PT  - JOURNAL ARTICLE
AU  - Jivan Khlghatyan
AU  - Alesya Evstratova
AU  - Lusine Bozoyan
AU  - Simon Chamberland
AU  - Aleksandra Marakhovskaia
AU  - Tiago Soares Silva
AU  - Katalin Toth
AU  - Valerie Mongrain
AU  - Jean-Martin Beaulieu
TI  - Fxr1 regulates sleep and synaptic homeostasis
AID  - 10.1101/709345
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 709345
4099  - http://biorxiv.org/content/early/2019/10/30/709345.short
4100  - http://biorxiv.org/content/early/2019/10/30/709345.full
AB  - The fragile X autosomal homolog 1 (Fxr1) has been GWAS-associated to schizophrenia and insomnia but its contributions to brain functions are unclear. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and engages both global and cell autonomous level processes. We used Crispr/Cas9-mediated somatic knockouts, overexpression, neuronal activity recordings and translatome sequencing, to examine the contribution of Fxr1 to cell-autonomous homeostatic synaptic scaling and global-level sleep homeostasis. Our findings indicate that Fxr1 is downregulated during scaling and sleep deprivation via a Gsk3β dependent mechanism. In both conditions, downregulation of Fxr1 is essential for the homeostatic modulation of synaptic strength. Furthermore, overexpression of Fxr1 during sleep deprivation results in altered EEG signatures and reverts changes of translatome profiles. These findings indicate that Fxr1 represents a shared signaling hub linking cell autonomous homeostatic plasticity and system level sleep homeostasis with potential implications for neuropsychiatric illnesses.