Differential modulation of short-term plasticity at hippocampal mossy fiber and Schaffer collateral synapses by mitochondrial Ca2
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Differential modulation of short-term plasticity at hippocampal mossy fiber and Schaffer collateral synapses by mitochondrial Ca2. / Lee, Sang Hun; Lutz, David; Drexler, Dagmar; Frotscher, Michael; Shen, Jie.
in: PLOS ONE, Jahrgang 15, Nr. 10, e0240610, 13.10.2020.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Differential modulation of short-term plasticity at hippocampal mossy fiber and Schaffer collateral synapses by mitochondrial Ca2
AU - Lee, Sang Hun
AU - Lutz, David
AU - Drexler, Dagmar
AU - Frotscher, Michael
AU - Shen, Jie
PY - 2020/10/13
Y1 - 2020/10/13
N2 - Presynaptic mitochondrial Ca2+ plays a critical role in the regulation of synaptic transmission and plasticity. The presynaptic bouton of the hippocampal mossy fiber (MF) is much larger in size than that of the Schaffer collateral (SC) synapse. Here we compare the structural and physiological characteristics of MF and SC presynaptic boutons to reveal functional and mechanistic differences between these two synapses. Our quantitative ultrastructural analysis using electron microscopy show many more mitochondria in MF presynaptic bouton cross-section profiles compared to SC boutons. Consistent with these results, post-tetanic potentiation (PTP), a form of presynaptic short-term plasticity dependent on mitochondrial Ca2+, is reduced by inhibition of mitochondrial Ca2+ release at MF synapses but not at SC synapses. However, blockade of mitochondrial Ca2+ release results in reduction of PTP at SC synapses by disynaptic MF stimulation. Furthermore, inhibition of mitochondrial Ca2+ release selectively decreases frequency facilitation evoked by short trains of presynaptic stimulation at MF synapses, while having no effect at SC synapses. Moreover, depletion of ER Ca2+ stores leads to reduction of PTP at MF synapses, but PTP is unaffected by ER Ca2+ depletion at SC synapses. These findings show that MF and SC synapses differ in presynaptic mitochondrial content as well as mitochondrial Ca2+ dependent synaptic plasticity, highlighting differential regulatory mechanisms of presynaptic plasticity at MF and SC synapses.
AB - Presynaptic mitochondrial Ca2+ plays a critical role in the regulation of synaptic transmission and plasticity. The presynaptic bouton of the hippocampal mossy fiber (MF) is much larger in size than that of the Schaffer collateral (SC) synapse. Here we compare the structural and physiological characteristics of MF and SC presynaptic boutons to reveal functional and mechanistic differences between these two synapses. Our quantitative ultrastructural analysis using electron microscopy show many more mitochondria in MF presynaptic bouton cross-section profiles compared to SC boutons. Consistent with these results, post-tetanic potentiation (PTP), a form of presynaptic short-term plasticity dependent on mitochondrial Ca2+, is reduced by inhibition of mitochondrial Ca2+ release at MF synapses but not at SC synapses. However, blockade of mitochondrial Ca2+ release results in reduction of PTP at SC synapses by disynaptic MF stimulation. Furthermore, inhibition of mitochondrial Ca2+ release selectively decreases frequency facilitation evoked by short trains of presynaptic stimulation at MF synapses, while having no effect at SC synapses. Moreover, depletion of ER Ca2+ stores leads to reduction of PTP at MF synapses, but PTP is unaffected by ER Ca2+ depletion at SC synapses. These findings show that MF and SC synapses differ in presynaptic mitochondrial content as well as mitochondrial Ca2+ dependent synaptic plasticity, highlighting differential regulatory mechanisms of presynaptic plasticity at MF and SC synapses.
KW - Animals
KW - Calcium/metabolism
KW - Calcium Signaling/drug effects
KW - Excitatory Postsynaptic Potentials/drug effects
KW - Hippocampus/cytology
KW - Male
KW - Mice
KW - Microscopy, Electron
KW - Mitochondria/drug effects
KW - Mossy Fibers, Hippocampal/drug effects
KW - Neuronal Plasticity/drug effects
KW - Onium Compounds/pharmacology
KW - Organophosphorus Compounds/pharmacology
KW - Patch-Clamp Techniques
KW - Thiazepines/pharmacology
U2 - 10.1371/journal.pone.0240610
DO - 10.1371/journal.pone.0240610
M3 - SCORING: Journal article
C2 - 33049001
VL - 15
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 10
M1 - e0240610
ER -