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

Abstract

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.

Morphologically Distinct Classes of Relay Cells Exhibit Regional Preferences in the Dorsal Lateral Geniculate Nucleus of the Mouse

“…These RGC types also terminate in ventromedial regions of dLGN, an area in which some W-like cells were located. Additionally, we found that X-like cells that showed perhaps the strongest regional preference residing almost exclusively in the ventroposterior region of dLGN just dorsal to IGL seem to represent just a small portion of much larger terminal domains for several indentified RGC types that vary both in morphology and receptive field structure (Hattar et al, 2006;Huberman et al, 2008Huberman et al, , 2009Kim et al, 2008Kim et al, , 2010Badea et al, 2009;Siegert et al, 2009;Ecker et al, 2010;Kay et al, 2011). Indeed, such overlap between RGC projections and the spatial preferences of dLGN cells is to be expected given the wide diversity of RGC types (Masland, 2001).…”

“…For example, we found that Y-like cells occupy a central core in dLGN, a region that serves as the primary terminal domain for transient Off-␣-cells and a group of On/Off direction-selective cells that responds to posterior motion (Huberman et al, 2008;Kim et al, 2010. These RGC types also terminate in ventromedial regions of dLGN, an area in which some W-like cells were located.…”

“…For example, in the retina, several classes of retinal ganglion cells (RGCs) have been identified, and many of these seem to comprise separate channels that have distinct molecular, morphological, and functional features, as well as unique patterns of connectivity and central projections (Hattar et al, 2006;Huberman et al, 2008Huberman et al, , 2009Kim et al, 2008Kim et al, , 2010Yonehara et al, 2008;Siegert et al, 2009;Ecker et al, 2010;Hong et al, 2011;Kay et al, 2011;RivlinEtzion et al, 2011). Nonetheless, what remains unexplored in the mouse is whether these separate retinal channels are preserved and recapitulated in a parallel manner onto recipient cells in central target structures.…”

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

“…2B, a single oligodendrocyte outlined by NG2 expression shows overlapping staining for Contactin on the cell body and on proximal but not distal processes. At P10, Contactin was undetectable on optic axons that by this time point had innervated their targets (20,21). At P16, a dramatic change in pattern occurred, with prominent Contactin staining now delineating parallel running structures resembling myelin membranes.…”

In vivo imaging of the zebrafish retinotectal map

“…RGC axons enter the tectum at one of four sublaminae and remain in those layers to find and refine their topographic connections [267]. The lamina targeted by each RGC depends on the RGC subtype and intrinsic properties, although most RGCs innervate superficial laminae within the neuropil [5,90,141,142,238,362,366]. The secreted protein Slit1, expressed in a high-superficial to low-deep gradient, signals to Robo2 receptors on the RGC axons to guide axons into the correct lamina [363].…”