Abstract
Visual processing in the mammalian brain employs parallel architectures, including the evolutionarily conserved tectopulvinar circuitry that conveys signals from the superior colliculus (SC) to the thalamic pulvinar nucleus. Wide-Field (WF) neurons of the superficial SC serve as the primary computational conduit within this circuit; yet structural and functional dissection of this pathway in mammalian models beyond mice remains limited. Foundational insights into the neurobiological mechanisms of visual processing have been driven largely by extensive rodent work; however, the rodent visual system relies on organizational principles that distinguish it from higher mammals. Tree shrews (Tupaia belangeri), on the other hand, serve as an exceptional model of a primate-like visual system featuring highly specialized structures — including a well-stratified superior colliculus, pulvinar, and six-layered geniculate — making them ideal for interrogating subcortical visual circuitry. However, a major challenge in studying these sophisticated circuits in species beyond rodents is the lack of cell type-specific platforms. This dissertation investigates WF neurons and the associated tectopulvinar circuitry from a structural and genetic perspective. In Chapter II, I addressed a fundamental question: Is there a conserved molecular marker for WF neurons that can be leveraged to gain targeted genetic access across species? Using comparative genomics and epigenomics, I systematically identified one such marker, Cerebellin 2 (CBLN2), and leveraged its promoter to design and validate WF-specific Adeno-Associated Viral (AAV) vectors that enable robust genetic access in both tree shrews and mice. In Chapter III, using these newly developed tools, I characterized the efferent tectopulvinar projection patterns, morphology, and synaptic connectivity motifs of WF neurons. These experiments demonstrated that WF neurons project to the pulvinar via two distinct modes: a topographic pathway and a non-topographic, diffuse pathway. Using anterograde and retrograde tract-tracing, I identified anatomical features that provide evidence for two distinct WF cell subtypes corresponding to these projection modes. I then mapped the afferent connectivity of these cells at the synaptic level using whole-cell 3D reconstruction and at the circuit level using brain-wide retrograde tracing, revealing unique spatial targeting strategies for retinal and cortical excitatory inputs. Finally, in Chapter IV, I expanded the utility of these viral tools by establishing electron microscopy (EM)-compatible intersectional targeting of WF neurons, while also identifying new molecular markers and viral tools for additional collicular outputs, including the tectogeniculate pathway. Collectively, from a methodological standpoint, these studies provide novel, species-agnostic tools to bridge the gap between rodent genetic platforms and higher order models; concurrently, at the circuit level, this dissertation reveals new insights into the structural basis of WF neuron function and its implications for visually guided behaviors.
