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The role of neuronal activity and transmitter release on synapse formation.

Andreae LC, Burrone J - Curr. Opin. Neurobiol. (2014)

Bottom Line: Perhaps predictably, this turns out not to be a uniform process.It seems that different circuits, indeed specific synaptic connections, are differentially sensitive to the effects of activity.We examine possible ways in which neurotransmitter may drive synapse formation, and speculate on how the environment of the developing brain may allow a different spatiotemporal range for neuronal activity to operate in the generation of connectivity.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, New Hunt's House, 4th Floor, Guy's Hospital Campus, London SE1 1UL, UK. Electronic address: laura.andreae@kcl.ac.uk.

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The role of the neurotransmitter glutamate in synapse formation. (a) Glutamate can induce the formation of functional postsynaptic spines. The diagram shows a developing neuron in the cortex with a cell body (green) and apical dendrites (gray). The inset shows a zoomed in section of the dendrite (red box), which contains an existing spine (top drawing). Glutamate is uncaged locally with a laser (blue circle), resulting in the emergence of a new postsynaptic spine. Adapted from [53]. (b) Long range communication between neurons in developing circuits. Growing axons release neurotransmitter before they form any synaptic connections (indicated by graded blue signal from axons). Filopodia from neighbouring neurons may be able to sense this neurotransmitter at a distance (indicated by the graded green response in filopodia). Inset: the release of neurotransmitter, such as glutamate, from presynaptic vesicles (blue) clustered along a growing axon could activate distant dendritic receptors (green), such as NMDA receptors, resulting in possible calcium influx and plasticity (top drawing). Such a form of long-range communication, distinct from local synaptic transmission in mature synapses (bottom drawing) could provide information for circuit assembly and synapse formation. The spatial extent of this form of communication (d) may well be larger than the few nanometers of mature synapses and may help instruct postsynaptic filopodia and dendrites during the process of synaptogenesis.
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fig0010: The role of the neurotransmitter glutamate in synapse formation. (a) Glutamate can induce the formation of functional postsynaptic spines. The diagram shows a developing neuron in the cortex with a cell body (green) and apical dendrites (gray). The inset shows a zoomed in section of the dendrite (red box), which contains an existing spine (top drawing). Glutamate is uncaged locally with a laser (blue circle), resulting in the emergence of a new postsynaptic spine. Adapted from [53]. (b) Long range communication between neurons in developing circuits. Growing axons release neurotransmitter before they form any synaptic connections (indicated by graded blue signal from axons). Filopodia from neighbouring neurons may be able to sense this neurotransmitter at a distance (indicated by the graded green response in filopodia). Inset: the release of neurotransmitter, such as glutamate, from presynaptic vesicles (blue) clustered along a growing axon could activate distant dendritic receptors (green), such as NMDA receptors, resulting in possible calcium influx and plasticity (top drawing). Such a form of long-range communication, distinct from local synaptic transmission in mature synapses (bottom drawing) could provide information for circuit assembly and synapse formation. The spatial extent of this form of communication (d) may well be larger than the few nanometers of mature synapses and may help instruct postsynaptic filopodia and dendrites during the process of synaptogenesis.

Mentions: Studies from the field of synaptic plasticity have revealed that high levels of activity (able to induce long-term potentiation of synaptic strength) can induce new spine formation [49] and indeed NMDA-dependent dendritic filopodial growth [50]. It seems intuitive that Hebbian-like plasticity mechanisms could play a role during earlier synapse development [51,52]. A more recent study has now shown that neurotransmitter can directly induce the de novo formation of mature spines during development in cortical neurons (Figure 2a) [53••]. Either focal uncaging of caged glutamate close to a stretch of dendrite (less than 1 μm away) or high frequency stimulation resulted in the local growth of spines very rapidly (within 6 s of the uncaging protocol). This effect was dependent on NMDA receptor activation. Surprisingly, the new spines did not emerge as filopodia, but as mature spines, both structurally and functionally, expressing receptors and channels that allows their rapid integration into the circuit. How these experiments compare to the earlier stages of synapse formation where immature axons have not yet established any synaptic contact, is not yet clear. Also, whether neurotransmitter release could act at a distance, and how far a release site needs to be to activate postsynaptic receptors, remains unknown. Future studies are likely to illuminate further possible mechanisms for activity-driven synaptogenesis.


The role of neuronal activity and transmitter release on synapse formation.

Andreae LC, Burrone J - Curr. Opin. Neurobiol. (2014)

The role of the neurotransmitter glutamate in synapse formation. (a) Glutamate can induce the formation of functional postsynaptic spines. The diagram shows a developing neuron in the cortex with a cell body (green) and apical dendrites (gray). The inset shows a zoomed in section of the dendrite (red box), which contains an existing spine (top drawing). Glutamate is uncaged locally with a laser (blue circle), resulting in the emergence of a new postsynaptic spine. Adapted from [53]. (b) Long range communication between neurons in developing circuits. Growing axons release neurotransmitter before they form any synaptic connections (indicated by graded blue signal from axons). Filopodia from neighbouring neurons may be able to sense this neurotransmitter at a distance (indicated by the graded green response in filopodia). Inset: the release of neurotransmitter, such as glutamate, from presynaptic vesicles (blue) clustered along a growing axon could activate distant dendritic receptors (green), such as NMDA receptors, resulting in possible calcium influx and plasticity (top drawing). Such a form of long-range communication, distinct from local synaptic transmission in mature synapses (bottom drawing) could provide information for circuit assembly and synapse formation. The spatial extent of this form of communication (d) may well be larger than the few nanometers of mature synapses and may help instruct postsynaptic filopodia and dendrites during the process of synaptogenesis.
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4127784&req=5

fig0010: The role of the neurotransmitter glutamate in synapse formation. (a) Glutamate can induce the formation of functional postsynaptic spines. The diagram shows a developing neuron in the cortex with a cell body (green) and apical dendrites (gray). The inset shows a zoomed in section of the dendrite (red box), which contains an existing spine (top drawing). Glutamate is uncaged locally with a laser (blue circle), resulting in the emergence of a new postsynaptic spine. Adapted from [53]. (b) Long range communication between neurons in developing circuits. Growing axons release neurotransmitter before they form any synaptic connections (indicated by graded blue signal from axons). Filopodia from neighbouring neurons may be able to sense this neurotransmitter at a distance (indicated by the graded green response in filopodia). Inset: the release of neurotransmitter, such as glutamate, from presynaptic vesicles (blue) clustered along a growing axon could activate distant dendritic receptors (green), such as NMDA receptors, resulting in possible calcium influx and plasticity (top drawing). Such a form of long-range communication, distinct from local synaptic transmission in mature synapses (bottom drawing) could provide information for circuit assembly and synapse formation. The spatial extent of this form of communication (d) may well be larger than the few nanometers of mature synapses and may help instruct postsynaptic filopodia and dendrites during the process of synaptogenesis.
Mentions: Studies from the field of synaptic plasticity have revealed that high levels of activity (able to induce long-term potentiation of synaptic strength) can induce new spine formation [49] and indeed NMDA-dependent dendritic filopodial growth [50]. It seems intuitive that Hebbian-like plasticity mechanisms could play a role during earlier synapse development [51,52]. A more recent study has now shown that neurotransmitter can directly induce the de novo formation of mature spines during development in cortical neurons (Figure 2a) [53••]. Either focal uncaging of caged glutamate close to a stretch of dendrite (less than 1 μm away) or high frequency stimulation resulted in the local growth of spines very rapidly (within 6 s of the uncaging protocol). This effect was dependent on NMDA receptor activation. Surprisingly, the new spines did not emerge as filopodia, but as mature spines, both structurally and functionally, expressing receptors and channels that allows their rapid integration into the circuit. How these experiments compare to the earlier stages of synapse formation where immature axons have not yet established any synaptic contact, is not yet clear. Also, whether neurotransmitter release could act at a distance, and how far a release site needs to be to activate postsynaptic receptors, remains unknown. Future studies are likely to illuminate further possible mechanisms for activity-driven synaptogenesis.

Bottom Line: Perhaps predictably, this turns out not to be a uniform process.It seems that different circuits, indeed specific synaptic connections, are differentially sensitive to the effects of activity.We examine possible ways in which neurotransmitter may drive synapse formation, and speculate on how the environment of the developing brain may allow a different spatiotemporal range for neuronal activity to operate in the generation of connectivity.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, New Hunt's House, 4th Floor, Guy's Hospital Campus, London SE1 1UL, UK. Electronic address: laura.andreae@kcl.ac.uk.

Show MeSH
Related in: MedlinePlus