Fast cerebellar oscillation associated with ataxia in a mouse model of Angelman syndrome.
Ataxia may result from various cerebellar cortex dysfunctions. It is included in the diagnostic criteria of Angelman syndrome, a human neurogenetic condition. In order to better understand the cerebellar dysfunction in this condition, we recorded in vivo cerebellar activity in a mouse model of Angelman syndrome produced by null mutation of the maternal Ube3a gene. We found fast oscillation (approximately 160 Hz) in the cerebellar cortex sustained by abnormally increased Purkinje cell firing rate and rhythmicity. This oscillation is inhibited by sensory stimulation and gap junction or GABA(A) receptor blockers. A physiologically similar oscillation was previously found in mice lacking calcium-binding proteins that also present ataxia, but never in wild-type mice. We propose that fast oscillation in the cerebellar cortex is implicated in the cerebellar symptomatology of Angelman syndrome.
Cheron
G
G
Laboratory of Electrophysiology, Université Mons-Hainaut, 7000 Mons, Belgium. gcheron@ulb.ac.be
Servais
L
L
Wagstaff
J
J
Dan
B
B
D017204:Angelman Syndrome / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000503:physiopathology*; D002229:Carbenoxolone / Q000494:pharmacology; D002531:Cerebellum / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D017629:Gap Junctions / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008845:Microinjections; D009154:Mutation / Q000502:physiology; D010812:Physical Stimulation; D011689:Purkinje Cells / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D009435:Synaptic Transmission; D014738:Vibrissae
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D020662:Guanine Nucleotide Exchange Factors; C486527:Herc2 protein, mouse; D011724:Pyridazines; C049853:gabazine; D002229:Carbenoxolone