Differential distribution of intracellular glutamate receptors in dendrites

Abstract

Glutamate receptors are synthesized in the cell body and transported in intracellular compartments to the target synapse. The objective of the present study was to analyze the intracellular pool of glutamate receptors and determine whether the intracellular pool was related to the synaptic distribution of the receptors. As a model system, we chose the fusiform cell of the dorsal cochlear nucleus for which we have previously demonstrated that receptors are selectively targeted to synapses on apical and basal dendrites. A combination of retrograde tracing and postembedding immunogold labeling was used to quantify intracellular receptors in segments of apical and basal dendrites. Immunolabeling for GluR4 and mGluR1α is present at synapses on basal dendrites but not on apical dendrites, whereas immunolabeling for GluR2/3 is present at both populations of synapses. In the analysis of intracellular pools, we find that GluR2/3 is equally distributed in apical and basal dendrites, whereas GluR4 and mGluR1α are more concentrated in basal dendrites than in apical dendrites. These findings indicate that the distribution of intracellular receptors is related to that of synaptic receptors and suggest that a mechanism exists in neurons to target proteins to dendritic domains soon after synthesis. We found no evidence for the existence of a pool of intracellular receptors, which could represent a receptor reserve, near the postsynaptic density. Receptors were often found in clusters associated with tubulovesicular membranes of the endoplasmic reticulum, identified with immunoglobulin binding protein (BIP) or calnexin, suggesting that this organelle is involved in receptor transport in dendrites.