Neural extracellular matrix regulates visual sensory motor integration

Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components brevican, neurocan, tenascin-C and tenascin-R in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing in vivo. Remarkably, impaired visual motion processing was accompanied by a developmental loss of cholinergic direction-selective starburst amacrine cells. Additionally, we noted imbalance of inhibitory and excitatory synaptic signaling in the quadruple knockout retina. Collectively, the study offers novel insights into the functional importance of four key extracellular matrix proteins for retinal function, visual motion processing and synaptic integrity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=73 SRC="FIGDIR/small/537074v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@eec571org.highwire.dtl.DTLVardef@1e4b282org.highwire.dtl.DTLVardef@18398a7org.highwire.dtl.DTLVardef@9b113b_HPS_FORMAT_FIGEXP M_FIG C_FIG In briefIn their study, Reinhard et al. show that the combined loss of the extracellular matrix components brevican, neurocan, tenascin-C and tenascin-R in quadruple knockout mice leads to retinal dysfunction, diminished visual motion processing, developmental loss of cholinergic direction-selective starburst amacrine cells and imbalance of inhibitory and excitatory synaptic integrity. HighlightsO_LICombined loss of the four extracellular matrix molecules brevican, neurocan, tenascin-C and tenascin-R causes retinal dysfunction C_LIO_LIImpaired visual motion processing in quadruple, tenascin-C and tenascin-R knockout mice C_LIO_LILoss of cholinergic direction-selective starburst amacrine cells in the quadruple knockout retina C_LIO_LIThe matrisome influences inhibitory and excitatory synaptic balance C_LI