VAMP4 Maintains a Ca2+-Sensitive Pool of Spontaneously Recycling Synaptic Vesicles

• DOI: 10.1523/jneurosci.2386-19.2020
• Publication Date: 2020-06-12T21:45:29Z
• Authors: Pei-Yi Lin; Natali L. Chanaday; Patricia M. Horvath; Denise M.O. Ramirez; Lisa M. Monteggia; Ege T. Kavalali
• Keywords: SNARE complex; Synapsin; Kiss-and-run fusion

Spontaneous neurotransmitter release is a fundamental property of synapses in which filled vesicles their content independent presynaptic action potentials (APs). Despite seemingly random nature, these spontaneous fusion events can be regulated by Ca²⁺ signaling pathways. Here, we probed the mechanisms that maintain sensitivity formed between hippocampal neurons cultured from rats both sexes. In this setting, examined potential role vesicle-associated membrane protein 4 (VAMP4), vesicular soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) neurotransmission. Our results show VAMP4 required for Ca²⁺-dependent excitatory neurotransmission, with limited inhibitory Key residues regulate its retrieval as well functional clathrin-mediated vesicle trafficking were essential maintenance VAMP4-mediated release. Moreover, high-frequency stimulation (HFS) typically triggers asynchronous and plasma also augmentsCa²⁺-sensitive up to 30 min VAMP4-dependent manner. This link neurotransmission might serve substrate synaptic plasticity coupling distinct forms <b>SIGNIFICANCE STATEMENT</b> occurs (APs) shows significant intracellular levels. study, identify molecule (VAMP4) key component machinery maintains Ca²⁺-sensitive fraction events. Following brief intense activity, supports pool fuse spontaneously long term. We propose pathway acts shape associated based on previous activity history synapses.