Distribution of N-methyl d-aspartate (NMDA) receptor mRNAs in the rat suprachiasmatic nucleus

Abstract

Photic entrainment of the circadian oscillator located in the hypothalamic suprachiasmatic nucleus (SCN) is considered to be mediated at least partly by release of glutamate from the retinal presynaptic nerve terminals acting via a NMDA receptor. Several NMDA receptor subtypes have been cloned and expressed in model systems. The NMDA-R1 subtype is essential for the function of the NMDA receptor, and the multiple NMDA-R2(-A, -B, or -C) sububits potentiate and differentiate the function of the NMDA receptor by forming different heteromeric configuration with NMDA-R1. The aim of this study was to use in situ hybridization histochemistry with oligonucleotide sequences (42–48-mer) labeled with 35S to detect whether NMDA receptor mRNA is present in the rat SCN, and if so, to characterize which receptor subtypes occur. In order to identify the precise location of NMDA receptor mRNAs within the SCN, sections were dipped in emulsion and cellular resolution was achieved. The hybridization revealed a high abundance of NMDA-R1 mRNA in the SCN as well as in many other forebrain areas. The NMDA-R1 expressing cells were distributed throughout the SCN. NMDA-R2A and NMDA-R2B mRNAs were found in the hippocampus, but not in the SCN. In contrast, NMDA-R2C mRNA was found in relative high amounts in the rat SCN, but not in other hypothalamic areas. In dipped sections, it was evident that the localization of NMDA-2RC was mostly confined to the dorsomedial part of the SCN. Thus, the rat SCN contains a specific combination of NMDA receptor mRNA subtypes not found in other forebrain structures. These observations are consistent with the hypothesis that glutamate mediates the effect of light on entrainment of the circadian oscillator.