of debates, our team from the Lyon Neuroscience Research Center (CRNL) just completed the decoding of neuronal circuits responsible for the PS-specific paralysis, opening up new research fields to understand PS regulation and its pathologies.<\/p>\n
After the recent description of the brainstem glutamate neurons generating the phenomenon (Valencia Garcia et al., Brain 2017), we here identified the ultimate inhibitory link recruited during PS. By a combination of neuroanatomical techniques in the rat, we first demonstrated that inhibitory neurons activated during PS and sending monosynaptic inputs to the somatic (cranial and spinal) motoneurons are located in the ventromedial part of the medullary reticular formation (vmM), and not within the spinal cord as generally assumed. To characterize their functional involvement in PS expression, we performed their genetic inactivation (knockout) by local infusion of viral vectors (AAVs) carrying short-hairpin mRNAs complementary to mRNAs encoding for the GABA\/glycine vesicular transporter (vGAT), thus rapidly blocking the production of this protein in targeted medullary neurons. Still present and functional, the vmM GABA\/glycine neurons became unable to release their neurotransmitters and therefore to inhibit their postsynaptic targets (i.e. motoneurons), as they were disconnected from the neuronal networks to which they belong. Although deeply asleep, with closed eyelids and isolated from environment, rats treated with vGAT-shRNA in vmM were no longer paralyzed (permanent loss of muscle atonia) during PS and executed abnormal, violent and uncontrolled movements, likely revealing some dream enactments.<\/p>\n
These experimental data in rats support clearly the preponderant role of vmM inhibitory neurons in the physiological expression of muscle atonia during PS. In addition, they closely recapitulate the motor symptoms reported during PS in patients suffering REM sleep Behavior Disorder (RBD), a parasomnia that may occur at the age of 50. Firstly considered as an idiopathic pathology, recent longitudinal studies established that RBD is actually due to the development of a brainstem synucleinopathy and is considered to date as the best prodromal marker (\u00bb 10 years) of other synucleinopathies, as Parkinson\u2019s disease. In that context, this preclinical RBD model may represent a basis for further experiments aimed at deciphering the physio-pathological mechanisms which are dependent of \u03b1-synuclein and which evolve over years within the brainstem for the RBD conversion to Parkinson’s disease. This model will also be of particular interest for addressing intriguing questions regarding the origin of dreams and the physiological, cognitive or psychological functions of PS.<\/p>\n","protected":false},"excerpt":{"rendered":"
C\u2019est \u00e0 Lyon \u00e0 la fin des ann\u00e9es 1950 que le Professeur M. Jouvet, d\u00e9c\u00e9d\u00e9 en octobre 2017, a d\u00e9couvert une phase particuli\u00e8re du sommeil physiologique des mammif\u00e8res caract\u00e9ris\u00e9e par une activit\u00e9 corticale tr\u00e8s similaire \u00e0 celle de l\u2019\u00e9veil paradoxalement associ\u00e9e \u00e0 une immobilit\u00e9 corporelle r\u00e9sultant d\u2019une atonie de la musculature posturale. Ce sommeil dit […]<\/p>\n","protected":false},"author":4,"featured_media":9162,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[31],"class_list":["post-9142","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-actualite-en"],"publishpress_future_action":{"enabled":false,"date":"2026-04-24 14:21:38","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/9142","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/comments?post=9142"}],"version-history":[{"count":1,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/9142\/revisions"}],"predecessor-version":[{"id":9143,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/9142\/revisions\/9143"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media\/9162"}],"wp:attachment":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media?parent=9142"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/categories?post=9142"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/tags?post=9142"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}