Takahashi, Michiko; (1996) Factors shaping excitatory synaptic currents in cerebellar Purkinje cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Glutamate is a major excitatory neurotransmitter in the central nervous system. Purkinje cells in the cerebellum receive two excitatory synaptic inputs, from climbing fibres and parallel fibres, at which excitatory postsynaptic currents (EPSCs) are mediated by amino-3-hydroxy-5-methyl-4-isoxazolepropinic acid (AMPA) receptors. The determinants of the EPSC magnitude and duration at the parallel fibre and climbing fibre to Purkinje cell synapses were studied. Adenosine and γ-aminobutyric acid (GABA) act on presynaptic receptors to inhibit neurotransmitter release from presynaptic terminals. They were found to decrease the EPSC amplitude more at the parallel than at the climbing fibre synapses. Adenosine and GABA also speeded the decay of the EPSCs. Applying an extracellular blocker of glutamate uptake prolonged the parallel and climbing fibre EPSCs. Blocking AMPA receptor desensitization also prolonged the decay time course of the EPSCs at both synapses. Purkinje cells, although postsynaptic neurons, are thought to express EAAC1 glutamate uptake carriers. The pharmacology, voltage-dependence and ion-dependence of a current attributable to this carrier was examined electrophysiologically. Altering the internal solution to block uptake specifically in Purkinje cells produced a prolongation of the climbing fibre EPSC. These data show that the AMPA-mediated postsynaptic current is shaped by presynaptic factors (the amount of glutamate released), by postsynaptic factors (receptor properties), and by the rate of glutamate removal from the synaptic cleft by uptake. When less glutamate is released into the cleft, it may be cleared from the cleft more quickly.

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