There is increasing evidence that synaptic transmission between retinal ganglion cell axons and neurons in the lateral geniculate nucleus (LGN) is mediated primarily by excitatory amino acids. The goal of this proposal is to examine the role of NMDA and non-NMDA excitatory amino acid receptors on neurons LGN in (a) retinogeniculate transmission through the adult LGN, and (b) the development of retinogeniculate projections. These experiments follow from the hypothesis that NMDA receptors an be used for two distinct tasks in the brain: for regulating the level of postsynaptic activity in normal adult function, and for regulating synaptic connections during development. Specific questions include: (1) Are there NMDA and non-NMDA excitatory amino acid receptors on LGN neurons in adult cats and ferrets? Are these receptors at retinogeniculate synapses or at corticogeniculate synapses? (2) How does blocking these receptor sub-types affect the visual responses of adult LGN neurons? (3) Can NMDA receptors at retinogeniculate synapses, in tandem with cortical inputs on LGN neurons, serve to gate transmission of visual information through the LGN to visual cortex? (4) Are there NMDA and non-NMDA receptors on LGN neurons at early stages of development of the visual pathway? How do these receptors contribute to the excitatory postsynaptic responses of developing LGN cells? (5) How does blockade of NMDA and non-NMDA receptor affect the development of retinogeniculate connections? In particular, what role do these postsynaptic receptors play in two key events in retinogeniculate development: formation of eye- specific layers, and, in ferrets, the formation of on and off sublayers? (6) How are NMDA receptors involved in synaptic potentiation, and hence in the consolidation and elimination of retinogeniculate synapses, during development? The first three questions relate to the adult LGN and will be addressed using (a) extracellular recording and microiontophoresis, and (b) intracellular recording in slices of LGN. The next three relate to the developing LGN and will be addressed using (a) minipump infusion of agonists and antagonists, and (b) intracellular recording in slices of LGN at different ages.
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