, 2008a and Triplett et al., 2009). However, this topographic axon targeting precedes the major periods of synapse formation, functional maturation, and input refinement that coincide with the onset of environmental drive (Lu and Constantine-Paton, 2004). This “consolidation” phase of refinement

in the sSC is likely to involve both synaptic elaboration and elimination as individual retinal and cortical axons sort their terminals on postsynaptic cells. Little is known about this process or its cellular mechanisms, which allow precise refinement of converging projections. Entinostat cell line Simple Hebbian mechanisms are predicted to suppress the later-arriving cortical inputs unless their activity is closely synchronized with that of earlier synapses (Constantine-Paton et al., 1990). This has led us to the hypothesis that late arriving, broadly mapped,

inputs such as those from VC have specific adaptations to enable successful wiring. Here we control EO to precisely define the onset of pattern vision, and combine this with in vivo anterograde labeling of retinal CHIR 99021 and cortical afferents to sSC and anatomical reconstruction of cells expressing a genetically encoded eGFP in a population of collicular neurons located at the interface of the two projections. We follow changes in these neurons and the cortical input in age-matched animals with opened or closed eyelids using quantitative structural and whole-cell patch clamp analyses. These approaches identify structural and functional changes at synapses over the EO interval of identified sSC neurons, and highlight those changes specifically controlled by early visual experience. In vivo multiunit recording of spontaneous and visually evoked activity in sSC and VC layer 5 of intact awake pups are used to reveal the relative latencies of vision-driven activity in cortex and sSC. These data provide evidence for a spike-timing dependent mechanism

that underlies the successful stabilization of cortical synapses on sSC neurons with EO, very and the net synaptic loss observed when the eyes remain closed. In this study, we focus on a distinct population of sSC neurons with vertically distributed and predominantly dorsal dendrites (dorsally oriented vertical [DOV] neurons) lying within both retinal and cortical terminal zones. These cells were labeled early in eGFP mice and are also identifiable with IR-DIC optics using laminar position, somatic shape, and dendritic orientation (Tokunaga and Otani, 1976). Based on earlier work (Lu and Constantine-Paton, 2004, Philpot et al., 2001 and Yoshii et al., 2003), and the finding that normal levels of PSD-95 are required to produce NMDA receptor-dependent long-term potentiation and depression (Béïque and Andrade, 2003 and Migaud et al., 1998), we hypothesized that PSD-95 is crucial to rapid, EO-induced synaptic remodeling through its stabilization of synapses sensitive to the new stimuli. PSD-95 is highly expressed in DOV neurons and sSC synapses (see Figure S1 available online).