The GABAergic projection of the dentate gyrus to hippocampal area CA3 of the rat: pre- and postsynaptic actions after seizures.
The glutamatergic granule cells of the dentate gyrus transiently express GABAergic markers after seizures. Here we show that when this occurs, their activation produces (i) GABA(A) receptor-mediated synaptic field responses in CA3, with the physiological and pharmacological characteristics of mossy fibre transmission, and (ii) GABA(A) receptor-mediated collateral inhibition. Control hippocampal slices present, on stimulation of the dentate gyrus, population responses in stratum lucidum, which are blocked by ionotropic glutamate receptor antagonists. By contrast, in slices from rats subjected to seizures in vivo, dentate activation additionally produces GABA(A) receptor-mediated field synaptic responses in the presence of glutamate receptor antagonists. One-dimensional current source density analysis confirmed the spatial coincidence of the glutamatergic and GABAergic dendritic currents. The GABA(A) receptor-mediated field responses show frequency-dependent facilitation and strong inhibition during activation of metabotropic glutamate receptors. In the presence of glutamate receptor blockers, a conditioning pulse delivered to one site of the dentate gyrus inhibits the population synaptic response and the afferent volley provoked by the activation of a second site, in a bicuculline-sensitive manner. In accordance with this, antidromic responses evoked by mossy fibre activation were enhanced by perfusion of bicuculline. Our results suggest that, for GABA receptor-dependent field potentials to be detected, a considerable number of boutons of a well-defined GABAergic pathway should simultaneously release GABA to act on a large number of receptors. Therefore, putative GABA release from the mossy fibres acts on pre- and postsynaptic sites to affect hippocampal activity at the network level after seizures.
Department of Physiology, Biophysics and Neuroscience, Centro de Investigación y Estudios Avanzados, Mexico.
Mario
M
Treviño
Rafael
R
Gutiérrez
D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D005680:gamma-Aminobutyric Acid