Differential localization of NMDA and AMPA receptor subunits in the lateral and basal nuclei of the amygdala: a light and electron microscopic study.

Abstract

Anatomical and physiological studies indicate that the amino acid L-glutamate is the excitatory transmitter in sensory afferent pathways to the amygdala and in intraamygdala circuits involving the lateral and basal nuclei. The regional, cellular, and subcellular immunocytochemical localizations of N-methyl-D-aspartate (NMDA) and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), two major classes of glutamate receptors, were examined in these areas of the amygdala. A monoclonal antibody and a polyclonal antiserum directed against the R1 subunit of the NMDA receptor were used. Each immunoreagent produced distinct distributions of perikaryal and neuropilar staining. Dendritic immunoreactivity was localized primarily to asymmetric (excitatory) synaptic junctions, mostly on spines, consistent with the conventional view of the organization and function of NMDA receptors. Whereas the anti-NMDAR1 antiserum produced sparse presynaptic axon terminal labeling and extensive glial labeling, the anti-NMDAR1 antibody labeled considerably fewer glia and many more presynaptic axon terminals. Labeled presynaptic terminals formed asymmetric and symmetric synapses, suggesting presynaptic regulation of both excitatory and inhibitory transmission. Immunoreactivity for different subunits of the AMPA receptor (GluR1, GluR2/3, and GluR4) was uniquely distributed across neuronal populations, and some receptor subunits were specific to certain cell types. Immunoreactivity for GluR1 and Glu2/3 was predominantely localized to dendritic shafts and was more extensive than that of GluR4 due to heavy labeling of proximal portions of dendrites. The distribution of GluR4 immunoreactivity was similar to NMDAR1: GluR4 was seen in presynaptic terminals, glia, and dendrites and was primarily localized to spines. The presynaptic localization of GluR4 in the absence of GluR2 suggests glutamate-mediated modulation of presynaptic Ca++ concentrations. These data add to our understanding of the morphological basis of pre- and postsynaptic transmission mechanisms and synaptic plasticity in the amygdala.