Calcium-sensing receptor in the rat hippocampus: a developmental study

The extracellular Ca2+ (Ca2+(o))-sensing receptor (CaR) plays a key role in maintaining near constancy of Ca2+(o) in mammals through its presence in parathyroid gland and kidney. The CaR is also present in brain, and although its role(s) in the brain is not known, it is possible that small changes in Ca2+(o) modify essential physiological and pathological processes, since calcium is crucial for numerous neuronal functions. Northern analysis has revealed that the CaR mRNA is present in hippocampus and several other regions of the brain. The hippocampus is an important site for learning and memory, but the relevance of the CaR to these processes is unknown. Long-term potentiation (LTP), a putative in vitro analog of memory, can only be induced after 7-10 days postnatally in rat hippocampus. Therefore, in the present study we determined the time course for the developmental expression of the CaR in rat hippocampus to assess its relationship to the development of other important hippocampal functions, such as the capacity for induction of LTP. Northern and Western analyses showed that CaR mRNA and protein were expressed at low levels at 5 days postnatally but then increased markedly at 10 days. A high level of receptor expression, due primarily to an increase in a 7.5 kb transcript, persisted until 30 days, when it gradually decreased by 3-fold to reach the adult level of expression. In situ hybridization histochemistry and immunohistochemistry revealed CaR mRNA and protein in pyramidal cells of all the layers of hippocampus and in granule cells of the dentate gyrus. The results show that CaR expression rises at a time when LTP can first be induced in hippocampus and persists at high levels during the time when brain development is proceeding most rapidly. Further studies are needed to determine the role of the CaR in the development of important aspects of the function of hippocampus and other regions of brain, including LTP.