Feed-forward facilitation of glutamate release by presynaptic GABA(A) receptors.
Disynaptic GABAergic inputs from Schaffer collateral (SC) afferents on to the soma of glutamatergic CA1 pyramidal neurons are involved in feed-forward inhibition in the hippocampal neural circuits. Here we report the functional roles of presynaptic GABA(A) receptors on SC afferents projecting to CA1 pyramidal neurons. Muscimol (0.5 microM), a selective GABA(A) receptor agonist, increased SC-evoked EPSC amplitude and decreased paired-pulse ratio in the slice preparation, in addition, it facilitated spontaneous glutamate release on to mechanically dissociated CA1 pyramidal neurons in an external Ca2+-dependent manner. In field recordings, muscimol at low concentrations (< or = 0.5 microM) increased not only the excitability of SC afferents but glutamate release, however, it at high concentrations (> or = 1 microM) changed bidirectionally. These results suggest that the moderate activation of presynaptic GABA(A) receptors depolarizes SC afferents and enhances SC-mediated glutamatergic transmission. When endogenous GABA was disynaptically released by brief trains of stimulation of SC afferents, the axonal excitability in addition to glutamate release was increased. The effects of endogenous GABA on the excitability of SC afferents were blocked by either SR95531 or AMPA receptor blockers, which would be expected to block disynaptic feed-forward neural circuits. The present results provide a novel form of presynaptic modulation (feed-forward facilitation) of glutamatergic transmission by presynaptic GABA(A) receptors within the intrinsic hippocampal neural circuits.
Jang
I-S
IS
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582, Japan.
Ito
Y
Y
Akaike
N
N
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D025461:Feedback, Physiological / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009411:Nerve Endings / Q000378:metabolism / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
D018755:GABA Agonists; D011724:Pyridazines; D011963:Receptors, GABA-A; D017661:Receptors, Presynaptic; D009118:Muscimol; D018698:Glutamic Acid; C049853:gabazine