Ca2+-Binding Protein 1 Regulates Hippocampal-dependent Memory and Synaptic Plasticity

Neuroscience. 2018 Jun 1;380:90-102. doi: 10.1016/j.neuroscience.2018.04.004. Epub 2018 Apr 14.

Abstract

Ca2+-binding protein 1 (CaBP1) is a Ca2+-sensing protein similar to calmodulin that potently regulates voltage-gated Ca2+ channels. Unlike calmodulin, however, CaBP1 is mainly expressed in neuronal cell-types and enriched in the hippocampus, where its function is unknown. Here, we investigated the role of CaBP1 in hippocampal-dependent behaviors using mice lacking expression of CaBP1 (C-KO). By western blot, the largest CaBP1 splice variant, caldendrin, was detected in hippocampal lysates from wild-type (WT) but not C-KO mice. Compared to WT mice, C-KO mice exhibited mild deficits in spatial learning and memory in both the Barnes maze and in Morris water maze reversal learning. In contextual but not cued fear-conditioning assays, C-KO mice showed greater freezing responses than WT mice. In addition, the number of adult-born neurons in the hippocampus of C-KO mice was ∼40% of that in WT mice, as measured by bromodeoxyuridine labeling. Moreover, hippocampal long-term potentiation was significantly reduced in C-KO mice. We conclude that CaBP1 is required for cellular mechanisms underlying optimal encoding of hippocampal-dependent spatial and fear-related memories.

Keywords: Ca(2+); calmodulin; fear learning; hippocampus; memory; synaptic plasticity.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism*
  • Hippocampus / physiology*
  • Long-Term Potentiation / physiology*
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Spatial Learning / physiology*

Substances

  • Calcium-Binding Proteins
  • Ca2+-binding protein-1