Target cell-specific involvement of presynaptic mitochondria in post-tetanic potentiation at hippocampal mossy fiber synapses.
Previous studies indicate that boutons from the same axon exhibit distinct Ca2+ dynamics depending on the postsynaptic targets. Mossy fibers of hippocampal granule cells innervate synaptic targets via morphologically distinct boutons. We investigated mitochondrial involvement in the generation of post-tetanic residual Ca2+ (Ca(res)) at large and small en passant mossy fiber boutons (MFBs). Mitochondria limited the [Ca2+]i build-up during high-frequency stimulation (HFS) at large MFBs, but not at small MFBs. The amount of Ca(res), quantified as a time integral of residual [Ca2+]i, was significantly larger at large MFBs than at small MFBs, and that at large MFBs was substantially attenuated by inhibitors of mitochondrial Ca2+ uniporter and mitochondrial Na+/Ca2+ exchanger (mitoNCX). In contrast, blockers of mitoNCX had no effect on the Ca(res) at small MFBs. Post-tetanic Ca(res) has been proposed as a mechanism for post-tetanic potentiation (PTP). We examined mitochondrial involvement in PTP at mossy fiber synapses on hilar mossy cells (MF-->MC synapse) and on hilar interneurons (MF-->HI synapse), which are presumably innervated via large and small MFBs, respectively. Consistent with the differential contribution of mitochondria to Ca(res) at large and small MFBs, mitoNCX blockers significantly reduced the PTP at the MF-->MC synapse, but not at the MF-->HI synapse. In contrast, protein kinase C (PKC) inhibitors significantly reduced the PTP at MF-->HI synapse, but not at the MF-->MC synapse. These results indicate that mitochondria- and PKC-dependent PTP are expressed at distinct hilar mossy fiber synapses depending on postsynaptic targets.
Lee
Doyun
D
National Research Laboratory for Cell Physiology, Department of Physiology, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul 110-799, Korea.
Lee
Kyu-Hee
KH
Ho
Won-Kyung
WK
Lee
Suk-Ho
SH
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology*; D014475:Uncoupling Agents / Q000494:pharmacology
D007476:Ionophores; D014475:Uncoupling Agents