The Involvement of CaBP1 in Hippocampus-Dependent Spatial Learning and Memory

Ca_v1 channels are L-type voltage-gated pathways that mediate the influx of Ca²⁺ into the cell upon membrane polarization. Ca_v1 channels, mostly Ca_v1.2 and Ca_v1.3, are widely expressed in the brain and are associated with a variety of psychiatric disorders, including depression and schizophrenia. Because of this, the modulation of these channels is of great research interest due to their potential uses as therapeutic targets. CaBP1 is a Ca²⁺ binding protein that is highly expressed in the retina, inner ear, and brain, and though its functions in the nervous system are still primarily unknown, it has been previously established that CaBP1 suppresses Ca²⁺-dependent inactivation (CDI) of Ca_v1 in heterologous expression systems. CaBP1 is thought to inhibit CDI to restrict excessive calcium influx of the cells, which could be pathological. To analyze if CaBP1 plays a role in psychiatric disorders by modulation of Ca_v1 channels, mice lacking expression of CaBP1 (C-KO) were used to investigate the role of CaBP1 as a regulator of voltage–gated Ca_v­1 L-type Ca²⁺ channels, spatial learning, and memory. Barnes maze and Morris water maze behavioral experiments were conducted showing that CaBP1 KO mice have mild learning defects compared to wild-type (WT) mice. In electrophysiological analyses, Ca_v currents underwent greater Ca²⁺-dependent inactivation in C-KO than in WT neurons form the hippocampus of mice. Our findings establish CaBP1 as a regulator for spatial learning and memory, possibly through inhibiting CDI of CaBP1.