Plasticity of the Retinogeniculate Synapse

Boston Children'S Hospital, Boston MA

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Abstract

ABSTRACT There is growing evidence that subcortical regions of the early visual pathway are not simple relays of primary visual information but play a greater role in visual system processing and plasticity than previously acknowledged. One such example is the primary visual thalamus, the dorsal lateral geniculate nucleus (dLGN). Studies across different species have demonstrated that circuits in this nucleus can change over development and even in the adult. The Chen Lab uses the mouse visual system as an experimental model to study synaptic plasticity of the connection between retinal ganglion cells (RGCs) and thalamocortical (TC) neurons in the dLGN. Our studies uncovered a late developmental period when visual deprivation can alter the strength and number of convergent retinal inputs onto TC neurons. We refer to this window of experience-dependent plasticity as the thalamic sensitive period. Visual deprivation before or after this period does not elicit similar changes in retinogeniculate connectivity. In the prior funding period, we showed that enhanced visual experience during the thalamic sensitive period can also trigger plasticity. Select exposure to a feature, referred to as select experience rearing (SER), can shift the population representation for that feature in dLGN. Moreover, these circuit changes are long-lasting, even if mice subjected to SER are subsequently re-exposed to normal vision. Our results support the idea that changes in retinogeniculate connectivity underlie SER plasticity and demonstrate that visual experience is not just permissive for plasticity but can instruct long-term changes in the thalamic circuits. In this current proposal, we turn our attention to the mature thalamus, asking whether plasticity also exists in the adult. Our preliminary studies suggest that there is plasticity in adult mice, however, unlike the developing brain, these changes do not persist. Here we propose to identify mechanisms that distinguish the transient nature of adult plasticity when compared to long-lasting changes that can occur during development. We will use a combination of tools including longitudinal in vivo two photon imaging of response preferences of thalamocortical neurons, in vivo single unit dLGN recordings, in vitro dLGN slice recordings and chemogenetics to characterize adult SER plasticity. We will also take advantage of mouse genetics, immunohistochemistry and 3-dimensional EM reconstruction to test the hypothesis that with age, glial ensheathment of retinal boutons in dLGN restricts rewiring of retinogeniculate connections, thus contributing to the difference between developmental and adult plasticity.