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Neurotransmitter secretion along growing nerve processes: comparison with synaptic vesicle exocytosis.

Zakharenko S, Chang S, O'Donoghue M, Popov SV - J. Cell Biol. (1999)

Bottom Line: We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar.These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion.Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics M/C 901, University of Illinois, Chicago, Illinois 60612, USA.

ABSTRACT
In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell.

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Paired pulse ratio  at the preformed synapse  (circles) and the middle axon  (squares). The ratio of the  ESC amplitude induced by  the second stimulus to that of  the first stimulus is plotted  for different interpulse intervals (ranging from 10 to 200  ms). For each neuron the ratio was determined as an average of at least five pairs of  ESCs. Data from eight (preformed synapse) and nine (middle axon) experiments were averaged and presented as mean ± SEM. No statistically significant  difference between the PPF was observed between the two series  of experiments (ANOVA).
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Figure 12: Paired pulse ratio at the preformed synapse (circles) and the middle axon (squares). The ratio of the ESC amplitude induced by the second stimulus to that of the first stimulus is plotted for different interpulse intervals (ranging from 10 to 200 ms). For each neuron the ratio was determined as an average of at least five pairs of ESCs. Data from eight (preformed synapse) and nine (middle axon) experiments were averaged and presented as mean ± SEM. No statistically significant difference between the PPF was observed between the two series of experiments (ANOVA).

Mentions: To compare the properties of synaptic vesicle recycling along the axon and at the nerve terminal, we used two assays for short-term synaptic plasticity of transmitter release. First, we measured the depression of evoked responses following repetitive high-frequency stimulation of the presynaptic cell. This depression is a characteristic of many synapses and reflects depletion of fusion-competent synaptic vesicles (Zucker, 1996). We compared the rate of depression during tetanic stimulation at the preformed synapses to that at the middle axonal segment (Fig. 11). Suprathreshold stimulation applied to the cell body at 5 Hz for 30 s led to an average of 22 ± 5% (n = 10) and 71 ± 18% (n = 12) reduction of the ESC amplitude in the preformed synapse and the middle axon, respectively. Thus, the rate of depression was significantly higher at the middle axon in comparison with the nerve terminal. In the second assay we measured paired pulse facilitation (PPF), the change in the amplitude of ESC when the presynaptic neuron is activated by two successive action potentials. This form of facilitation reflects the enhanced transmitter secretion resulting from the action of residual Ca2+ in the presynaptic neuron (Stoop and Poo, 1995; Zucker, 1996). Both at the presynaptic nerve terminal and at the middle axon, a PPF could be observed when the second pulse was applied <100 ms after the first one. The degree of PPF in recordings from the nerve terminal and the middle axon was similar for all interpulse intervals tested (Fig. 12).


Neurotransmitter secretion along growing nerve processes: comparison with synaptic vesicle exocytosis.

Zakharenko S, Chang S, O'Donoghue M, Popov SV - J. Cell Biol. (1999)

Paired pulse ratio  at the preformed synapse  (circles) and the middle axon  (squares). The ratio of the  ESC amplitude induced by  the second stimulus to that of  the first stimulus is plotted  for different interpulse intervals (ranging from 10 to 200  ms). For each neuron the ratio was determined as an average of at least five pairs of  ESCs. Data from eight (preformed synapse) and nine (middle axon) experiments were averaged and presented as mean ± SEM. No statistically significant  difference between the PPF was observed between the two series  of experiments (ANOVA).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2132923&req=5

Figure 12: Paired pulse ratio at the preformed synapse (circles) and the middle axon (squares). The ratio of the ESC amplitude induced by the second stimulus to that of the first stimulus is plotted for different interpulse intervals (ranging from 10 to 200 ms). For each neuron the ratio was determined as an average of at least five pairs of ESCs. Data from eight (preformed synapse) and nine (middle axon) experiments were averaged and presented as mean ± SEM. No statistically significant difference between the PPF was observed between the two series of experiments (ANOVA).
Mentions: To compare the properties of synaptic vesicle recycling along the axon and at the nerve terminal, we used two assays for short-term synaptic plasticity of transmitter release. First, we measured the depression of evoked responses following repetitive high-frequency stimulation of the presynaptic cell. This depression is a characteristic of many synapses and reflects depletion of fusion-competent synaptic vesicles (Zucker, 1996). We compared the rate of depression during tetanic stimulation at the preformed synapses to that at the middle axonal segment (Fig. 11). Suprathreshold stimulation applied to the cell body at 5 Hz for 30 s led to an average of 22 ± 5% (n = 10) and 71 ± 18% (n = 12) reduction of the ESC amplitude in the preformed synapse and the middle axon, respectively. Thus, the rate of depression was significantly higher at the middle axon in comparison with the nerve terminal. In the second assay we measured paired pulse facilitation (PPF), the change in the amplitude of ESC when the presynaptic neuron is activated by two successive action potentials. This form of facilitation reflects the enhanced transmitter secretion resulting from the action of residual Ca2+ in the presynaptic neuron (Stoop and Poo, 1995; Zucker, 1996). Both at the presynaptic nerve terminal and at the middle axon, a PPF could be observed when the second pulse was applied <100 ms after the first one. The degree of PPF in recordings from the nerve terminal and the middle axon was similar for all interpulse intervals tested (Fig. 12).

Bottom Line: We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar.These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion.Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics M/C 901, University of Illinois, Chicago, Illinois 60612, USA.

ABSTRACT
In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell.

Show MeSH
Related in: MedlinePlus