Synaptic transmission: Diffusion to speed up recovery
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Fast, repetitive synaptic stimulation wears a neuron out. The decrease in response to neurotransmitter that ensues, known as postsynaptic depression, is typically attributed to receptor desensitization. Heine and colleagues now show that the recovery of AMPARs (α-amino- 3-hydroxy-5-methyl-4-isoxazole propionic acid receptors) from post- synaptic depression does not depend solely on receptor kinetics and neurotransmitter-clearance mecha- nisms, but also on lateral membrane diffusion. By using fluorescence recovery after photobleaching (FRAP) and single quantum dots (fluorescent nanocrystals of semiconductor material) in cultured neurons and brain slices, the authors showed that AMPARs diffuse rapidly on the sur- face of neurons and are continuously exchanged between synaptic and extrasynaptic sites. Moreover, this mobility contributed to the recovery from postsynaptic depression: cross- linking AMPARs with antibodies reduced the amplitude of the second of two successive evoked excitatory postsynaptic currents (EPSCs), as well as the response to direct, local application of glutamate, compared with cells in which AMPARs were not immobilized. To determine the respective contributions of receptor mobility and resensitization to postsynaptic depression recovery, the authors examined clustered and diffuse GluR1-containing AMPARs. Synapses with clustered GluR1- containing AMPARs displayed much stronger depression than those with diffuse receptors, even in the pres- ence of cross-linking antibodies, suggesting that recovery is domi- nated by diffusion when mobility is high but that receptor kinetics are particularly influential when mobility is restricted. This finding highlights the impor- tance of endogenous mechanisms that regulate receptor mobility on recovery from postsynaptic depres- sion and, hence, synaptic transmis- sion. Indeed, the authors showed that increases in intracellular Ca 2+ , induced by activating NMDARs (N-methyl-d-aspartate receptors), reduced AMPAR mobility and slowed postsynaptic depression recovery. Although receptor diffusion is known to be implicated in receptor turnover and neurotransmission on the second-to-minute timescale, this study demonstrates its contribu- tion to the regulation of synaptic transmission in the millisecond time range. Based on the rates of mobility observed, 30% of the recep- tors at a synapse could be replaced within 10 ms — this exchange of desensitized receptors with ‘fresh’ ones from within the synapse or from extrasynaptic sites could be crucial to sustain fast excitatory synaptic transmission. Monica Hoyos Flight ORIGINAL RESEARCH PAPER Heine, M. et al. Surface mobility of postsynaptic AMPARs tunes synaptic transmission. Science 320, 201–205 (2008) SYNAPTIC TRANSMISSION Diffusion to speed up recovery RESEARCH HIGHLIGHTS NATURE REVIEWS | NEUROSCIENCE VOLUME 9 | JUNE 2008 © 2008 Nature Publishing Group
Transcript of Synaptic transmission: Diffusion to speed up recovery
Fast, repetitive synaptic stimulation wears a neuron out. The decrease in response to neurotransmitter that ensues, known as postsynaptic depression, is typically attributed to receptor desensitization. Heine and colleagues now show that the recovery of AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors) from post-synaptic depression does not depend solely on receptor kinetics and neurotransmitter-clearance mecha-nisms, but also on lateral membrane diffusion.
By using fluorescence recovery after photobleaching (FRAP) and single quantum dots (fluorescent nanocrystals of semiconductor material) in cultured neurons and brain slices, the authors showed that AMPARs diffuse rapidly on the sur-face of neurons and are continuously exchanged between synaptic and extrasynaptic sites. Moreover, this mobility contributed to the recovery from postsynaptic depression: cross-linking AMPARs with antibodies reduced the amplitude of the second of two successive evoked excitatory postsynaptic currents (EPSCs), as well as the response to direct, local application of glutamate, compared with cells in which AMPARs were not immobilized.
To determine the respective contributions of receptor mobility and resensitization to postsynaptic depression recovery, the authors examined clustered and diffuse GluR1-containing AMPARs. Synapses with clustered GluR1-containing AMPARs displayed much stronger depression than those with diffuse receptors, even in the pres-ence of cross-linking antibodies, suggesting that recovery is domi-nated by diffusion when mobility is high but that receptor kinetics are particularly influential when mobility is restricted.
This finding highlights the impor-tance of endogenous mechanisms that regulate receptor mobility on recovery from postsynaptic depres-sion and, hence, synaptic transmis-sion. Indeed, the authors showed that increases in intracellular Ca2+, induced by activating NMDARs (N-methyl-d-aspartate receptors), reduced AMPAR mobility and slowed postsynaptic depression recovery.
Although receptor diffusion is known to be implicated in receptor turnover and neurotransmission on the second-to-minute timescale, this study demonstrates its contribu-tion to the regulation of synaptic transmission in the millisecond time range. Based on the rates of
mobility observed, 30% of the recep-tors at a synapse could be replaced within 10 ms — this exchange of desensitized receptors with ‘fresh’ ones from within the synapse or from extrasynaptic sites could be crucial to sustain fast excitatory synaptic transmission.
Monica Hoyos Flight
ORIGINAL RESEARCH PAPER Heine, M. et al. Surface mobility of postsynaptic AMPARs tunes synaptic transmission. Science 320, 201–205 (2008)
S Y N A P T I C T R A N S m I S S I O N
Diffusion to speed up recovery
R e s e a R c h h i g h l i g h t s
NATuRE REvIEwS | neuroscience voluME 9 | juNE 2008
© 2008 Nature Publishing Group
