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 transmission through metabotropic glutamate receptors (mGluRs) linked to a variety 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 produces a membrane depolarization that inactivates the low-threshold Ca2+ spike, causing a transition from burst to tonic response mode, The excitatory effects of metabotropic receptor activation in the LGN appear to be produced through the receptors linked to phosphoinositide hydrolysis and apparently only through activation of the corticogeniculate pathway, Two mGluRs, mGluR1 alpha (a splice variant of mGluR1) and mGluR5, are linked to the phosphoinositide system. We examined the localization of these receptors with affinity-purified, anti peptide, polyclonal antibodies raised to the C-terminal region of each receptor protein. 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 perigeniculate nucleus, We also examined the ultrastructural localization of immunolabel 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 localized in the dendrites of relay cells, postsynaptic to various terminal types. Of these, terminal profiles normally associated with corticogeniculate inputs predominated, whereas retinal terminal profiles were scarce, Label for the antibody directed against mGluR5 label was prominent 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 appears to have a dominant role in corticogeniculate control of response mode through the feedback glutamatergic pathway from layer VI, whereas mGluR5 is positioned to affect retinogeniculate activation of relay cells through feed forward glomerular interactions.