Impaired long-term memory and long-term potentiation in N-type Ca2+ channel-deficient mice.
Voltage-dependent N-type Ca(2+) channels, along with the P/Q-type, have a crucial role in controlling the release of neurotransmitters or neuromodulators at presynaptic terminals. However, their role in hippocampus-dependent learning and memory has never been examined. Here, we investigated hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses in mice deficient for the alpha(1B) subunit of N-type Ca(2+) channels. The mutant mice exhibited impaired learning and memory in the Morris water maze and the social transmission of food preference tasks. In particular, long-term memory was impaired in the mutant mice. Interestingly, among activity-dependent long-lasting synaptic changes, theta burst- or 200-Hz-stimulation-induced long-term potentiation (LTP) was decreased in the mutant, compared with the wild-type mice. This type of LTP is known to require brain-derived neurotrophic factor (BDNF). It was found that both BDNF-induced potentiation of field excitatory postsynaptic potentials and facilitation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) were reduced in the mutant. Taken together, these results demonstrate that N-type Ca(2+) channels are required for hippocampus-dependent learning and memory, and certain forms of LTP.
Jeon
D
D
Center for Neural Science, Korea Institute of Science and Technology, Seoul, Republic of Korea.
Kim
C
C
Yang
Y-M
YM
Rhim
H
H
Yim
E
E
Oh
U
U
Shin
H-S
HS
D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D005518:Food Preferences / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016037:Single-Blind Method; D012919:Social Behavior; D013037:Spatial Behavior / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; C500963:Cacna1b protein, mouse; D020864:Calcium Channels, N-Type