RT Journal Article
SR Electronic
T1 A new organotypic model of synaptic competition reveals activity-dependent localization of C1q
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 118646
DO 10.1101/118646
A1 Ryuta Koyama
A1 Yuwen Wu
A1 Allison R. Bialas
A1 Andrew Thompson
A1 Christina A. Welsh
A1 Arnaud Frouin
A1 Chinfei Chen
A1 Beth Stevens
YR 2017
UL http://biorxiv.org/content/early/2017/03/20/118646.abstract
AB Immature neural circuits undergo synaptic refinement, in which activity-dependent competition between synapses results in pruning of inappropriate connections and maintenance of appropriate ones. A longstanding question is how neuronal activity eliminates specific synapses based on their strength. The technical challenges of in vivo studies have made it difficult to identify a molecular link between decreased activity and synapse elimination. We developed an organotypic coculture model of the mouse retinogeniculate system that facilitates real-time imaging and elucidation of molecular mechanisms underlying the removal of less active synapses during synaptic competition. Using this model we show for the first time that complement component C1q is necessary for activity-dependent synaptic competition and preferentially localizes to less active, competing presynaptic inputs. In conjunction with classic in vivo and ex vivo models, this coculture model is a new tool to reveal molecular pathways underlying CNS circuit refinement.