Ablation of Ca2+ channel beta3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory.
The beta subunits of voltage-dependent Ca(2+) channels (VDCCs) have marked effects on the properties of the pore-forming alpha(1) subunits of VDCCs, including surface expression of channel complexes and modification of voltage-dependent kinetics. Among the four different beta subunits, the beta(3) subunit (Ca(v)beta3) is abundantly expressed in the hippocampus. However, the role of Ca(v)beta3 in hippocampal physiology and function in vivo has never been examined. Here, we investigated Ca(v)beta3-deficient mice for hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses. Interestingly, the mutant mice exhibited enhanced performance in several hippocampus-dependent learning and memory tasks. However, electrophysiological studies revealed no alteration in the Ca(2+) current density, the frequency and amplitude of miniature excitatory postsynaptic currents, and the basal synaptic transmission in the mutant hippocampus. On the other hand, however, N-methyl-d-aspartate receptor (NMDAR)-mediated synaptic currents and NMDAR-dependent long term potentiation were significantly increased in the mutant. Protein blot analysis showed a slight increase in the level of NMDAR-2B in the mutant hippocampus. Our results suggest a possibility that, unrelated to VDCCs regulation, Ca(v)beta3 negatively regulates the NMDAR activity in the hippocampus and thus activity-dependent synaptic plasticity and cognitive behaviors in the mouse.
Jeon
Daejong
D
Center for Neural Science, Korea Institute of Science and Technology, Seoul 136-791, Korea.
Song
Inseon
I
Guido
William
W
Kim
Karam
K
Kim
Eunjoon
E
Oh
Uhtaek
U
Shin
Hee-Sup
HS
D000818:Animals; D020746:Calcium Channels, L-Type / Q000172:deficiency* / Q000378:metabolism; D005239:Fear; D005518:Food Preferences; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism; D015640:Ion Channel Gating; D017774:Long-Term Potentiation / Q000502:physiology*; D008564:Membrane Potentials; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000172:deficiency*; D017966:Pyramidal Cells / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D021641:Recognition, Psychology; D009435:Synaptic Transmission
D020746:Calcium Channels, L-Type; C121001:NR2B NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate