LRRTM1 underlies synaptic convergence in visual thalamus.

Aboozar Monavarfeshani,Jianmin Su,Kenya Swilling,Kaiwen Su,Alicia Kerr,Gail Stanton,Jonathan Van Name,Natalie A Huebschman,William A Mills,Michael A Fox

doi:10.7554/elife.33498

Abstract

It has long been thought that the mammalian visual system is organized into parallel pathways, with incoming visual signals being parsed in the retina based on feature (e.g. color, contrast and motion) and then transmitted to the brain in unmixed, feature-specific channels. To faithfully convey feature-specific information from retina to cortex, thalamic relay cells must receive inputs from only a small number of functionally similar retinal ganglion cells. However, recent studies challenged this by revealing substantial levels of retinal convergence onto relay cells. Here, we sought to identify mechanisms responsible for the assembly of such convergence. Using an unbiased transcriptomics approach and targeted mutant mice, we discovered a critical role for the synaptic adhesion molecule Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1) in the emergence of retinothalamic convergence. Importantly, LRRTM1 mutant mice display impairment in visual behaviors, suggesting a functional role of retinothalamic convergence in vision.

Highlights

Over thirty classes of functionally and morphologically distinct retinal ganglion cells (RGCs) exist in mammals, each responsible for conveying different features of the visual world and each with unique projections to retinorecipient nuclei within the brain (Sanes and Masland, 2015; Martersteck et al, 2017; Baden et al, 2016)
The recent development of transgenic tools to label these classes of RGCs has revealed that their inputs are segregated into distinct classspecific sublamina within visual thalamus (Huberman et al, 2008; Monavarfeshani et al, 2017; Huberman et al, 2009; Kay et al, 2011; Kim et al, 2008, 2010; Hong and Chen, 2011), supporting the longstanding belief that different features of the visual field are transmitted through the subcortical visual system in parallel, unmixed anatomical channels (Dhande et al, 2015; CruzMartın et al, 2014)
We discovered that relay cells in dLGN express Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1), a known inducer of excitatory synaptogenesis (Linhoff et al, 2009; de Wit et al, 2009)

Summary

Introduction

Over thirty classes of functionally and morphologically distinct retinal ganglion cells (RGCs) exist in mammals, each responsible for conveying different features of the visual world and each with unique projections to retinorecipient nuclei within the brain (Sanes and Masland, 2015; Martersteck et al, 2017; Baden et al, 2016). Is there a high level of retinogeniculate (RG) convergence in mice, but some relay cells receive input from functionally distinct classes of RGCs (Rompani et al, 2017) raising new questions about the role of thalamus in processing visual information before it reaches visual cortex Part of this newly appreciated retinal convergence stems from a set of unique RG synapses (termed complex RG synapses) that contain numerous retinal axons whose terminals aggregate on shared regions of relay cell dendrites (Morgan et al, 2016; Hammer et al, 2015; Lund and Cunningham, 1972). These results identify a novel mechanism underlying the establishment of retinal convergence in visual thalamus, and importantly provide the first insight into the functional significance of complex RG synapses (and, possibly, retinal convergence) in vision

Results

Materials and methods

Funding Funder National Eye Institute