Disruption of Coordinated Presynaptic and Postsynaptic Maturation Underlies the Defects in Hippocampal Synapse Stability and Plasticity in Abl2/Arg-Deficient Mice

作者：Xiao Xiao; Levy Aaron D; Rosenberg Brian J; Higley Michael J; Koleske Anthony J

来源：Journal of Neuroscience, 2016, 36(25): 6778-6791.

DOI：10.1523/JNEUROSCI.4092-15.2016

• hippocampus
• integrin-Arg signaling
• maturation
• NMDA receptor
• synaptic plasticity
• synaptic stability

Immature glutamatergic synapses in cultured neurons contain high-release probability (P-r) presynaptic sites coupled to postsynaptic sites bearing GluN2B-containing NMDA receptors (NMDARs), which mature into low-P-r, GluN2B-deficient synapses. Whether this coordinated maturation of high-P-r, GluN2B(+) synapses to low-P-r, GluN2B-deficient synapses actually occurs in vivo, and if so, what factors regulate it and what role it might play in long-term synapse function and plasticity are unknown. We report that loss of the integrinregulated Abl2/Arg kinase in vivo yields a subpopulation of "immature" high-P-r, GluN2B(+) hippocampal synapses that are maintained throughout late postnatal development and early adulthood. These high-P-r, GluN2B(+) synapses are evident in arg(-/-) animals as early as postnatal day 21 (P21), a time that precedes any observable defects in synapse or dendritic spine number or structure in arg(-/-) mice. Using focal glutamate uncaging at individual synapses, we find only a subpopulation of arg(-/-) spines exhibits increased GluN2B-mediated responses at P21. As arg(-/-) mice age, these synapses increase in proportion, and their associated spines enlarge. These changes coincide with an overall loss of spines and synapses in the Arg-deficient mice. We also demonstrate that, although LTP and LTD are normal in P21 arg(-/-) slices, both forms of plasticity are significantly altered by P42. These data demonstrate that the integrin-regulated Arg kinase coordinates the maturation of presynaptic and postsynaptic compartments in a subset of hippocampal synapses in vivo, and this coordination is critical for NMDAR-dependent long-term synaptic stability and plasticity.

• 出版日期2016-6-22