UNASSIGNED: Despite an established link between @entity302 and @entity146 , it remains unclear how specific epileptogenic mutations affect sleep and subsequently influence @entity410 susceptibility. Recently, Sun et al. (2012) created a @entity238 knock-in model of @entity1 @entity31467 (GEFS+), a wide-spectrum disorder characterized by @entity221 in childhood and lifelong affliction. GEFS+ flies carry a disease-causing mutation in their voltage-gated @entity1372 channel (VGSC) gene and display semidominant heat-induced seizing, likely due to reduced GABAergic inhibitory activity at high temperature. Here, we show that at room temperature the GEFS+ mutation dominantly modifies sleep, with mutants exhibiting rapid sleep onset at dusk and increased nighttime sleep as compared to controls. These characteristics of GEFS+ sleep were observed regardless of sex, mating status, and genetic background. GEFS+ mutant sleep phenotypes were more resistant to pharmacologic reduction of @entity1246 transmission by @entity2049 ( @entity8358 ) than controls, and were mitigated by reducing GABAA receptor expression specifically in wake-promoting @entity14305 ( @entity14305 ) neurons. These findings are consistent with increased GABAergic transmission to @entity14305 neurons being mainly responsible for the enhanced nighttime sleep of GEFS+ mutants. Additionally, analyses under other light conditions suggested that the GEFS+ mutation led to reduced buffering of behavioral responses to light on and off stimuli, which contributed to characteristic GEFS+ sleep phenotypes. We further found that GEFS+ mutants had normal circadian rhythms in free-running dark conditions. Interestingly, the mutants lacked a homeostatic rebound following mechanical @entity1949 , and whereas deprivation treatment increased heat-induced @entity410 susceptibility in control flies, it unexpectedly reduced @entity410 activity in GEFS+ mutants. Our study has revealed the sleep architecture of a @entity238 VGSC mutant that harbors a @entity1 GEFS+ mutation, and provided unique insight into the relationship between sleep and @entity302 .

Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a XXXX Knock-In Model of @entity1 Epilepsy.

@entity1 :: ('9606', 'Species') :: ['human'] @entity31467 :: ('MESH:C565808', 'Disease') :: ['generalized epilepsy with febrile seizures plus'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizure'] @entity1949 :: ('MESH:D012892', 'Disease') :: ['sleep deprivation'] @entity1246 :: ('MESH:D005680', 'Chemical') :: ['GABA'] @entity146 :: ('MESH:D001523', 'Disease') :: ['sleep behavior'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity2049 :: ('MESH:D002220', 'Chemical') :: ['carbamazepine'] @entity8358 :: ('D002220', 'Chemical') :: ['CBZ'] @entity302 :: ('MESH:D004827', 'Disease') :: ['epilepsy'] @entity14305 :: ('64146', 'Gene') :: ['PDF', 'pigment dispersing factor'] @entity221 :: ('MESH:D005334', 'Disease') :: ['fever-associated seizing'] @entity238 :: ('7227', 'Species') :: ['fly', 'Drosophila']
@entity238 :: (7227,Species) :: ['Drosophila']
