Control of thalamic circuits by a higher-order cortical area

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Project Summary/Abstract This project will investigate how a higher-order cortical area modulates thalamic activity to shape sensory perception. Almost all sensory information passes through the thalamus en route to the cortex, and traditionally the thalamus has been considered a simple relay. However, the neocortex also provides robust projections to the thalamus, with descending corticothalamic (CT) axons outnumbering ascending thalamocortical (TC) axons by about 10:1. The anatomy alone implies that thalamic functions are complex, and that the cortex likely exerts a substantial influence on the thalamus and, through this, on its own inputs. CT communication plays a role in conditions such as epilepsy, schizophrenia, and attention deficit disorders. A thorough understanding of CT function has remained elusive, and most studies of CT pathways have explored unimodal primary sensory areas or the prefrontal cortex. Similar motifs in the anatomy and physiology of these circuits have emerged, raising the questions: Does every cortical area have a similar pattern of feedback to the thalamus? How are diverse CT pathways relevant to vastly different types of behavior? The parahippocampal cortex (called the postrhinal cortex, POR, in rodents), is a polymodal association area and the principal source of visual information to the hippocampus. The POR is heavily interconnected with the pulvinar nucleus of the thalamus (also known as the lateral posterior nucleus in rodents). POR and pulvinar have both been implicated in networks mediating visual attention, yet almost nothing is known about the structure and function of CT pathways from POR to pulvinar. The central goal of this proposal is to determine how top-down projections from cortical area POR influence the functions of the thalamic pulvinar nucleus at the level of cellular, synaptic, and circuit mechanisms. Aim 1 is a deeper understanding of the anatomy of the CT projection, including their origins in POR and their projection patterns in pulvinar and neighboring inhibitory circuits. For this I will utilize viral transduction strategies, immunohistochemistry, and imaging. Aim 2 is to characterize the intrinsic and synaptic physiological properties of the POR-to-pulvinar pathway using in vitro whole-cell recordings, optogenetics, and Cre-expressing mouse lines to target projections in a cell- and layer-dependent fashion. Aim 3 is to explore the functions of this pathway in awake animals by recording single-unit and local field potential activity in the POR and pulvinar during visual stimulation and optogenetic manipulation of the CT pathway. The applicant will receive first-rate training from two Co-Sponsors with complementary expertise in cortico- thalamic and corticohippocampal circuits, and in a range of techniques for cellular neurophysiology, anatomy, systems, and behavioral neuroscience. The applicant’s research will reveal new cellular, circuit, and functional features of corticothalamic control exerted by higher-order cortical area on the visual thalamus.