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Desensitization properties of AMPA receptors at the cerebellar mossy fiber-granule cell synapse

DiGregorio, DA; Rothman, JS; Nielsen, TA; Silver, RA; (2007) Desensitization properties of AMPA receptors at the cerebellar mossy fiber-granule cell synapse. J NEUROSCI , 27 (31) 8344 - 8357. 10.1523/JNEUROSCI.2399-07.2007.

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Abstract

Native AMPA receptors (AMPARs) exhibit rapid and profound desensitization in the sustained presence of glutamate. Desensitization therefore contributes to short-term depression at synapses in which glutamate accumulates. At synapses that do not exhibit desensitization-dependent depression, AMPARs are thought to be protected against prolonged or repetitive exposure to synaptically released glutamate. At the cerebellar mossy fiber to granule cell (GC) synapse, in which high release probability and glutamate spillover produce a substantial buildup of glutamate concentration in the cleft ([Glut] cleft) during high-frequency transmission, only moderate desensitization of the phasic AMPAR EPSC occurs. To investigate how such currents are produced, we examined the kinetic properties of synaptic AMPARs in GCs using glutamate uncaging. Photolysis of 4-methoxy-7-nitroindolinyl-caged L-glutamate with large illumination spots produced step-like increases in [Glut] cleft that could be used to systematically probe AMPAR kinetics. At low levels of activation, synaptic AMPARs exhibited little desensitization. With larger activations, the desensitization time course became faster, but the level of desensitization was only weakly dependent on receptor occupancy. Indeed, a substantial desensitization-resistant current component remained (17%) in saturating glutamate. Photolysis with small illumination spots produced brief [Glut] cleft waveforms and transient AMPAR activations, similar to the EPSC current components. Paired-pulse uncaging with such spots revealed little desensitization after spillover-like activations and modest depression after activations that mimicked quantal and spillover components together. Our results show that GC AMPARs exhibit a resistance to desensitization at low occupancies and that this property is crucial for sustaining high-frequency transmission at a synapse in which glutamate accumulates.

Type: Article
Title: Desensitization properties of AMPA receptors at the cerebellar mossy fiber-granule cell synapse
DOI: 10.1523/JNEUROSCI.2399-07.2007
Keywords: synapse, spillover, AMPA receptor, cerebellum, desensitization, glutamate receptor, CA1 PYRAMIDAL NEURONS, MULTIPLE RELEASE SITES, SHORT-TERM DEPRESSION, GLUTAMATE RECEPTORS, COCHLEAR NUCLEUS, CLIMBING FIBER, TIME-COURSE, KINETIC-PROPERTIES, KAINATE RECEPTORS, DENDRITIC SPINES
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/177522
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