Project Summary The parafascicular nucleus is a major nucleus in the so-called intralaminar group. Although it is traditionally considered part of the reticular activating system and thought to play a role in arousal and attention, its contributions to behavior are still poorly understood. Much of the work on the Pf was done in primates before the development of modern intersectional strategies for selective cell type targeting and neural circuit dissection. This proposal aims to elucidate the computational functions of specific components of the Pf circuit, and to determine how this circuit can be used for the control of attention and action selection. Preliminary results indicate that the Pf plays a key role in rapid action generation, which appears to be mediated by direct excitatory inputs from the deep/intermediate layers of the superior colliculus. Two populations of Pf projection neurons target different downstream structures and have distinct behavioral functions. We hypothesize that Pf projections to the subthalamic nucleus are especially important for fast action initiation that bypasses the canonical basal ganglia circuitry, where as the well-known Pf projections to the striatum is not needed for action initiation, suggesting that the Pf-basal ganglia pathway has a distinct function. A highly integrative approach will be employed, combining 1) Motion capture for continuous behavioral quantification in 3D; 2) wireless in vivo recording from single neurons; 3) optogenetic manipulation of defined neuronal populations; 4) 1-photon calcium imaging of genetically defined individual neurons; and 5) quantitative operant behavioral assays. These tools will be used to determine how the Pf processes inputs from the midbrain and uses this information to guide action selection via distinct output projections to the STN and striatum.