Refinement of spatial receptive fields in the developing mouse LGN is coordinated with excitatory and inhibitory remodeling

36 Receptive field properties of individual visual neurons are dictated by the precise patterns 37 of synaptic connections they receive, including the arrangement of inputs in visual space 38 and features such as polarity (On versus Off). The inputs from retina to the lateral 39 geniculate nucleus (LGN) in the mouse undergo significant refinement over 40 development, however it is unknown how this corresponds to the establishment of 41 functional visual response properties. Here we conducted in vivo and in vitro recordings 42 in mouse LGN, beginning just after natural eye opening to determine how receptive fields 43 develop as excitatory and feed-forward inhibitory retinal afferents refine. Experiments 44 used both male and female subjects. For in vivo assessment of receptive fields, we 45 performed multisite extracellular recordings in awake mice. Spatial receptive fields were 46 over twice as large at eye-opening as in adults, and then reduced in size over the 47 subsequent week. This topographic refinement was accompanied by other spatial changes 48 such as a decrease in spot size preference and an increase in surround suppression. 49 Notably, the degree of specificity in terms of On/Off and sustained/transient responses 50 appeared to be established already at eye opening and did not change. During the same 51 time, in vitro recordings of the synaptic responses evoked by optic tract stimulation 52 revealed a pairing of decreased excitatory and increased feed-forward inhibitory 53 convergence, providing a potential mechanism to explain the spatial receptive field 54 refinement. 55 In this study we investigated the refinement of both excitatory and feed-forward 88 inhibitory inputs onto dLGN relay cells to determine whether there is coordination with 89 RF development. We measured receptive fields using the spike-triggered average 90 estimate of spatial structure, and discovered significant refinement during the first week 91 after eye opening. This included a significant decrease in RF size and stimulus size 92 preference. We were also able to determine whether refinement occurs by cell type 93 (ON/OFF, transient/sustained) or if it is topographic. To disambiguate the effects of 94 refinement of retinal inputs from changes in retinal RFs during development, we mapped 95 RGC RFs by recording from axons in the optic nerve in vivo. Lastly, to further 96 understand the underlying circuitry that accompany these changes we recorded excitatory 97 and inhibitory synaptic responses in vitro by applying electrical stimulation to the optic 98 tract in an acute thalamic slice preparation that preserves retinal afferents and intrinsic 99 inhibitory circuitry within LGN. The in vitro measurements showing a pairing of 100 decreased excitatory convergence with increased inhibitory convergence provide a 101 potential mechanism that shapes adult-like receptive field structure in dLGN. Here we link the remodeling of retinogeniculate connections with developmental changes in dLGN receptive field properties. Our in vivo recordings revealed two important changes in receptive field