Fast- and slow-rising AMPA receptor-mediated EPSCs occur at central synapses. Fast-rising EPSCs are thought to be mediated by rapid local release of glutamate. However, two controversial mechanisms have been proposed to underlie slow-rising EPSCs: prolonged local release of transmitter via a fusion pore, and spillover of transmitter released rapidly from distant sites. We have investigated the mechanism underlying slow-rising EPSCs and the diffusion coefficient of glutamate in the synaptic cleft (Dglut) at cerebellar mossy fiber-granule cell synapses using a combination of diffusion modeling and patch-clamp recording. Simulations show that modulating Dglut has different effects on the peak amplitudes and time courses of EPSCs mediated by these two mechanisms. Slowing diffusion with the macromolecule dextran slowed slow-rising EPSCs and had little effect on their amplitude, indicating that glutamate spillover underlies these currents. Our results also suggest that under control conditions Dglut is approximately 3-fold lower than in free solution.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neuron.2004.04.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Role of glutamate transporters in excitatory synapses in cerebellar Purkinje cells].
Brain Nerve
July 2007
Regent Office, Gunma University, 4-2 Aramaki, Maebashi, Gunma 371-8510, Japan.
Glutamate transporters play critical roles in the maintenance of low extracellular concentrations of glutamate, which protects neurons from excitotoxic injury. The activity of these transporters also restricts the amplitude and duration of excitatory postsynaptic currents (EPSCs) in glutamatergic synapses. In the CNS, five distinct glutamate transporters (GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4 and EAAT5) have been cloned.
View Article and Find Full Text PDFGlial glutamate transporters maintain one-to-one relationship at the climbing fiber-Purkinje cell synapse by preventing glutamate spillover.
J Neurosci
June 2006
Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
A glial glutamate transporter, GLAST, is expressed abundantly in Bergmann glia and plays a major role in glutamate uptake at the excitatory synapses in cerebellar Purkinje cells (PCs). It has been reported that a higher percentage of PCs in GLAST-deficient mice are multiply innervated by climbing fibers (CFs) than in the wild-type (WT) mice, and that CF-mediated EPSCs with small amplitude and slow rise time, designated as atypical slow CF-EPSCs, are observed in these mice. To clarify the mechanism(s) underlying the generation of these atypical CF-EPSCs, we used (2S,3S)-3-[3-(4-methoxybenzoylamino)benzyloxy]aspartate (PMB-TBOA), an inhibitor of glial glutamate transporters.
View Article and Find Full Text PDFModulation of glutamate mobility reveals the mechanism underlying slow-rising AMPAR EPSCs and the diffusion coefficient in the synaptic cleft.
Neuron
June 2004
Department of Physiology, University College London, Gower Street, London WC1E 6BT, United Kingdom.
Fast- and slow-rising AMPA receptor-mediated EPSCs occur at central synapses. Fast-rising EPSCs are thought to be mediated by rapid local release of glutamate. However, two controversial mechanisms have been proposed to underlie slow-rising EPSCs: prolonged local release of transmitter via a fusion pore, and spillover of transmitter released rapidly from distant sites.
View Article and Find Full Text PDFNon-calyceal excitatory inputs mediate low fidelity synaptic transmission in rat auditory brainstem slices.
Eur J Neurosci
November 2003
Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, UK.
Principal neurons of the medial nucleus of the trapezoid body (MNTB) receive a synaptic input from a single giant calyx terminal that generates a fast-rising, large excitatory postsynaptic current (EPSC), each of which are supra-threshold for postsynaptic action potential generation. Here, we present evidence that MNTB principal neurons receive multiple excitatory synaptic inputs generating slow-rising, small EPSCs that are also capable of triggering postsynaptic action potentials but are of non-calyceal origin. Both calyceal and non-calyceal EPSCs are mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-d-aspartate (NMDA) receptor activation; however, the NMDA receptor-mediated response is proportionally larger at the non-calyceal synapses.
View Article and Find Full Text PDFPhysiology and pharmacology of corticothalamic stimulation-evoked responses in rat somatosensory thalamic neurons in vitro.
J Neurophysiol
May 1997
Department of Neurology, Medical College of Virginia, Richmond 23298-0599, USA.
Whole cell current- and voltage-clamp recording techniques were employed in a rat thalamocortical slice preparation to characterize corticothalamic stimulation-evoked responses in thalamic neurons. Three types of corticothalamic stimulation-evoked responses were observed in thalamic neurons. Of thalamic neurons, 57% responded to corticothalamic stimulation with purely excitatory synaptic responses, whereas 27% had inhibitory synaptic responses and 16% had mixed excitatory/inhibitory responses.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!