Project Summary Intracellular recording from sensory cortex provides a window into the synaptic inputs that shape spiking responses of individual cortical neurons, but until recently, this powerful technique has been limited to anesthetized animals. By combining the unique expertise from our laboratories, we have developed a novel technique that allow us to conduct, on a routine basis, reliable, whole-cell intracellular recording in primary visual cortex (V1) of awake, behaving macaque monkeys. We combine intracellular recording with an array of concomitant measurements that provide access to the state of the local network in which the neuron is embedded as well as to the internal state of the animal. Using these techniques, we have access to both subthreshold (membrane potentials, representing input) and suprathreshold (spikes, representing output) responses of individual cortical neurons, while also utilizing the precise control of visual stimulation and the subject’s behavioral state afforded by behaving primates. Our ability to perform intracellular recording in awake, behaving primates opens the door to addressing three fundamental questions with respect to the circuit-level mechanisms that mediate visual perception: (1) what are the nature, sources, and behavioral consequences of the large neural variability of sensory cortical neurons, (2) what is the contribution of internal state fluctuations to this variability, (3) what circuit models can account for the observed neural variability during spontaneous and evoked responses? To address these questions, in Aim 1 we will study the quantitative relationship between sub- and suprathreshold activity during spontaneous and stimulus-evoked responses in V1 of fixating monkeys. This will allow us to test the generality of previous findings from anesthetized animals. In Aim 2, we will examine the relationship between the activity of single V1 neurons and perceptual decisions in monkeys that are engaged in a demanding visual detection task. Specifically, we will examine how sub- and suprathreshold responses are altered by changing the attentional and motivational states under which the stimulus is presented. Finally, in Aim 3 we will test a novel set of circuit models that can account for our observed results and guide future experiments.