Architecture and Activity-Mediated Refinement of Axonal Projections from a Mosaic of Genetically Identified Retinal Ganglion Cells

Department of Neurobiology, Fairchild Science Building D235, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
Neuron (Impact Factor: 15.05). 09/2008; 59(3):425-38. DOI: 10.1016/j.neuron.2008.07.018
Source: PubMed


Our understanding of how mammalian sensory circuits are organized and develop has long been hindered by the lack of genetic markers of neurons with discrete functions. Here, we report a transgenic mouse selectively expressing GFP in a complete mosaic of transient OFF-alpha retinal ganglion cells (tOFF-alphaRGCs). This enabled us to relate the mosaic spacing, dendritic anatomy, and electrophysiology of these RGCs to their complete map of projections in the brain. We find that tOFF-alphaRGCs project exclusively to the superior colliculus (SC) and dorsal lateral geniculate nucleus and are restricted to a specific laminar depth within each of these targets. The axons of tOFF-alphaRGC are also organized into columns in the SC. Both laminar and columnar specificity develop through axon refinement. Disruption of cholinergic retinal waves prevents the emergence of columnar- but not laminar-specific tOFF-alphaRGC connections. Our findings reveal that in a genetically identified sensory map, spontaneous activity promotes synaptic specificity by segregating axons arising from RGCs of the same subtype.

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    • "RGC axons enter the tectum at one of four sublaminae and remain in those layers to find and refine their topographic connections (Robles et al., 2013). The lamina targeted by each RGC depends on the RGC subtype and intrinsic properties, although most RGCs innervate superficial laminae within the neuropil (Yamagata and Sanes, 1995; Xiao et al., 2005; Huberman et al., 2008, 2009; Gabriel et al., 2012; Nikolaou et al., 2012; Antinucci et al., 2013). The secreted protein Slit1, expressed in a highsuperficial to low-deep gradient, signals to Robo2 receptors on the RGC axons to guide axons into the correct lamina (Xiao et al., 2011). "
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    ABSTRACT: The zebrafish retinotectal projection provides an attractive model system for studying many aspects of topographic map formation and maintenance. Visual connections initially start to form between three and five days post fertilization, and remain plastic throughout the life of the fish. Zebrafish are easily manipulated surgically, genetically and chemically, and a variety of molecular tools exist to enable visualization and control of various aspects of map development. Here we review zebrafish retinotectal map formation, focusing particularly on the detailed structure and dynamics of the connections, the molecules that are important in map creation, and how activity regulates the maintenance of the map. This article is protected by copyright. All rights reserved. Copyright © 2014 Wiley Periodicals, Inc., a Wiley company.
    Full-text · Article · Jun 2015 · Developmental Neurobiology
    • "urons that receive ON – OFF DSGC input in turn project specifically to superficial layers of the primary visual cortex ( V1 ) to deliver direction - selective ( and orientation - selective ) information to cells / processes that reside in superficial V1 layers . In contrast , non - direction - tuned RGCs ( blue ) project to the dLGN ' ' core ' ' ( Huberman et al . 2008 , 2009 ) . Neurons in the core project to deeper layers of V1 , thereby establishing a parallel circuit ( see Cruz - Mart ın et al . 2014 for details ) . Wernet et al . 2576 GENES & DEVELOPMENT"
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    ABSTRACT: The visual system is a powerful model for probing the development, connectivity, and function of neural circuits. Two genetically tractable species, mice and flies, are together providing a great deal of understanding of these processes. Current efforts focus on integrating knowledge gained from three cross-fostering fields of research: (1) understanding how the fates of different cell types are specified during development, (2) revealing the synaptic connections between identified cell types ("connectomics") by high-resolution three-dimensional circuit anatomy, and (3) causal testing of how identified circuit elements contribute to visual perception and behavior. Here we discuss representative examples from fly and mouse models to illustrate the ongoing success of this tripartite strategy, focusing on the ways it is enhancing our understanding of visual processing and other sensory systems. © 2014 Wernet et al.; Published by Cold Spring Harbor Laboratory Press.
    No preview · Article · Dec 2014 · Genes & Development
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    • "A-type ON sustained, M4, M5 (Margolis & Detwiler, 2007; van Wyk et al. 2009; Estevez et al. 2012; Bleckert et al. 2014); inner α (Tagawa et al. 1999); ON Y-cell (Borghuis et al. 2013) Melanopsin M1 0–20% G19 Opn4Cre /+ ; Z/EG (Ecker et al. 2010); Opn4-EGFP (Schmidt et al. 2008) Melanopsin M2 80–100% — Opn4Cre /+ ; Z/EG (Ecker et al. 2010); Opn4-EGFP (Schmidt et al. 2008) Melanopsin M3 0–20%, 80–100% — Opn4-EGFP (Schmidt et al. 2008) JamB 0–30% G15 JamB-Cre-ER (Kim et al. 2008) W7a 0–20%, 30–40% — TYW7 (Kim et al. 2010); A-type OFF sustained (Margolis & Detwiler, 2007; van Wyk et al. 2009; Bleckert et al. 2014); outer δ (Tagawa et al. 1999) W7b 30–40% — TYW7 (Kim et al. 2010); A-type OFF transient (Margolis & Detwiler, 2007; van Wyk et al. 2009); CB2-GFP (Huberman et al. 2008; but see S ¨ umbül et al. 2014); outer α (Tagawa et al. 1999); OFF Y-cell (Borghuis et al. 2013); PV-5 (M ¨ unch et al. 2009) ON DS (Hoxd10) 55–70%, 15–20% — ON direction selective, Hoxd10-GFP (Dhande et al. 2013); SPIG1 (Yonehara et al. 2008) Classification of ganglion cell types (first column). Ganglion cell dendritic stratification levels in the inner plexiform layer where 0 indicates the outer border and 100 indicates the inner border (second column). "
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    Preview · Article · Aug 2014 · The Journal of Physiology
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