Journal
JOURNAL OF NEUROSCIENCE
Volume 36, Issue 25, Pages 6778-6791Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4092-15.2016
Keywords
hippocampus; integrin-Arg signaling; maturation; NMDA receptor; synaptic plasticity; synaptic stability
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Funding
- American Heart Association Postdoctoral Fellowship Grant [16POST27250302]
- National Institutes of Health [R01-NS-089662-01, R21-NS-089439-01, R01-MH-099045-03, F31-MH-105043-01, T32-GM-7223-39]
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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.
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