Increase in syntaxin 1B and glutamate release in mossy fibre terminals following induction of LTP in the dentate gyrus: a candidate molecular mechanism underlying transsynaptic plasticity

Abstract

A growing body of evidence suggests that modulation of certain proteins of the exocytotic machinery is, in part, involved in the biochemical changes that underlie long-term synaptic plasticity. We have previously shown that the induction of long-term potentiation (LTP) at perforant path to dentate granule cell synapses in the rat hippocampus induces changes in the mRNA levels of syntaxin 1B and synapsin I, known to be involved in neurotransmitter release. Immunohistochemical staining suggested that concomitant changes in these proteins occurred at mossy fibre synapses, downstream of those synapses at which LTP was induced, leading us to postulate that such a mechanism might underlie a form of transsynaptic plasticity. Here we have used a specific mossy-fibre synaptosome preparation to quantify levels of proteins and measure, using a chemiluminescent glutamate assay, depolarization-induced glutamate release from these synaptosomes after induction of LTP in the dentate gyrus in vivo. We show that 5 h after the induction of LTP, there is an increase in the protein levels of syntaxin 1B and, although to a lesser extent, the synapsins I and II, associated with an increase in depolarization-induced release of glutamate within these terminals. Increases in both the protein levels and glutamate release were not observed when dentate gyrus LTP was blocked by an NMDA receptor antagonist. From these results we propose a molecular mechanism for the propagation of synaptic plasticity through hippocampal circuits.

Stable Mossy Fiber Long-Term Potentiation Requires Calcium Influx at the Granule Cell Soma, Protein Synthesis, and Microtubule-Dependent Axonal Transport

“…A number of studies have demonstrated that the abundance of presynaptic proteins can be modified by activity. For instance, LTP induction in the dentate gyrus in vivo causes upregulation of syntaxin1b and synapsin I mRNA and protein in the MF pathway, and an increase of glutamate release from MF terminals (Hicks et al, 1997;Helme-Guizon et al, 1998). In addition, an increase in synapsin, synaptotagmin, and synaptophysin levels has been observed in the dentate gyrus following perforant path LTP induction in vivo (Lynch et al, 1994).…”

P2X7 receptor activation downmodulates Na+-dependent high-affinity GABA and glutamate transport into rat brain cortex synaptosomes

“…Synaptosomes were isolated as previously described by Helme-Guizon et al (1998) and then modified by Bancila et al (2009). Briefly, the cerebral cortex was dissected out and gently homogenized in cold oxygenated (95% O 2 and 5% CO 2 ) Krebs solution (in mM: glucose 5.5, NaCl 136, KCl 3, MgCl 2 1.2, Na 2 HPO 4 1.2, NaHCO 3 16.2, CaCl 2 0.5, pH 7.40).…”

Vesicular Zinc Regulates the Ca2+Sensitivity of a Subpopulation of Presynaptic Vesicles at Hippocampal Mossy Fiber Terminals

“…The assay is based on a coupled reaction in which glutamate released from MFS produces nicotinamide adenine dinucleotide, which was monitored in "real-time" by a chemiluminescent reaction (Fosse et al, 1986;Helme-Guizon et al, 1998;Bancila et al, 2009) using a Packard Fusion microplate reader. MFS equivalent to 125 g (ϳ5 l) of total protein was resuspended to a final volume of 30 l in the Krebs' buffer.…”