Role for Visual Experience in the Development of Direction-Selective Circuits

Abstract

SUMMARYVisually-guided behavior can depend critically on detecting the direction of object movement. This computation is first performed in the retina where direction is encoded by direction-selective ganglion cells (DSGCs) that respond strongly to an object moving in the preferred direction and weakly to an object moving in the opposite, or null, direction (reviewed in [1]). These DSGCs come in multiple types that are classified based on their morphologies, response properties and targets in the brain. This study focuses on two types -ON and ON-OFF DSGCs. Though animals can sense motion in all directions, the preferred directions of DSGCs in adult retina cluster along distinct directions that we refer to as the cardinal axes. ON DSGCs have three cardinal axestemporal, ventral and dorsonasal -while ON-OFF DSGCs have four -nasal, temporal, dorsal, and ventral. How these preferred directions emerge during development is still not understood. Several studies have demonstrated that ON [2] and ON-OFF DSGCs are well tuned at eye-opening, and even a few days prior to eye-opening, in rabbits [3], rats [4] and mice [5][6][7][8], suggesting that visual experience is not required to produce direction selective tuning. However, here we show that at eye-opening the preferred directions of both ON and ON-OFF DSGCs are diffusely distributed and that visual deprivation prevents the preferred directions from clustering along the cardinal axes. Our findings indicate a critical role for visual experience in shaping responses in the retina. HHS Public Access RESULTS Clustering of DSGC preferred directions along cardinal axes after eye-opening requires visual experienceWe used two-photon calcium imaging to study the development of DSGC populations in mouse retina. This imaging technique has proven to be quite powerful in characterizing the receptive field properties of retinal ganglion cells [9][10][11][12]. We loaded retinas of WT mice near eye-opening (P13-P14) and in adulthood (>P30) with the calcium dye Oregon green 488 BAPTA-1 hexapotassium salt (OGB-1) via electroporation, thus uniformly labeling the ganglion cell layer ( Figure 1A; see Supplemental Information). Ventral portions of the retina were stimulated with light centered at 385 nm to maximally activate UV-cones [13,14] while minimizing cross talk with the imaging detectors ( Figure S1). This approach allowed us to record from all DSGC subtypes within a single field of view (~40000 μm 2 ).To identify DSGCs, we first used full field UV-light flashes to classify cells as ON, OFF or ON-OFF retinal ganglion cells (RGCs) ( Figure S1; Table S1). We found that around 80% of the cells in the ganglion cell layer of young and adult retinas responded to light flashes with changes in fluorescence (Table S1), similar to the RGC percentages reported in previous studies [9,11,12]. In addition, over development we observed a decrease in the percentage of ON-OFF RGCs (28.03% at P13-14 to 20.84% in adult) (Table S1) [15].Second, we used light bars on a dark background drifting in 8 dir...

Direction selectivity in retinal bipolar cell axon terminals

“…What kind of mechanisms could establish the tuned glutamate releases that are aligned with all four cardinal directions even though ACh releases from starburst cells at individual synaptic sites represent more than the cardinal directions (Figure S4M)? Notably, activity-dependent (Bos et al, 2016) and protocadherin-dependent (Kostadinov and Sanes, 2015) mechanisms have been suggested to facilitate the clustering of preferred directions of DSGCs. Similar molecular and/or cellular mechanisms that restrict the angle of inputs may be at work selectively at tuned boutons in the bipolar cell.…”

Development of Natural Scene Representation in Primary Visual Cortex Requires Early Postnatal Experience

“…50 The development of selectivity for direction of motion is highly dependent on visual experience, observed at the cortical level [51][52][53][54] as well as at upstream stages, such as the retina. 55 Furthermore, the representation of direction of motion might be more unstable on a neuronby-neuron basis within the V1 compared with the representation of orientation. 56,57 The use of static stimuli allowed us to demonstrate that experience-mediated improvements in scene representation are observed for stimuli that do not contain motion.…”

Development of natural scene representation in primary visual cortex requires early postnatal experience

“…It is becoming increasingly apparent that the mouse visual system can respond to high spatial frequencies in moving stimuli [34], consistent with natural visual behavior [50]. The development of selectivity for direction of motion is highly dependent on visual experience, observed at the cortical level [51][52][53][54] as well as at upstream stages such as the retina [55]. Furthermore, the representation of direction of motion may be more unstable on a neuron-byneuron basis within V1 compared to the representation of orientation [56,57].…”