Selective distribution of the NMDA-R1 glutamate receptor in astrocytes and presynaptic axon terminals in the nucleus locus coeruleus of the rat brain: An immunoelectron microscopic study

Abstract

The regional and cellular distribution of the different classes of excitatory amino acid receptors with respect to the noradrenergic neurons of the nucleus locus coeruleus (LC) are unknown. We therefore combined immunoperoxidase labeling for the R1 subunit of the N-methy-D-aspartate (NMDA) receptor with immunogold-silver localization of the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), in single sections through the rat LC to determine the subcellular localization of this glutamate receptor subtype with respect to the noradrenergic neurons. At the light microscopic level, there was light to moderate labeling for the NMDA-R1-like (li) receptor in the caudal pole of the LC and dense labeling in the dorsolateral aspect of the LC adjacent to the superior cerebellar peduncle. In the rostral pole of the LC which is enriched with noradrenergic dendrites, significant overlap between both immunoreactivities could be observed. At the ultrastructural level, immunoperoxidase labeling for NMDA-R1 was selectively distributed in astrocytic processes and within presynaptic axon terminals but was rarely seen in catecholamine-containing somata or dendrites. Peroxidase labeling for NMDA-R1, however, was occasionally observed in dendrites in the rostral pole of the LC. Most of these dendrites lacked detectable levels of TH, although TH immunoreactivity was apparent in the neuropil. Dendrites containing NMDA-R1-li immunoreactivity often received asymmetric (excitatory-type) contacts from unlabeled terminals. NMDA-R1-li-immunoreactive axon terminals usually contained small clear, as well as large dense-core vesicles and were often apposed to unlabeled dendrites, axon terminals and/or glial processes. These results provide the first ultrastructural evidence that NMDA-R1-li immunoreactivity is selectively distributed within astrocytic processes and presynaptic axon terminals within the LC.

Localization of NMDA receptors in the cerebral cortex: a schematic overview

“…These data suggest that NMDA receptors play a role in the regulation of GABAergic transmission. Overall, these data are consistent with previous demonstrations that presynaptic NMDA receptors contribute to NMDA-mediated phenomena in other regions of the nervous system (58)(59)(60)(61)(62)(63)(64).…”

NMDA Receptors Mediate Neuron-to-Glia Signaling in Mouse Cortical Astrocytes

“…Finally, it remains unclear whether the neuronal-to-glial communication mediated by NMDA receptors occur only in cortex, or they may also be present in other brain regions. The NMDA receptor proteins were predominantly identified in cortical astrocytes (Conti et al, 1997 but not in hippocampus (Krebs et al, 2003); there are some indications for NMDA receptors expression in astroglial cells in nucleus locus ceruleus (Van Bockstaele and Colago, 1996). Interestingly, reactive gliosis induced by ischemia led to an appearance of NMDA receptor subunits in hippocampal astrocytes (Gottlieb and Matute, 1997;Krebs et al, 2003).…”

“…Subunits of NMDA receptors (NR1 and NR2A/B) and expression of NMDA receptor mRNA were detected in astrocytes by immunohistochemistry, in situ hybridization, and PCR (Conti et al, 1996(Conti et al, , 1997Van Bockstaele and Colago, 1996;Schipke et al, 2001). Several functional studies demonstrated NMDAmediated currents and NMDA-induced [Ca 2ϩ ] i responses in cultured astrocytes (Kondoh et al, 2001) and in astrocytes in situ (Muller et al, 1993;Shao and McCarthy, 1997;Ziak et al, 1998;Schipke et al, 2001).…”

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

“…Stimulation of NMDARs results in, at least in part, the activation of nNOS. The LC region contains NMDAR (Allgaier et al, 2001;Shaw et al, 1992;Van Bockstaele and Colago, 1996), neuronal nitric oxide synthase (nNOS)-positive neurons (Cuellar et al, 2000;Karolewicz et al, 2004;Xu et al, 1994), and guanosine 3 0 ,5 0 cyclic monophosphate (cGMP) (Vulliemoz et al, 1999;Xu et al, 1998), suggesting the existence of a glutamate/nitrergic transduction pathway. The exact cellular localization of these glutamate/nitrergic signaling proteins within the human LC is still unknown.…”