Various functional properties of visual cortical neurons, as usually measured by their output responses, undergo progressive developmental maturations, the process of which is often susceptible to experience-dependent modifications during a critical period (CP). The functional changes of neuronal responses during normal development or induced after specific sensory experience can be caused by changes in the functional cortical synaptic circuitry, the nature of which has remained largely unknown. This is mainly due to a shortage of direct measurements of sensory-evoked excitatory and inhibitory synaptic inputs to developing cortical neurons, techniques for which remain very challenging. In this project, we will probe into functional synaptic circuits in the developing mouse visual cortex by combining several cutting-edge approaches, including in vivo whole-cell voltage-clamp recording, two-photon imaging guided patch recording, Ca2+ imaging and optogenetic manipulations. We will focus on visual receptive field (RF) and orientation selectivity (OS) properties in layer 4 of the primary visual cortex (V1).
In Aim1, we will determine the progression of RF development by recording spike responses of single neurons in pre-CP, during CP and post-CP stages. We will then carry out voltage-clamp recordings to elucidate excitatory and inhibitory synaptic inputs underlying the RF. We will also carry out imaging guided recording and Ca2+ imaging of genetically labeled inhibitory neuron subtypes, in particular, parvalbumin (PV) positive neurons, to elucidate how their RFs are developed.
In Aim2, by optogenetically activating cortical inhibitory neurons, we will isolate the thalamocortical input (and derive the intracortical input) to an excitatory neuron by silencing spiking of cortical excitatory neurons. W will investigate how developmental changes of these two components of cortical excitation contribute to the maturation of OS. By mapping visual RFs of the thalamocortical input, we will also investigate how developmental changes in specific spatial arrangements of thalamic inputs lead to maturation of their orientation tuning. Finally, for both aims, we will test whether the observed developmental processes are shaped by visual experience by comparing animals reared in darkness with age-matched animals reared normally. This line of research should greatly enhance our understanding of synaptic circuitry mechanisms underlying normal cortical functional development as well as plasticity induced by visual deprivation.
This project investigates the excitatory and inhibitory synaptic circuit mechanisms underlying normal development of visual cortical functions as well as cortical plasticity after abnormal experience such as visual deprivation. Understanding how the organization of synaptic circuits changes during development is necessary to identify mechanisms that go awry in developmental diseases. The work proposed here bears directly on a key theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in cortical circuits.
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