Optic flow instructs retinotopic map formation through a spatial to temporal to spatial transformation of visual information

Abstract

Retinotopic maps are plastic in response to changes in sensory input; however, the experience-dependent instructive cues that organize retinotopy are unclear. In animals with forward-directed locomotion, the predominant anterior to posterior optic flow activates retinal ganglion cells in a stereotyped temporal to nasal sequence. Here we imaged retinotectal axon arbor location and structural plasticity to assess map refinement in vivo while exposing Xenopus tadpoles to visual stimuli. We show that the temporal sequence of retinal activity driven by natural optic flow organizes retinotopy by regulating axon arbor branch dynamics, whereas the opposite sequence of retinal activity prevents map refinement. Our study demonstrates that a spatial to temporal to spatial transformation of visual information controls experience-dependent topographic map plasticity. This organizational principle is likely to apply to other sensory modalities and projections in the brain.temporal code | topographic map | activity-dependent plasticity | STDP | visual system I n the visual system, the sensory world is mapped onto the planar array of retinal ganglion cells (RGCs), and this representation of the visual world is then conveyed to the CNS via the spatial distribution of retinal axons in the target area. It is widely accepted that molecular cues guide retinal axons to approximate regions along the rostrocaudal axis of the target and that activitydependent mechanisms refine this crude map (1-3). Moreover, retinotopic maps show experience-dependent plasticity throughout life, allowing them to accommodate changes in the sensory periphery as well as the brain. Current models of activity-dependent mechanisms of topographic map plasticity are based on coactivity rules (4-7), however information in natural scenes may be encoded in additional temporal properties of neuronal firing other than coactivity (8-11). For instance, temporal features of RGC spiking have been shown to encode information about the visual stimuli (12). Movement of objects through the visual field activates RGCs in a temporal sequence, which corresponds to a progression of spatial locations of the object in the visual scene. This raises the possibility that the temporal sequence of RGC activity might encode spatial information that can be used to organize retinotopic maps.A candidate visual input that shapes retinotopy is optic flow. In most forward-moving animals, the direction of optic flow is biased from anterior to posterior (A→P). For instance, tadpoles always swim forward, and the predominant visual stimulus they experience is A→P motion within the visual scene. This generates an overall correlation between the sequential order of RGC activity from temporal to nasal retina and the retinotopic distribution of axon projections along the rostrocaudal axis of the tectal target (13). However, whether or how the relative sequence of activity induced by optic flow organizes retinotopy is unclear.We tested whether the spatial arrangement of sensory afferents in the retino...

Rules for Shaping Neural Connections in the Developing Brain

“…Retinal waves in zebrafish also stereotypically originate from the temporal retina (Zhang et al, 2016). In tadpoles, it has been shown directly that visual stimulation which includes optic flow in this more natural direction is far more effective at refining the retinotopic projection of RGCs than an identical amount of stimulation oriented in the opposite direction (Hiramoto and Cline, 2014). The mechanisms generating waves in the mammalian retina differ over development: embryonic type I waves depend on gap junctions; type II waves are initiated by starburst amacrine cells and spread through activation of nicotinic acetylcholine receptors; and type III waves utilize glutamate (Feller et al, 1996; Bansal et al, 2000; Torborg et al, 2005; see reviews in this special topic issue by Arroyo and Feller (2016) and Kerschensteiner (2016).…”

An NMDA receptor-dependent mechanism for subcellular segregation of sensory inputs in the tadpole optic tectum

“…Conversely, if there is a low degree of correlation, it will be eliminated (Ruthazer et al, 2003; Munz et al, 2014). This concept of correlated inputs wiring to common regions of dendrite is supported by the finding that RGC inputs form a subcellular map across individual tectal neurons such that near-neighbor RGC inputs, which would display a high degree of correlated firing, target to near neighbor region of dendrite (Bollmann and Engert, 2009), and further the super-correlated pattern of RGC firing created by optic flow across the retina has been shown to enhance refinement (Hiramoto and Cline, 2014). Thus, across a common dendrite, any HB axon that is in the vicinity of RGC axons would not be able to form stable synapses in that area because the firing patterns of HB inputs are not correlated with RGC patterns.…”

Direct intertectal inputs are an integral component of the bilateral sensorimotor circuit for behavior in Xenopus tadpoles

“…Monocular visual experience protocol. Animals were exposed to monocular visual experience before electrophysiology and behavior experiments by being presented with visual stimuli, as described previously (Hiramoto and Cline 2014). Stage 47 tadpoles were anesthetized in 0.02% MS-222 and then placed in a transparent chamber containing a layer of Sylgard (catalog no, 24236-10; Electron Microscopy Science).…”

“…The entire preparation was submerged in fresh 1ϫ Steinberg's solution, and the tadpole was allowed to recover from anesthesia. The chamber was placed 15 mm from a liquid crystal display (LCD) screen, which showed pseudorandomly moving bar stimuli modified from Hiramoto and Cline (2014). The moving bars consisted of alternating 9-mm-wide white bars and 27-mm-wide black bars moving at 78 mm/s.…”