Involvement of hippocampal CA3 K(ATP) channels in contextual memory.
This paper evaluates the involvement of hippocampal ATP-sensitive potassium channels (K(ATP)) in learning and memory. After confirming expression of the Kir6.2 subunit in the CA3 region of C57BL/6J mice, we performed intra-hippocampal pharmacological injections of specific openers and blockers of K(ATP) channels. The opener diazoxide, the blocker tolbutamide, or a mixture of both, were bilaterally injected in the CA3 region before we subjected the animals to a fear conditioning paradigm. Diazoxide strongly impaired contextual memory of mice at both doses tested. This impairment was specifically reversed by co-injecting the blocker tolbutamide. Moreover, we studied the mnemonic abilities of mice deleted for the Kir6.2 subunit. These mice were backcrossed to C57BL/6J mice and tested in two learning paradigms. We found a significant impairment of contextual and tone memories in the Kir6.2 knock-out mice when compared with heterozygous or wild-type animals. Furthermore, these animals were also slightly impaired in a spatial version of the Morris water maze task. Our data suggest a specific involvement of hippocampal K(ATP) Kir6.2/SUR1 channels in memory processes.
Betourne
Alexandre
A
Université de Toulouse, Centre de Recherches sur la Cognition Animale, France.
Bertholet
Ambre M
AM
Labroue
Elodie
E
Halley
Hélène
H
Sun
Hong Shuo
HS
Lorsignol
Anne
A
Feng
Zhong-Ping
ZP
French
Robert J
RJ
Penicaud
Luc
L
Lassalle
Jean-Michel
JM
Frances
Bernard
B
D000818:Animals; D003981:Diazoxide / Q000494:pharmacology; D005239:Fear; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D054086:KATP Channels / Q000819:agonists* / Q000037:antagonists & inhibitors*; D008124:Locomotion; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D014044:Tolbutamide / Q000494:pharmacology; D000099161:Kcnj11 Channel
D003981:Diazoxide; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D014044:Tolbutamide; D000099161:Kcnj11 Channel