The role of neuronal activity and transmitter release on synapse formation.
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.
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: email@example.com.Show MeSH
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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  and indeed NMDA-dependent dendritic filopodial growth . 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.
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: firstname.lastname@example.org.