Project Summary In most mammals, the dorsal thalamus is considered to be a relay station for sensory signals propagating from periphery to cortex. Indeed, first order (FO) nuclei receive their input from the periphery (e.g. retinal input to the lateral geniculate nucleus or LGN) and send their principal output to cortex. By volume, however, the majority of the thalamus in primates consists of higher-order (HO) nuclei, defined as receiving their principal input from cortex. Despite their dominance in the thalamus, the function of HO nuclei has yet to be conclusively elucidated. One hypothesis is that HO nuclei play a key role in the communication between cortical fields given their patterns of interconnectivity with cortex. These transthalamic corticocortical circuits are commonly paralleled by direct corticocortical connections between the same two cortical areas. The nature and function of the signals carried by HO nuclei remain largely unknown. The goal of the proposed experiments in macaque monkeys is to determine if and how it shapes neuronal responses in primary and higher order cortical areas, and establish its role in touch-mediated behaviors. To this end, we will study the response properties of sHO neurons while animals perform one of two tasks – a discrimination task that relies heavily on higher order cortical processing and a detection task that does not. Then, we will assess the consequences of silencing the sHO nucleus both on the responses of neurons in different cortical fields and on the animal’s behavior. INTELLECTUAL MERIT. The expansion of the neocortex is the hallmark of human evolution, endowing us with language, fine motor control, and increased cognitive capacity. With the relative expansion of the neocortex, primary sensory nuclei of the thalamus have remained relatively stable in size while higher order (HO) thalamic nuclei have expanded. We hypothesize that this relative expansion is closely associated with the expansion of cortex because the function of these nuclei is to mediate communication between different cortical fields. The role of this transthalamic circuit remains largely unknown, a gap we will begin to fill. BROADER IMPACT. In addition to their contribution to basic science, the results will also have important clinical implications. Indeed, many cognitive defects have been associated with HO thalamic relays. For instance, schizophrenia presents a noteworthy thalamic pathology based on MRI and postmortem anatomy: HO nuclei (e.g., the mediodorsal nucleus and Pulvinar) are shrunken with neuronal loss but FO nuclei appear normal. Schizophrenia may thus disrupt transthalamic circuits, among other effects and the cognitive defects in schizophrenia may be at least partly related to pathology in the transthalamic system. Generally speaking, this new hypothesis of FO and HO thalamic relays may prove a useful hypothetical framework against which to consider thalamic deficits in various clinical conditions.