Astrocytic Factors Controlling Synaptogenesis: A Team Play

Abstract

Astrocytes are essential players in brain circuit development and homeostasis, controlling many aspects of synapse formation, function, plasticity and elimination both during development and adulthood. Accordingly, alterations in astrocyte morphogenesis and physiology may severely affect proper brain development, causing neurological or neuropsychiatric conditions. Recent findings revealed a huge astrocyte heterogeneity among different brain areas, which is likely at the foundation of the different synaptogenic potential of these cells in selected brain regions. This review highlights recent findings on novel mechanisms that regulate astrocyte-mediated synaptogenesis during development, and the control of synapse number in the critical period or upon synaptic plasticity.

Keywords: astrocyte diversity; astrocyte factors; synaptic plasticity; synaptic pruning; synaptogenesis.

Figure 1

TSP1 and PTX3 cooperate to promote early formation of functional excitatory synapses. TSP1 binds to the α2δ1 receptor on the presynaptic terminals stimulating an increase in structurally normal but silent synapses, and to the α2δ1 receptor at the postsynaptic site, activating Rac1 and stimulating actin remodeling to promote spinogenesis. PTX3 promotes the functional maturation of these synapses by recruiting AMPA receptors at the synapse.

Figure 2

Hevin and SPARC. Astrocyte-secreted Hevin bridges presynaptic neurexin and postsynaptic neuroligin to favor the recruitment of PSD95 and NMDAR subunits at the synapse. SPARC on the contrary antagonizes Hevin’s effect with a still unknown mechanism.

Figure 3

Glypican 4 and Neuronal Pentraxin 1. Astrocyte-derived Glypican 4 induces NP1 release from neurons through the PTPRδ receptor. NP1 stimulates AMPA receptors’ clustering on the postsynaptic terminal, making the synapse functional.