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The Journal of Neuroscience, July 9, 2003, 23(14):6074-6085
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Maturation of EPSCs and Intrinsic Membrane Properties Enhances Precision at a Cerebellar Synapse
Laurence Cathala, Stephen Brickley, Stuart Cull-Candy, andMark Farrant Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
The timing of action potentials is an important determinant of information coding in the brain. The shape of the EPSP has a key influence on the temporal precision of spike generation. Here we use dynamic clamp recording and passive neuronal models to study how developmental changes in synaptic conductance waveform and intrinsic membrane properties combine to affect the EPSP and action potential generation in cerebellar granule cells. We recorded EPSCs at newly formed and mature mossy fiber–granule cell synapses. Both quantal and evoked currents showed a marked speeding of the AMPA receptor-mediated component. We also found evidence for age- and activity-dependent changes in the involvement of NMDA receptors. Although AMPA and NMDA receptors contributed to quantal EPSCs at immature synapses, multiquantal release was required to activate NMDA receptors at mature synapses, suggesting a developmental redistribution of NMDA receptors. These changes in the synaptic conductance waveform result in a faster rising EPSP and reduced spike latency in mature granule cells. Mature granule cells also have a significantly decreased input resistance, contributing to a faster decaying EPSP and a reduced spike jitter. We suggest that these concurrent developmental changes, which increase the temporal precision of EPSP-spike coupling, will increase the fidelity with which sensory information is processed within the input layer of the cerebellar cortex.
Key words: cerebellum; granule cell; EPSC; AMPA receptor; NMDA receptor; postnatal development; intrinsic membrane properties; EPSP
Received Mar. 20, 2003; revised Apr. 30, 2003; accepted May. 5, 2003.
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