The ubiquitous nature of multivesicular release

Rudolph, Stephanie; Tsai, Ming-Chi; Gersdorff, Henrique von; Wadiche, Jacques I.

doi:10.1016/j.tins.2015.05.008

Cited by 94 publications

(141 citation statements)

References 164 publications

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“…In contrast, the same type of axon terminals in human contain on average 6 functional release sites, demonstrating that here multivesicular release (MVR; (Rudolph et al, 2015) is the main mode of operation. However, it is important to note that our data clearly demonstrate large variability in the AZ area in both species and that the number of docked vesicles and docking sites correlates with the AZ area.…”

Section: Discussionmentioning

confidence: 99%

Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles

Molnár

Rózsa

Baka

et al. 2016

eLife

108

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Classic theories link cognitive abilities to synaptic properties and human-specific biophysical features of synapses might contribute to the unparalleled performance of the human cerebral cortex. Paired recordings and multiple probability fluctuation analysis revealed similar quantal sizes, but 4-times more functional release sites in human pyramidal cell to fast-spiking interneuron connections compared to rats. These connections were mediated on average by three synaptic contacts in both species. Each presynaptic active zone (AZ) contains 6.2 release sites in human, but only 1.6 in rats. Electron microscopy (EM) and EM tomography showed that an AZ harbors 4 docked vesicles in human, but only a single one in rats. Consequently, a Katz’s functional release site occupies ~0.012 μm2 in the human presynaptic AZ and ~0.025 μm2 in the rat. Our results reveal a robust difference in the biophysical properties of a well-defined synaptic connection of the cortical microcircuit of human and rodents.DOI: http://dx.doi.org/10.7554/eLife.18167.001

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Section: Discussionmentioning

confidence: 99%

Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles

Molnár

Rózsa

Baka

et al. 2016

eLife

108

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“…At some central excitatory and inhibitory synapses, multivesicular release occurs when more than one synaptic vesicle is released from a terminal in response to an action potential (Rudolph et al . ). In addition, presynaptic metabotropic receptor activation modulates multivesicular release within a number of brain regions (Takahashi et al .…”

Section: Introductionmentioning

confidence: 97%

Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses

Aubrey

Drew

Jeong

et al. 2016

The Journal of Physiology

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Key pointsr The midbrain periaqueductal grey (PAG) forms part of an endogenous analgesic system which is tightly regulated by the neurotransmitter GABA.r The role of endocannabinoids in regulating GABAergic control of this system was examined in rat PAG slices.r Under basal conditions GABAergic neurotransmission onto PAG output neurons was multivesicular.r Activation of the endocannabinoid system reduced GABAergic inhibition by reducing the probability of release and by shifting release to a univesicular mode.r Blockade of endocannabinoid system unmasked a tonic control over the probability and mode of GABA release.r These findings provides a mechanistic foundation for the control of the PAG analgesic system by disinhibition. AbstractThe midbrain periaqueductal grey (PAG) has a crucial role in coordinating endogenous analgesic responses to physiological and psychological stressors. Endocannabinoids are thought to mediate a form of stress-induced analgesia within the PAG by relieving GABAergic inhibition of output neurons, a process known as disinhibition. This disinhibition is thought to be achieved by a presynaptic reduction in GABA release probability. We examined whether other mechanisms have a role in endocannabinoid modulation of GABAergic synaptic transmission within the rat PAG. The group I mGluR agonist DHPG ((R,S)-3,5-dihydroxyphenylglycine) inhibited evoked IPSCs and increased their paired pulse ratio in normal external Ca 2+ , and when release probability was reduced by lowering Ca 2+ . However, the effect of DHPG on the coefficient of variation and kinetics of evoked IPSCs differed between normal and low Ca 2+ . Lowering external Ca 2+ had a similar effect on evoked IPSCs to that observed for DHPG in normal external Ca 2+ . The low affinity GABA A receptor antagonist TPMPA ((1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid) inhibited evoked IPSCs to a greater extent in low than in normal Ca 2+ . Together these findings indicate that the normal mode of GABA release is multivesicular within the PAG, and that DHPG and lowering external Ca 2+ switch this to a univesicular mode. The effects of DHPG were mediated by mGlu5 receptor engagement of the retrograde endocannabinoid system. Blockade of endocannabinoid breakdown produced a similar shift in the mode of release. We conclude that endocannabinoids control both the mode and the probability of GABA release within the PAG. * K.R.A. and G.M.D. contributed equally to this work.

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“…Ezzel szemben az emberi agykérgi méréseinkből származó adatok szerint ezekre a szinapszisokra multivezikuláris neurotranszmitter felszabadulás jellemző (Rudolph et al, 2015). Fontos megemlítenünk, hogy eredményeink mindkét faj esetében nagy szórást mutatnak, és az aktív zónák területe pozitívan korrelál a rajtuk található dokkolt vezikulák számával.…”

Section: A Humán Kosársejtekre éRkező Helyi Serkentő Szinaptikus Bemeunclassified

“…Fontos megemlítenünk, hogy eredményeink mindkét faj esetében nagy szórást mutatnak, és az aktív zónák területe pozitívan korrelál a rajtuk található dokkolt vezikulák számával. Így a multivezikuláris neurotranszmitter felszabadítás az agykéregben nem humán specifikus, hanem előfordul a rágcsálók nagyobb területű aktív zónáiban is (Rudolph et al, 2015).…”

Section: A Humán Kosársejtekre éRkező Helyi Serkentő Szinaptikus Bemeunclassified

Agykérgi szinapszisok összehasonlító vizsgálata és a szinapszisszám változása posztpartum depresszióban

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The ubiquitous nature of multivesicular release

Cited by 94 publications

References 164 publications

Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles

Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles

Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses

Agykérgi szinapszisok összehasonlító vizsgálata és a szinapszisszám változása posztpartum depresszióban

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