(Provided by the applicant) Abstract: During development, cellular processes such as neurite growth and synapse formation sculpt the connectivity of the brain. In the visual cortex, this results in functional neral circuits that allow us to see and understand the world around us. Significant progress has been made in studying neural development and visual processing separately. However, it has been more difficult to link these two aspects into an understanding of how the visual system wires itself up to create the specific receptive field properties that underlie vision. Indeed, we still o not know the developmental mechanisms that create orientation selectivity, the fundamental response property of primary visual cortex. Answering this question requires an approach that can bridge molecular and cellular development with systems visual neuroscience. My previous work demonstrated that the mouse visual cortex is an effective model for studying visual processing, and I have recently established a number of innovative techniques allowing us to study the mouse visual system from single genes and cell types up to visual processing and perception. Here I propose an integrative approach, in which I will apply molecular genetic techniques to manipulate key developmental pathways and neural activity in specific subsets of neurons, use in vivo imaging to assess the impact on both visual response properties and cellular growth and synaptogenesis, and perform behavioral psychophysics to test the effects on visual perception. These studies will provide important insight into the assembly of neural circuits, which underlies both normal brain function as well as numerous developmental disorders. Public Health Relevance: This project addresses the assembly of functional circuits in the visual system, and thus will have direct impact on studies of disease states resulting in blindness or visual impairment. Furthermore, as a general method to elucidate principles of cortical development, our approach should be broadly applicable to a number of developmental disorders, such as dyslexia, autism, and schizophrenia, which are thought to result from aberrant cortical wiring and function.
|Lee, A Moses; Hoy, Jennifer L; Bonci, Antonello et al. (2014) Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion. Neuron 83:455-66|