Friday, April 26, 2024
4/26/2024
Summary Experience with the external world is essential for fine-tuning immature sensory circuits during critical periods in development. In visual systems, experience regulates the alignment of visual information from the ipsilateral and contralateral eye onto neurons in the binocular primary visual cortex (bV1). At the onset of the critical period for binocular vision, bV1 neurons respond to distinct orientation preferences to each eye. With visual experience, synaptic inputs from each eye get modified, and bV1 neurons develop matching orientation preferences. Disrupting visual experience during this critical period, however, can elicit severe impairments in binocular vision, causing amblyopia. It remains unclear how synaptic inputs are modified to regulate the development of orientation matching in bV1 neurons. Hebbian and heterosynaptic plasticity are mechanisms of experience- dependent plasticity that modify synaptic inputs based on the correlation of pre- and postsynaptic neuronal responses and on the activity of neighboring synapses, respectively. Together, these two mechanisms can shape the selectivity of neuronal responses by strengthening synapses that are correlated with the postsynaptic neuron or with synaptic neighbors, and by weakening those that are uncorrelated. I hypothesize that Hebbian and heterosynaptic mechanisms regulate the alignment and plasticity of eye-specific inputs onto bV1 neurons over the critical period. To test this hypothesis, I will chronically image the visual responses of the neuronal soma and of dendritic spines using in vivo two-photon calcium imaging to track eye-specific inputs on L2/3 bV1 neurons. I will then map the synaptic composition of the physiologically identified dendritic spines post hoc by implementing a novel tissue expansion technology called Magnified Analysis of the Proteome (MAP) that allows for super-resolution imaging of intact tissue. I will combine these cutting-edge technologies in my two aims to delineate how the alignment of somatic orientation preference arises through synaptic remodeling of eye-specific inputs. In Aim 1, I will characterize the functional, structural, and molecular properties of eye-specific inputs across development to determine whether Hebbian and heterosynaptic plasticity is taking place during somatic orientation matching. In Aim 2, I will deprive the contralateral eye of visual experience using monocular deprivation (MD) to determine how disruptions in binocular vision impact eye-specific inputs on bV1 neurons. Together, these experiments will answer fundamental questions on the nature of experience-dependent plasticity in the binocular visual cortex. Furthermore, these studies will provide critical insight into the synaptic basis of amblyopia, as well as neurodevelopmental disorders that are induced by synaptic dysfunction.
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