Direct and Transthalamic Pathways between Primary and Secondary Visual Cortex

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PROJECT SUMMARY / ABSTRACT While the thalamus' role in relaying sensory information to the cortex is well established, much less is known about its role in ongoing cortical processing. The majority of the thalamus by volume is made up of higher- order (HO) thalamic nuclei, which appear to actively contribute to functions that are traditionally attributed to the cortex alone, including attention [3]–[10]. HO thalamic nuclei receive their main driving input from cortex and are hypothesized to form critical cortical-thalamo-cortical or transthalamic circuits that provide indirect links between cortical areas. Indeed, it appears cortical areas are often connected by parallel direct and transthalamic pathways [1]. Despite an increased appreciation for the significance of thalamalcortical interactions, it is still not clear what the nature of the information carried by each pathway is, or what the purpose of this parallel pathway organization is. The goal of the proposed in vivo experiments is to determine the relative contribution of the direct and transthalamic pathways from V1 to V2 on responses in V2. To do so, we use DREADD methodology to selectively target and suppress each source of input from V1 while using Ca2+ imaging to record visually evoked activity in large populations of V2 neurons before and after inactivation. The effects of these manipulations are investigated at both the single-cell and systems level. While research on corticocortical communication has primarily focused on direct projections, the information conveyed by these direct pathways also remains unclear. For example, previous attempts to define the function of the direct input from V1 to V2 relied on total suppression of V1, which would reduce all V1 outputs including transthalamic pathways. In the visual system, the HO thalamic nuclei Pulvinar appears to facilitate the transfer of information between cortical areas [35], possibly by altering functional connectivity both within and between brain regions [53,54,58,59]. HO thalamic nuclei have also been linked to deficits associated with a number of psychiatric disorders. For example, atypical corticocortical communication via transthalamic circuitry is hypothesized to contribute to sensory processing deficits associated with disorders such as schizophrenia [22,25]. Thus, the results of the proposed experiments will provide insight into the flow of information processioning in the central nervous system and may reveal circuit-level context for interpreting cognitive deficits associated with HO thalamic nuclei, such as those seen in Schizophrenia.