CALCIUM-SENSING RECEPTOR IN THE RAT HIPPOCAMPUS - A DEVELOPMENTAL-STUDY

The extracellular Ca2+ (Ca-o(2+))-sensing receptor (CaR) plays a key r ole in maintaining near constancy of Ca-o(2+) in mammals through its p resence in parathyroid gland and kidney. The CaR is also present in br ain, and although its role(s) in the brain is not known, it is possibl e that small changes in Ca-o(2+) modify essential physiological and pa thological processes, since calcium is crucial for numerous neuronal f unctions. 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 th e CaR to these processes is unknown. Long-term potentiation (LTP), a p utative in vitro analog of memory, can only be induced after 7-10 days postnatally in rat hippocampus. Therefore, in the present study we de termined the time course for the developmental expression of the CaR i n rat hippocampus to assess its relationship to the development of oth er important hippocampal functions, such as the capacity for induction of LTP. Northern and Western analyses showed that CaR mRNA and protei n were expressed at low levels at 5 days postnatally but then increase d markedly at 10 days. A high level of receptor expression, due primar ily to an increase in a 7.5 kb transcript, persisted until 30 days, wh en it gradually decreased by 3-fold to reach the adult level of expres sion. In situ hybridization histochemistry and immunohistochemistry re vealed CaR mRNA and protein in pyramidal cells of all the layers of hi ppocampus 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 h ippocampus and persists at high levels during the time when brain deve lopment is proceeding most rapidly. Further studies are needed to dete rmine the role of the CaR in the development of important aspects of t he function of hippocampus and other regions of brain, including LTP. (C) Elsevier Science B.V.