Limna - Lausanne Integrative Metabolism Nutrition Alliance


Monday 25th January 2016
12h15 Department of Physiology, Bugnon 7, 1005 Lausanne - seminar room, 6th floor

Deletion of astrocytic connexin 43 causes narcolepsy‐like phenotype

Dr. Jérôme Clasadonte

Haydon Lab, Tufts University, Neuroscience Department, Boston, USA

Host: Prof. Luc Pellerin

The involvement of the glial  cells,  astrocytes,  in  information  processing  in  the  brain  has  mainly been studied at the level of the single astrocyte, often missing the role of astrocyte networks in this process. Here, we investigated the role of the astrocytic gap-­‐junction subunit proteins connexin (Cx) 43 in brain circuit in vivo. Usingastrocyte-­‐specific Cre recombinase in mice (Cx43 KO mice), we have deleted the Cx43 gene in astrocytes and evaluated the consequences of disruption  of astrocytenetworks on behavior. Electroencephalographic (EEG) recordings in Cx43 KO mice indicated excessive sleepiness and fragmented wakefulness during the subjective  daytime  (dark phase), suggesting a narcolepsy‐like phenotype in these animals. Given the importance of orexin neurons from the lateral hypothalamus in narcolepsy, we asked whether their activity was affected. Patch-­‐clamp recordings of these cells in brain slices from Cx43 KO mice indicated a reduced spontaneous activity. Because Cx43 dysfunction has been linked with altered astrocyte-­‐to-­‐neuron lactate shuttling, we asked whether a reduced supply of lactate might contribute to  this  phenotype.  In support of this hypothesis, chronic delivery of lactate into the lateral hypothalamus of Cx43 KO mice restored both tonic firing of orexin neurons and daily cycle of wakefulness. Altogether, these data raise the exciting possibility that an astrocytic source of lactate is critical for the normal activity patterns of orexin neurons and, as a consequence, for normal daily cycles of wakefulness.