Glutamate receptors wander (top, yellow lines) in and around synapses (arrows). At synapses, naive receptors (bottom, green) replace desensitized ones (black).

CHOQUET/AAAS

Local diffusion of neurotransmitter receptors keep a neuron working fast, say Martin Heine, Daniel Choquet (CNRS, Bordeaux, France), and colleagues.

Synapses can become desensitized to quickly repeated stimulations. The receptors that receive signals such as glutamate become structurally altered by their ligands. So if a second stimulus comes too soon, the synapse is unable to react. Recovery from this desensitization—by reversing the structural changes—takes ∼100 ms. Yet somehow synapses can decipher two glutamate signals that arrive within just 10 ms of each other.

The findings from Heine et al. suggest that this quick response occurs because nearby receptors that have not yet met glutamate diffuse laterally within the membrane, replacing the desensitized receptors. When the authors limited receptor diffusion via receptor cross-linking or aggregation, the synapses lost their ability to respond to rapid repeated stimulation. Receptor mobility and recovery from desensitization was also blocked by increases in intracellular calcium.

Calcium influx is a normal response to the high-frequency stimulation that creates learning-associated long-term potentiation (LTP). The calcium activates kinases that might phosphorylate scaffolding proteins, perhaps thereby improving their ability to trap local receptors. As a result, synapses that have already achieved LTP mainly respond only to the slower stimulations that accompany typical information processing.

Choquet said his group didn't expect that receptor mobility would curtail desensitization, since diffusion is thought to be too slow. But he explains that it's possible because “smaller areas lead to a faster exchange. The neurotransmitter region is only a few hundred nanometers, so it can create an impact on a short time scale.”

Heine, M., et al.
2008
.
Science.
320
:
201
–205.