The long term goal of the proposed experiments is to determine the causes of attention impairment during disease. However, it is first necessary to understand the organization of circuits that may contribute to attention mechanisms in the normal brain. Many studies have implicated the pulvinar nucleus as an area that may regulate visual attention. The rodent lateral posterior (LP) nucleus is a region comparable to inferior regions of the primate pulvinar nucleus. The rodent LP nucleus is innervated by fibers which contain the neuropeptide substance P, a neuromodulator known to facilitate neuronal firing properties. The LP nucleus receives visual input from projection cells within an area of the superior colliculus that is substance P- immunoreactive. A combination of tract tracing, immunocytochemistry, electron microscopy and in vitro electrophysiology will be used to examine the synaptic organization and functional properties of the tecto- thalamic pathway. Concomitant release of substance P with glutamate from tecto-thalamic terminals might enhance and potentiate glutamatergic input from the superior colliculus. Because the LP nucleus projects to the visual cortex, the tecto-thalamic pathway could affect visual attention by modulating cortical circuitry. [unreadable] [unreadable]