Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling Journal Article

Author(s): Goswami, Sarit P; Bucurenciu, Iancu; Jonas, Peter
Article Title: Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling
Affiliation IST Austria
Abstract: The coupling between presynaptic Ca^(2+) channels and Ca^(2+) 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 Ca^(2+) 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 Ca^(2+) 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 Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency, suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing.
Journal Title: Journal of Neuroscience
Volume: 32
Issue 41
ISSN: 1529-2401
Publisher: Society for Neuroscience  
Date Published: 2012-10-10
Start Page: 14294
End Page: 14304
Sponsor: This work was supported by grants from the Deutsche Forschungsgemeinschaft (TR 3/B10, Leibniz program, GSC-4 Spemann Graduate School) and the European Union (European Research Council Advanced Grant).
DOI: 10.1523/JNEUROSCI.6104-11.2012
Open access: yes (repository)