Establishing how features of the visual world are represented in the activity of cortical circuits, and how these representations are constructed during development remain fundamental challenges for visual neuroscience and are central to understanding the neural basis of visual perception. A critical function of circuits in primary visual cortex is the integration of the inputs from the two eyes to create a single binocularly aligned columnar representation of stimulus features such as the orientation of edges and their direction of motion. This alignment is evident at the scale of columns, and at the scale of individual neurons: visual stimuli presented to either eye yield highly similar responses at both scales, giving rise to our coherent binocular perception of the world. Our studies during the previous period of support have revealed a surprising new and critical role for visual experience in the development of binocularly aligned columnar representations in ferret visual cortex. Prior to natural eye opening, visual stimulation thru either eye evokes highly structured columnar maps of orientation preference, but there are conspicuous mismatches in the spatial organization of these maps that reflect misalignment in the orientation preference of the inputs that individual neurons receive from the two eyes. Shared binocular experience immediately following eye opening is necessary to drive changes in the orientation preference of individual neurons that achieve a single binocularly unified representation. The goal of this proposal is to employ new technologies that we have developed that make it possible to visualize the functional organization of excitatory synaptic inputs to individual neurons in order to probe the mechanisms responsible for this alignment process. We start in Aim 1 by examining the synaptic basis for binocular integration in the mature visual cortex, combining 2-photon in vivo imaging of calcium signals with post-hoc electron microscopy to elucidate how the numbers, strength, and the spatial arrangement of functionally characterized synapses contribute to the binocular response properties of individual layer 2/3 neurons.
In Aim 2, we examine the functional synaptic architecture of binocular integration early in development and use chronic imaging techniques to probe changes induced by the onset of visual experience.
In Aim 3 we combine in vivo imaging with expansion microscopy to explore how 2 major sources of inputs to layer 2/3?feedforward inputs from layer 4, and horizontal connections from other layer 2/3 neurons--contribute to the mature pattern of binocular integration and to the development of binocularly aligned representations. Taken together, we believe these experiments will yield a wealth of new insights into the synaptic basis for binocular integration and the experience-dependent mechanisms that achieve aligned representations in visual cortex.
Despite years of study, we do not understand the developmental mechanisms that are responsible for bringing together the inputs from the two eyes to create a single coherent cortical representation of stimulus features. The proposed experiments will provide new insights into the synaptic basis for binocular integration, and the underlying developmental mechanisms that guide this alignment process?insights that are critical for addressing numerous visual, neurological, and psychiatric disorders that are grounded in cortical circuit dysfunction.
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| Scholl, Benjamin; Wilson, Daniel E; Fitzpatrick, David (2017) Local Order within Global Disorder: Synaptic Architecture of Visual Space. Neuron 96:1127-1138.e4 |
| Lu, Rongwen; Sun, Wenzhi; Liang, Yajie et al. (2017) Video-rate volumetric functional imaging of the brain at synaptic resolution. Nat Neurosci 20:620-628 |
| Wilson, Daniel E; Smith, Gordon B; Jacob, Amanda L et al. (2017) GABAergic Neurons in Ferret Visual Cortex Participate in Functionally Specific Networks. Neuron 93:1058-1065.e4 |
| Wilson, Daniel E; Whitney, David E; Scholl, Benjamin et al. (2016) Orientation selectivity and the functional clustering of synaptic inputs in primary visual cortex. Nat Neurosci 19:1003-9 |
| Dimidschstein, Jordane; Chen, Qian; Tremblay, Robin et al. (2016) A viral strategy for targeting and manipulating interneurons across vertebrate species. Nat Neurosci 19:1743-1749 |
| Smith, Gordon B; Fitzpatrick, David (2016) Viral Injection and Cranial Window Implantation for In Vivo Two-Photon Imaging. Methods Mol Biol 1474:171-85 |
| Smith, Gordon B; Whitney, David E; Fitzpatrick, David (2015) Modular Representation of Luminance Polarity in the Superficial Layers of Primary Visual Cortex. Neuron 88:805-18 |
| Smith, Gordon B; Sederberg, Audrey; Elyada, Yishai M et al. (2015) The development of cortical circuits for motion discrimination. Nat Neurosci 18:252-61 |
| Meng, Yicong; Tanaka, Shigeru; Poon, Chi-Sang (2012) Comment on ""Universality in the evolution of orientation columns in the visual cortex"". Science 336:413; author reply 413 |
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