Illuminating the functions of CACNA2D4 in the brain

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Project Summary Variants in the genes that encode voltage-gated Ca2+ channels are consistently and robustly associated with schizophrenia, bipolar disorder, and autism spectrum disorder. One of these genes is CACNA2D4, an IDG-elibigle gene that encodes an extracellular Ca2+ channel subunit (2-4) expressed in both the brain and retina. In the case of the retina, it has been established that 2-4 is required for normal vision. By contrast, the role of this protein in the brain remains understudied; we known neither where in the brain it acts nor what functions it may have there. The long-term goal of this project is to understand how genetic alterations in Cav-channel contributes to the complex etiology of neuropsychiatric disorders. The overall objective of the proposed research is to establish the cellular distribution of 2-4 in the mouse brain and which behaviors are disrupted in mice lacking this protein. The specific aims are to (1) define the neural circuits that may be regulated by 2–4 in the mouse brain and (2) identify cognitive/affective phenotypes in 2-4 knock-out mice. To accomplish these aims, we will use antibodies against 2–4 in immunohistochemical analyses of mouse brain, and behavioral analyses designed to uncover alterations in cognitive or affective function in mice.