A Role for Corticothalamic Feedback in Developmental Refinement at the Retinogeniculate Synapse.
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CitationThompson, Andrew. 2016. A Role for Corticothalamic Feedback in Developmental Refinement at the Retinogeniculate Synapse.. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractThe primary image-forming pathway in the mammalian visual system relays information from photoreceptors in the retina through the dorsolateral geniculate nucleus (dLGN) in the thalamus to primary visual cortex (V1). In mice, the projection from retinal ganglion cells to thalamic relay neurons in the dLGN, the retinogeniculate synapse, undergoes a prolonged period of synaptic remodeling in the first weeks of postnatal development, pruning down from many retinal inputs per postsynaptic cell to few. Relay neurons in the dLGN also receive extensive monosynaptic excitatory and disynaptic inhibitory feedback from layer 6 of V1, which has been demonstrated to influence visual processing in the mature circuit. However, the contribution of these corticothalamic projections to developmental synaptic refinement in the thalamus has not been explored.
Here we demonstrate, using pharmacological and chemogenetic perturbations, that retinothalamic development is highly sensitive to cortical feedback during a recently defined thalamic critical period. Broad inhibition of activity in V1 via stereotactic injection of the GABA(A) receptor agonist muscimol led to destabilization of the retinothalamic circuit, with numerous weak retinal inputs accruing onto relay neurons between postnatal day 20 (P20) and P27, similar to a phenotype observed in response to visual deprivation during this time period. Selective suppression of feedback from the corticothalamic-projecting pyramidal cells in layer 6 of V1 with the inhibitory Designer Receptor Exclusively Activated by Designer Drug (DREADD) HM4Di during this time frame also disrupted refinement of the retinogeniculate input, with additional strong retinal inputs innervating each relay neuron. We then tested whether subcortical development responds to a loss of cortical feedback, or simply to a change in feedback, and found that increasing L6 output with the excitatory DREADD, HM3Dq, also effected rewiring of the retinogeniculate input.
Developmental refinement at the retinogeniculate synapse undergoes a critical period from P20 to P30, wherein visual deprivation induces the recruitment of additional retinal afferents. We found that manipulating cortical feedback after this window did not have any effect on retinogeniculate wiring, suggesting that proper feedback from cortex is required, along with vision, specifically during the critical period to stabilize the connections from retina to thalamus.
Our results demonstrate, for the first time, regulation of feedforward development of a subcortical sensory pathway by feedback from cortex. Thus, primary sensory pathways may develop, at least in part, through the concomitant rewiring of subcortical and cortical circuits in response to sensory experience.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:33493598
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