PROJECT SUMMARY (ABSTRACT) The long-term goal of the proposed research is to understand the neural mechanisms underlying the control of motor output under normal and pathological conditions. We examine here how functional circuitry in the superior colliculus (SC), a bilateral midbrain structure known to be important for orienting behaviors, contributes to decisions about movements. The central hypothesis is that competition between spatial targets represented in the two SCs is mediated by commissural SC neurons that engage local inhibition. We test this hypothesis by recording and manipulating the activity of specific classes of neurons in freely-moving transgenic mice performing olfactory-cued spatial choice tasks. Aim 1 will examine how the activity within one SC of excitatory and inhibitory SC neurons, examined in separate sets of mice, underlies spatial choice. Aim 2 will examine how this activity, and the influence of inhibition on excitatory SC activity within the same SC, is modulated by competition between spatial targets represented by the two SCs. Aim 3 will examine the role of commissural SC neurons in mediating this competition between spatial targets. If successful, the overall impact of our proposal will be the elucidation of how excitatory and inhibitory SC neurons interact – within one SC and between the two SCs – to mediate spatial choice, an important form of decision making. In addition to testing the specific hypotheses proposed here, the model we develop will make possible future research into how other genetically-defined networks of neurons contribute to decisions about movements. Ultimately, understanding normal motor control can contribute to improving therapies for movement disorders, such as Parkinson's disease.