The overall goal of this research plan is to understand the role of the basal ganglia (BG) and superior colliculus (SC) in saccadic eye movement choice and decision-making. This requires developing an in vitro brain slice model with which we will extend our recent in vivo results and investigate the biophysics of a circuit involved in choice and decision-making. The ultimate goal is to link the properties of neurons and their circuits to behavior in order to elucidate the role of the SC and the BG in eye-movement related cognitive processes. We have three Specific Aims: 1) Map response patterns across the SC. Voltage imaging will be used to map the spatial patterns of signal spread following electrical stimulation in the superficial SC (sSC) and intermediate SC (iSC). This aim will provide a basic assessment of the spatial extent of both intra- and inter-laminar circuitry within the SC. 2) Evaluate inhibition and excitation in SC activity patterns. In this aim we will test for the existence of three specific interlaminar pathways: an excitatory pathway arising from the sSC extending to the iSC, an inhibitory pathway arising from the iSC and extending into the sSC and an excitatory pathway arising from the iSC and extending into the sSC. We will use voltage imaging in conjunction with patch clamping to study responses to sSC and iSC stimulation, and resolve these responses into contributions mediated by glutamatergic and GABAergic synapses. Experiments with synaptic receptor agonists and antagonists will assess the role of glutamatergic and GABAergic transmission in both intra- and interlaminar circuits. 3) Determine the influence of BG output on the response pattern across the SC. The experiments of this aim will test the hypothesis that translation of visual information from sSC into motor information in iSC is modulated by inhibition from the substantia nigra pars reticulata of the BG. We will apply electrical stimulation in the nigra to determine how the nigra modulates SC responses to sSC and iSC stimulation. Because the BG is implicated in many neurological and psychiatric disease states, the results of our experiments should lead to important insights into the functioning of these circuits and the biophysical mechanisms underlying complex behavioral and cognitive processing in both health and disease.