Kainate receptor-mediated presynaptic inhibition at the mouse hippocampal mossy fibre synapse.
1. The presynaptic action of kainate (KA) receptor activation at the mossy fibre-CA3 synapse was examined using fluorescence measurement of presynaptic Ca2+ influx as well as electrophysiological recordings in mouse hippocampal slices. 2. Bath application of a low concentration (0.2 microM) of KA reversibly increased the amplitude of presynaptic volley evoked by stimulation of mossy fibres to 146 +/- 6 % of control (n = 6), whereas it reduced the field excitatory postsynaptic potential (EPSPs) to 30 +/- 4 %. 3. The potentiating effect of KA on the presynaptic volleys was also observed in Ca2+-free solution, and was partly antagonized by (2S, 4R)-4-methylglutamic acid (SYM 2081, 1 microM), which selectively desensitizes KA receptors. 4. The antidromic population spike of dentate granule cells evoked by stimulation of mossy fibres was increased by application of 0.2 microM KA to 160 +/- 10 % of control (n = 6). Whole-cell current-clamp recordings revealed that the stimulus threshold for generating antidromic spikes recorded from a single granule cell was lowered by KA application. 5. Application of KA (0.2 microM) suppressed presynaptic Ca2+ influx to 78 +/- 4 % of control (n = 6), whereas the amplitude of the presynaptic volley was increased. 6. KA at 0.2 microM reversibly suppressed excitatory postsynaptic currents (EPSCs) evoked by mossy fibre simulation to 38 +/- 9 % of control (n = 5). 7. These results suggest that KA receptor activation enhances the excitability of mossy fibres, probably via axonal depolarization, and reduces action potential-induced Ca2+ influx, thereby inhibiting mossy fibre EPSCs presynaptically. This novel presynaptic inhibitory action of KA at the mossy fibre-CA3 synapse may regulate the excitability of highly interconnected CA3 networks.
Kamiya
H
H
Department of Physiology, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan. hkamiya@akagi.sb.gunma-u.ac.jp
Ozawa
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D002118:Calcium; D007608:Kainic Acid; D018092:Kainic Acid Receptors