In development, there are brief windows in time when circuits in the brain can be altered by an individual's experience. The role of these ?critical periods? is poorly understood. However, it is known that maladaptive experience during a critical period leads to miswiring of circuitry, causing permanent deficits. Neurodevelopmental disorders are triggered by abnormalities during brain development, which may result from a defect in the mechanisms that regulate the critical period. These disorders are most often characterized by social and cognitive symptoms, however they often present with sensory deficits including hypersensitivity to external stimuli and poor sensory integration. The Chen lab studies neural development in the visual system. The main focus of the lab is the development of the retinogeniculate synapse, the connection between retinal ganglion cells (RGCs) and the dorsal lateral geniculate nucleus (dLGN). This synapse is readily accessible in a slice preparation, and is known to undergo pruning and strengthening of inputs during early developmental refinement. Recently, the lab has defined a late thalamic critical period between postnatal days 20-32 when visual deprivation or alterations to cortical feedback causes a recruitment of retinal fibers onto dLGN neurons. These findings highlight an important role for cortical feedback in visual development, which has canonically been described to occur in a feed-forward progression. Moreover, the corticothalamic projections providing the feedback signal are the last component of the circuit to be established in development, making them prime candidates for regulators of sensory symptoms associated with neurodevelopmental disorders, which have a relatively late onset. Yet, how increased convergence to the dLGN affects signal processing is unclear. Each retinal ganglion cell tiles a region of visual space, and carries distinct information (luminance, contrast, orientation) to a relay neuron in the dLGN. It is thought that the composition of the RGC inputs gives rise to mature signal processing in the dLGN such as spatially restricted receptive fields, and selectivity for several features in the visual scene including orientation and direction in mice. Increasing retinal convergence by altering cortical feedback in the thalamic critical period might recruit RGCs that are tuned to different receptive field features, thereby diluting selectivity and altering binocularity. The goals of this proposal are to characterize how cortical feedback affects the development and plasticity in the dLGN, and to determine how synapses in the corticofeedback circuit are altered by experience. Understanding the role of cortical feedback in visual development and processing will shed light on how feature selectivity is controlled to produce mature visual function. Moreover, it may provide a framework for studying similar circuits in brain regions that control more complex, social and cognitive behaviors
Sensory processing is essential for interacting with the world around us, and is shaped by developmental critical periods when circuits in the brain are sculpted by experience. Recent lines of evidence suggest that deficits in sensory perception and integration associated with neurodevelopmental disorders may be caused by aberrant refinement of circuits during later critical periods of development. In this project, I will test a hypothesis that disruptions to the projection from the cortex to the thalamus during a late critical period can alter circuits that are important for visual processing.
