This is an excellent application to investigate the role of metabotropic glutamate receptors in visual information processing, and in thalamic functioning in general. Thalamic neurons can operate either in a burst or tonic response mode, and there is evidence that the switching between these is regulated in part by mGluR's. In the lateral geniculate nucleus, only two types of mGlur's are present, mGlur1 and R5, and these appear to have completely distinct patterns of localization, one postsynaptic to corticogeniculate terminals and the other on the dendrites of inhibitory interneurons that synapse with X cells. Through the use of drugs that activate or inhibit either one type of mGluR or both, along with selective GABA receptor antagonists, studies will be done in vivo and in vitro to investigate the role of the two types ofmGluRs in controlling LGN neuronal responses. Specific hypotheses are put forward on the predicted effects of various drugs on neuroonal responses properties. In particular, specific drugs are expected to alter the response properties of all relay cells, and other are expected to alter the response of inhibitory interneurons, and as a consequence of this, theproperties of the X cells onto which they synapse. Activation of the two types of mGluR's is expected to have opposite effects on X cells, by virtue of the involvement of the inhibitory interneurons. MgluR1 effects are thought to be mediated by altering a K conductance, and this will be examined as well. In vivo experiments will verify the sources of inputs that activate the two types ofmGluR's.
