Journal
JOURNAL OF NEUROSCIENCE
Volume 32, Issue 41, Pages 14294-14304Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.6104-11.2012
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Funding
- Deutsche Forschungsgemeinschaft [TR 3/B10]
- European Union (European Research Council Advanced Grant)
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The coupling between presynaptic Ca2+ channels and Ca2+ sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca2+ channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic opening of presynaptic Ca2+ channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca2+ concentration and the unselective Ca2+ channel blocker Cd2+ reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by similar to 50%, suggesting that the opening of presynaptic Ca2+ channels contributes to spontaneous release. Application of the selective P/Q-type Ca2+ channel blocker omega-agatoxin IVa had no detectable effects, whereas both the N-type blocker omega-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca2+ chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca2+-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB1 receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of omega-conotoxin GVIa, suggesting that a major fraction of Ca2+-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca2+ channels may be important for hippocampal information processing.
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