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Presynaptic nanodomains: a tale of two synapses.

Wang LY, Augustine GJ - Front Cell Neurosci (2015)

Bottom Line: At the squid synapse, there are three main lines of experimental evidence for nanodomain signaling.Second, low-affinity calcium indicators, calcium chelators, and uncaging of calcium all suggest that presynaptic calcium concentrations are as high as hundreds of micromolar, which is more compatible with a nanodomain type of calcium signal.Taken together, data from these provide a compelling argument that nanodomain calcium signaling gates very rapid transmitter release.

View Article: PubMed Central - PubMed

Affiliation: Program in Neurosciences and Mental Health, SickKids Research Institute Toronto, Canada ; Department of Physiology, University of Toronto Toronto, Canada.

ABSTRACT
Here we summarize the evidence from two "giant" presynaptic terminals-the squid giant synapse and the mammalian calyx of Held-supporting the involvement of nanodomain calcium signals in triggering of neurotransmitter release. At the squid synapse, there are three main lines of experimental evidence for nanodomain signaling. First, changing the size of the unitary calcium channel current by altering external calcium concentration causes a non-linear change in transmitter release, while changing the number of open channels by broadening the presynaptic action potential causes a linear change in release. Second, low-affinity calcium indicators, calcium chelators, and uncaging of calcium all suggest that presynaptic calcium concentrations are as high as hundreds of micromolar, which is more compatible with a nanodomain type of calcium signal. Finally, neurotransmitter release is much less affected by the slow calcium chelator, ethylene glycol tetraacetic acid (EGTA), in comparison to the rapid chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Similarly, as the calyx of Held synapse matures, EGTA becomes less effective in attenuating transmitter release while the number of calcium channels required to trigger a single fusion event declines. This suggests a developmental transformation of microdomain to nanodomain coupling between calcium channels and transmitter release. Calcium imaging and uncaging experiments, in combination with simulations of calcium diffusion, indicate the peak calcium concentration seen by presynaptic calcium sensors reaches at least tens of micromolar at the calyx of Held. Taken together, data from these provide a compelling argument that nanodomain calcium signaling gates very rapid transmitter release.

No MeSH data available.


Related in: MedlinePlus

Age-dependent morphological remodeling of the calyx of Held. Images of the 3-dimensional structure of P8 (A) and P17 (B) calyces filled with the fluorescent marker biotinylated dextran amine (courtesy of G. Grande). The diameter of each calyx sphere is approximately 15–20 micrometers.
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Figure 5: Age-dependent morphological remodeling of the calyx of Held. Images of the 3-dimensional structure of P8 (A) and P17 (B) calyces filled with the fluorescent marker biotinylated dextran amine (courtesy of G. Grande). The diameter of each calyx sphere is approximately 15–20 micrometers.

Mentions: The calyx of Held synapse undergoes tremendous morphological remodeling in the course of its development, with its presynaptic terminal transforming from a spoon- or club-like structure with thin filopodia before the onset of hearing (P11–12) to a highly digitated structure with stalks and swellings containing a total of 500–800 active zones at maturity (>P16; Figure 5). Such structural transformations are thought to be important for supporting release and replenishment of synaptic vesicles (SVs), as well as facilitating clearance of neurotransmitter to alleviate postsynaptic receptor desensitization during high-frequency transmission (Trussell, 1999; von Gersdorff and Borst, 2002). In practice, calyces become less visible in brainstem slices for patch-clamping as myelination progresses during maturation, meaning that most early studies on the calyx of Held synapse focused on immature synapses (e.g., P8–11).


Presynaptic nanodomains: a tale of two synapses.

Wang LY, Augustine GJ - Front Cell Neurosci (2015)

Age-dependent morphological remodeling of the calyx of Held. Images of the 3-dimensional structure of P8 (A) and P17 (B) calyces filled with the fluorescent marker biotinylated dextran amine (courtesy of G. Grande). The diameter of each calyx sphere is approximately 15–20 micrometers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306312&req=5

Figure 5: Age-dependent morphological remodeling of the calyx of Held. Images of the 3-dimensional structure of P8 (A) and P17 (B) calyces filled with the fluorescent marker biotinylated dextran amine (courtesy of G. Grande). The diameter of each calyx sphere is approximately 15–20 micrometers.
Mentions: The calyx of Held synapse undergoes tremendous morphological remodeling in the course of its development, with its presynaptic terminal transforming from a spoon- or club-like structure with thin filopodia before the onset of hearing (P11–12) to a highly digitated structure with stalks and swellings containing a total of 500–800 active zones at maturity (>P16; Figure 5). Such structural transformations are thought to be important for supporting release and replenishment of synaptic vesicles (SVs), as well as facilitating clearance of neurotransmitter to alleviate postsynaptic receptor desensitization during high-frequency transmission (Trussell, 1999; von Gersdorff and Borst, 2002). In practice, calyces become less visible in brainstem slices for patch-clamping as myelination progresses during maturation, meaning that most early studies on the calyx of Held synapse focused on immature synapses (e.g., P8–11).

Bottom Line: At the squid synapse, there are three main lines of experimental evidence for nanodomain signaling.Second, low-affinity calcium indicators, calcium chelators, and uncaging of calcium all suggest that presynaptic calcium concentrations are as high as hundreds of micromolar, which is more compatible with a nanodomain type of calcium signal.Taken together, data from these provide a compelling argument that nanodomain calcium signaling gates very rapid transmitter release.

View Article: PubMed Central - PubMed

Affiliation: Program in Neurosciences and Mental Health, SickKids Research Institute Toronto, Canada ; Department of Physiology, University of Toronto Toronto, Canada.

ABSTRACT
Here we summarize the evidence from two "giant" presynaptic terminals-the squid giant synapse and the mammalian calyx of Held-supporting the involvement of nanodomain calcium signals in triggering of neurotransmitter release. At the squid synapse, there are three main lines of experimental evidence for nanodomain signaling. First, changing the size of the unitary calcium channel current by altering external calcium concentration causes a non-linear change in transmitter release, while changing the number of open channels by broadening the presynaptic action potential causes a linear change in release. Second, low-affinity calcium indicators, calcium chelators, and uncaging of calcium all suggest that presynaptic calcium concentrations are as high as hundreds of micromolar, which is more compatible with a nanodomain type of calcium signal. Finally, neurotransmitter release is much less affected by the slow calcium chelator, ethylene glycol tetraacetic acid (EGTA), in comparison to the rapid chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Similarly, as the calyx of Held synapse matures, EGTA becomes less effective in attenuating transmitter release while the number of calcium channels required to trigger a single fusion event declines. This suggests a developmental transformation of microdomain to nanodomain coupling between calcium channels and transmitter release. Calcium imaging and uncaging experiments, in combination with simulations of calcium diffusion, indicate the peak calcium concentration seen by presynaptic calcium sensors reaches at least tens of micromolar at the calyx of Held. Taken together, data from these provide a compelling argument that nanodomain calcium signaling gates very rapid transmitter release.

No MeSH data available.


Related in: MedlinePlus