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Do mossy fibers release GABA?

Walker, MC; Ruiz, A; Kullmann, DM; (2002) Do mossy fibers release GABA? EPILEPSIA , 43 196 - 202.

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Abstract

Purpose: Mossy fibers are the sole excitatory projection from dentate gyrus granule cells to the hippocampus, forming part of the trisynaptic hippocampal circuit. They undergo signficiant plasticity during epileptogenesis and have been implicated in seizure generation. Mossy fibers are a highly unusual projection in the mammalian brain; in addition to glutamate, they release adenosine, dynorphin, zinc, and possibly other peptides. Mossy fiber terminals also show intense immunoreactivity for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and immunoreactivity for GAD67. The purpose of this review is to present physiologic evidence of GABA release by mossy fibers and its modulation by epileptic activity.Methods: We used hippocampal slices from 3- to 5-week-old guinea pigs and made whole-cell voltage clamp recordings from CA3 pyramidal cells. We placed stimulating electrodes in stratum granulosum and adjusted their position in order to recruit mossy fiber to CA3 projections.Results: We have shown that electrical stimuli that recruit dentate granule cells elicit monosynaptic GABA(A) receptor-mediated synaptic signals in CA3 pyramidal neurons. These inhibitory signals satisfy the criteria that distinguish mossy fiber-CA3 synapses: high sensitivity to metabotropic glutamate-receptor agonists, facilitation during repetitive stimulation, and N-methyl-D-aspartate (NMDA) receptor-independent long-term potentiation.Conclusions: We have thus provided compelling evidence that there is a mossy fiber GABAergic signal. The physiologic role of this mossy fiber GABAergic signal is uncertain, but may be of developmental importance. Other evidence suggests that this GABAergic signal is transiently upregulated after seizures. This could have an inhibitory or disinhibitory effect, and further work is needed to elucidate its actual role.

Type: Article
Title: Do mossy fibers release GABA?
Location: FOZ DO IGUACU, BRAZIL
Keywords: mossy fibers, GABA, epilepsy, hippocampus, LONG-TERM POTENTIATION, HIPPOCAMPAL DENTATE GYRUS, RAT HIPPOCAMPUS, GLUTAMATE-DECARBOXYLASE, GRANULE CELLS, GUINEA-PIG, RECEPTOR SUBUNITS, 2 FORMS, SYNAPSES, INHIBITION
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy
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 > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/134440
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