| First Author | Crawford DC | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14436 | PubMed ID | 28186166 |
| Mgi Jnum | J:244763 | Mgi Id | MGI:5913542 |
| Doi | 10.1038/ncomms14436 | Citation | Crawford DC, et al. (2017) Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy. Nat Commun 8:14436 |
| abstractText | Recent studies suggest that stimulus-evoked and spontaneous neurotransmitter release processes are mechanistically distinct. Here we targeted the non-canonical synaptic vesicle SNAREs Vps10p-tail-interactor-1a (vti1a) and vesicle-associated membrane protein 7 (VAMP7) to specifically inhibit spontaneous release events and probe whether these events signal independently of evoked release to the postsynaptic neuron. We found that loss of vti1a and VAMP7 impairs spontaneous high-frequency glutamate release and augments unitary event amplitudes by reducing postsynaptic eukaryotic elongation factor 2 kinase (eEF2K) activity subsequent to the reduction in N-methyl-D-aspartate receptor (NMDAR) activity. Presynaptic, but not postsynaptic, loss of vti1a and VAMP7 occludes NMDAR antagonist-induced synaptic potentiation in an intact circuit, confirming the role of these vesicular SNAREs in setting synaptic strength. Collectively, these results demonstrate that spontaneous neurotransmission signals independently of stimulus-evoked release and highlight its role as a key regulator of postsynaptic efficacy. |
