Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission

• Published in: Nature neuroscience Vol. 18; no. 2; pp. 219 - 226
• Main Authors: Murphy-Royal, Ciaran, Dupuis, Julien P, Varela, Juan A, Panatier, Aude, Pinson, Benoît, Baufreton, Jérôme, Groc, Laurent, Oliet, Stéphane H R
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2015; Nature Publishing Group
• Subjects: 14; 14/63; 631/378/2587; 631/378/2596/1308; 631/378/548; Animal Genetics and Genomics; Animals; Astrocytes - metabolism; Behavioral Sciences; Biological Techniques; Biomedicine; Carrier proteins; Diffusion; Excitatory Amino Acid Transporter 2 - metabolism; Female; Genetic aspects; Glutamate; Glutamic Acid - metabolism; Hippocampus - metabolism; Life Sciences; Male; Neural transmission; Neurobiology; Neurons and Cognition; Neurosciences; Physiological aspects; Rats; Rats, Sprague-Dawley; Synaptic Transmission - physiology; France
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.3901

The authors find that glutamate release increases the diffusion of the astrocytic glutamate transporter GLT-1 in the plasma membrane. This activity-dependent increase in mobility facilitates glutamate clearance from the synaptic cleft, which influences the kinetics of excitatory post-synaptic events in rat hippocampal neurons. Control of the glutamate time course in the synapse is crucial for excitatory transmission. This process is mainly ensured by astrocytic transporters, high expression of which is essential to compensate for their slow transport cycle. Although molecular mechanisms regulating transporter intracellular trafficking have been identified, the relationship between surface transporter dynamics and synaptic function remains unexplored. We found that GLT-1 transporters were highly mobile on rat astrocytes. Surface diffusion of GLT-1 was sensitive to neuronal and glial activities and was strongly reduced in the vicinity of glutamatergic synapses, favoring transporter retention. Notably, glutamate uncaging at synaptic sites increased GLT-1 diffusion, displacing transporters away from this compartment. Functionally, impairing GLT-1 membrane diffusion through cross-linking in vitro and in vivo slowed the kinetics of excitatory postsynaptic currents, indicative of a prolonged time course of synaptic glutamate. These data provide, to the best of our knowledge, the first evidence for a physiological role of GLT-1 surface diffusion in shaping synaptic transmission.