Gamma-band deficiency and abnormal thalamocortical activity in P/Q-type channel mutant mice.
Thalamocortical in vivo and in vitro function was studied in mice lacking P/Q-type calcium channels (Cav2.1), in which N-type calcium channels (Cav2.2) supported central synaptic transmission. Unexpectedly, in vitro patch recordings from thalamic neurons demonstrated no gamma-band subthreshold oscillation, and voltage-sensitive dye imaging demonstrated an absence of cortical gamma-band-dependent columnar activation involving cortical inhibitory interneuron activity. In vivo electroencephalogram recordings showed persistent absence status and a dramatic reduction of gamma-band activity. Pharmacological block of T-type calcium channels (Cav3), although not noticeably affecting normal control animals, left the knockout mice in a coma-like state. Hence, although N-type calcium channels can rescue P/Q-dependent synaptic transmission, P/Q calcium channels are essential in the generation of gamma-band activity and resultant cognitive function.
Llinás
Rodolfo R
RR
Department of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. llinar01@med.nyu.edu
Choi
Soonwook
S
Urbano
Francisco J
FJ
Shin
Hee-Sup
HS
D000818:Animals; D020864:Calcium Channels, N-Type / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D003071:Cognition / Q000502:physiology; D004569:Electroencephalography; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018408:Patch-Clamp Techniques; D009435:Synaptic Transmission / Q000502:physiology*; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology
D020864:Calcium Channels, N-Type; C500963:Cacna1b protein, mouse