Ablation of Ca2+ channel beta 3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory

Abstract

The beta subunits of voltage-dependent Ca2+ 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 beta 3) is abundantly expressed in the hippocampus. However, the role of Ca-v beta 3 in hippocampal physiology and function in vivo has never been examined. Here, we investigated Ca-v beta 3-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 Ca2+ 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 beta 3 negatively regulates the NMDAR activity in the hippocampus and thus activity-dependent synaptic plasticity and cognitive behaviors in the mouse.