UC San Diego

The establishment and stabilization of proper synaptic connections is a vital step in the maturation of cortical circuits. The prevention of these processes can lead to downstream developmental delays and unstable connections in the adult. We show that astrocyte expressed glypican 5 (Gpc5) is necessary for the refinement and strengthening of thalamocortical synapses in the mouse primary visual cortex binocular zone (V1b) during the critical period. Using electron microscopy, we show that in the absence of Gpc5, thalamocortical synapses show distinct structural immaturity, including smaller boutons and weaker synapses during the critical period. This structural immaturity is accompanied by a delay in the developmental incorporation of GluA2-containing calcium impermeable AMPARs at intracortical synapses, as observed using immunohistochemistry. Upon reaching adulthood, mice lacking astrocytic Gpc5 demonstrate intact synaptic composition but exhibit increased levels of ocular dominance plasticity, potentially as a result of destabilized thalamocortical synapses. The work in this thesis suggests that astrocytic Gpc5 is necessary for the stabilization of thalamocortical terminals during development and in the adult.