The neuronal Ca2+ signal is induced by a rise in the intracellular free Ca2+ concentration ([Ca2+]i), and is thought to be important for higher brain function. Dynamic changes in [Ca2+]i are affected by the spatial distributions of various Ca(2+)-increasing molecules (channels and receptors). The ryanodine receptor (RyR) is an intracellular channel through which Ca2+ is released from intracellular stores. To define the contribution of neuronal Ca2+ signaling via the RyR channel, we examined RyR type-specific gene expression in rabbit brain by in situ hybridization histochemistry. The neuronal RyR was composed of three distinct types, two types dominant in skeletal (sRyR) and cardiac (cRyR) muscle, respectively, and a novel brain type (bRyR). sRyR was distinguished by its high level of expression in cerebellar Purkinje cells. cRyR was predominantly expressed throughout nearly the entire brain, and was characterized by its markedly high level of expression in the olfactory nerve layer, layer VI of the cerebral cortex, the dentate gyrus, cerebellar granule cells, the motor trigeminal nucleus, and the facial nucleus. bRyR expression was the least widely distributed throughout the brain, and was high in the hippocampal CA1 pyramidal layer, caudate, putamen, and dorsal thalamus. This investigation demonstrates that the heterogeneous distribution of neuronal RyRs may be implicated in distinct Ca(2+)-associated brain functions. Moreover, it should be noted that cRyR, a typical CICR channel, is distributed widely throughout the brain, suggesting that in a variety of cell types, the amplification of neuronal Ca2+ signals is functionally accompanied by a rise in [Ca2+]i, such as Ca2+ influx stimulated by neuronal activity. This widespread distribution of the neuronal RyR family indicates that Ca2+ signals via the intracellular stores should be considered in studies of neuronal Ca2+ dynamics.