The midbrain superior colliculus (SC) receives extensive projections from sensory, motor and higher- association cortex, and projects downstream to brainstem motor nuclei. These cortico-tecto-brainstem projections are essential for attention-related motor eye movements. Despite this essential functional role and implications in attention-related disorders, little is known about the organization of cortico-tectal projections or their cell-type specific brainstem outputs. Neuroinformatics tools provide a computational capacity to analyze large-scale connectivity data in a reliable and feasible way to reveal novel connectivity organization networks. Previous studies reveal that cortical subnetworks topologically project to the striatum as functional domains. This suggests that cortico-tectal projections may also be organized into functional domains, and then descend to control downstream motor networks. Though classic tracers provide a wealth of input/output information of the SC, they cannot reveal synaptic specific connections. To reveal these connections and characterize their morphological properties, recently developed state-of-the-art rabies virus tracing methods and cutting-edge microscopy imaging provide new tools to elucidate specific pathways. The goal of this study is to construct a comprehensive wiring diagram of cortico-tecto-brainstem circuits that will be presented as an online resource to the scientific community.
Specific Aim 1 will assemble a comprehensive connectivity projection map from the neocortex to the superior colliculus using classic anterograde/retrograde tracing techniques with neuroinformatics tools as part of the Mouse Connectome Project (www.MouseConnectome.org). This data will set an essential structural foundation to facilitate the study of specific attention-related circuits by revealing the organization of distinct functional subnetworks.
Specific Aim 2 will define retrosplenial cortex (RSP) and anterior cingulate area (ACA) projections to distinct SC cell-types based on their anatomical locations, projection targets and neuronal morphologies. To define these cell types, this aim will use a monosynaptic rabies viral tracing method to map the synaptic connectivity between cortico-tectal inputs and brainstem- projecting SC neurons. The additional use of Lightsheet microscopy, SWITCH and 3D-reconstruction techniques utilized in pursuit of these aims render this project an ideal training venue. These studies will provide a more comprehensive foundation of cortical network organization within the SC that can also serve as a cross-species reference. Under the guidance of Dr. Hongwei Dong and colleagues in the Mouse Connectome Project, I will learn to perform high-quality histology, imaging and connectivity data analysis of SC neural networks. The mentorship and technical expertise I will acquire under this training grant will contribute greatly to my overall goal of becoming an independent neuroscientist studying detailed brain architecture.
The superior colliculus (SC) is a multisensory integration structure that plays a role in mediating attention, saccade eye-movements, and orienting behaviors. The goal of this project is to assemble a detailed connectivity map of the cortical inputs to distinct brainstem-projecting SC neuron cell types. This proposal will provide me with training in cutting-edge neuroanatomical techniques, and the resulting connectivity map will serve as an essential resource for the scientific community toward investigations of disease connectopathy in attention deficit hyperactivity disorder and autistic spectrum disorders.
