Localization of NMDA receptor subunit mRNAs in the rat locus coeruleus

N-Methyl-D-aspartate (NMDA)-activated ionotropic glutamate receptors in the CNS are thought to play a crucial role in cognitive processes, neurological disorders as well as in progressive neurodegenerative diseases. In spite of the overwhelming evidence for the existence of structurally different subunits of NMDA receptors in the CNS, the functional relevance of this heterogeneity is still poorly understood. A first step in this direction is to demonstrate the receptor composition in well-characterized transmitter-specific neuronal populations, such as the noradrenergic neurons of the rat locus coeruleus (LC). LC neurons may play a key role in the regulation of vigilance, attention, learning and memory, as well as anxiety and are affected in neurodegenerative disorders. In this study we examined, by means of in situ hybridization with 35S-labelled oligodeoxynucleotide probes, the distribution of mRNAs encoding the splice variants of the NMDAR1 subunit as well as four NMDAR2 subunits (A-D) in the rat LC. Identified neurons express mRNAs encoding several NMDAR1 subunit isoforms (4a, 2a > 2b, 4b) as well as NMDAR2 subunits (2B > 2D), whereas other transcripts (1a,1b,3a,3b,2A,2C) were not detected. These findings suggest that NMDA receptors in the LC are composed of unique combination(s) of subunits, e.g. 4a-2B, of as yet unknown stoichiometry. Whether the identification of this potential drug target can be exploited, e.g. in the development of new anxiolytics, antidepressants, or neuroprotective agents, awaits further investigations.