ULTRASTRUCTURAL-LOCALIZATION SUGGESTS THAT RETINAL AND CORTICAL INPUTS ACCESS DIFFERENT METABOTROPIC GLUTAMATE RECEPTORS IN THE LATERAL GENICULATE-NUCLEUS

Glutamate has an important neuromodulatory role in synaptic transmissi on through metabotropic glutamate receptors (mGluRs) linked to a varie ty of G-protein-coupled second messenger pathways. Activation of these receptors on relay cells in the lateral geniculate nucleus (LGN) with the agonist trans(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid pr oduces a membrane depolarization that inactivates the low-threshold Ca 2+ spike, causing a transition from burst to tonic response mode, The excitatory effects of metabotropic receptor activation in the LGN appe ar to be produced through the receptors linked to phosphoinositide hyd rolysis and apparently only through activation of the corticogeniculat e pathway, Two mGluRs, mGluR1 alpha (a splice variant of mGluR1) and m GluR5, are linked to the phosphoinositide system. We examined the loca lization of these receptors with affinity-purified, anti peptide, poly clonal antibodies raised to the C-terminal region of each receptor pro tein. Under examination with the light microscope, we found that both types of receptors are present in the geniculate neuropil and in that of the overlying thalamic reticular nucleus, including the perigenicul ate nucleus, We also examined the ultrastructural localization of immu nolabel with the electron microscope, using a postembedding immunogold marker to identify terminals, dendrites, and somata that contain GABA , Label for the antibody directed against mGluR1 alpha was primarily l ocalized in the dendrites of relay cells, postsynaptic to various term inal types. Of these, terminal profiles normally associated with corti cogeniculate inputs predominated, whereas retinal terminal profiles we re scarce, Label for the antibody directed against mGluR5 label was pr ominent in inhibitory F2-terminal profiles associated with the retinal input to relay cells. In the perigeniculate nucleus, both mGluRs were localized to dendrites. The distribution of the two phosphoinositide- linked mGluRs in the LGN suggests very different functional roles for the two receptor types. We conclude from these data that mGluR1 appear s to have a dominant role in corticogeniculate control of response mod e through the feedback glutamatergic pathway from layer VI, whereas mG luR5 is positioned to affect retinogeniculate activation of relay cell s through feed forward glomerular interactions.