Ontogenesis of presynaptic GABAB receptor-mediated inhibition in the CA3 region of the Rat Hippocampus. Olivier Caillard, Heather A. McLean, Yehezkel Ben-Ari & Jean-Luc Gaúarsa. INSERM U29, Hospital de Port-Royal, 123 Bd. de Port-Royal, 75014 Paris, France.
APStracts 4:310N, 1997.
ABSTRACT
[gamma]_-aminobutyric acid-B (GABA_B_) receptor-dependent and -independent components of paired-pulse depression (PPD) were investigated in the rat CA3 hippocampal region. Intracellular and whole-cell recordings of CA3 pyramidal neurones were performed on hippocampal slices obtained from neonatal (5-7 day old) and adult (27-34 day old) rats. Electrical stimulation in the hilus evoked monosynaptic GABA_A_ postsynaptic currents (eIPSCs) isolated in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7- nitroquinoxaline-2,3-dione (CNQX, 10æM) and D(-)2-amino-5-phosphovaleric acid (D-AP5, 50æM) with QX314 filled electrodes. In adult CA3 pyramidal neurones, when a pair of identical stimuli was applied at interstimulus intervals (ISIs) ranging from 50 to 1500ms the amplitude of the second eIPSC was depressed when compared with the first eIPSC. This paired-pulse depression (PPD) was partially blocked by P-3-aminopropyl-P-diethoxymethyl phosphoric acid (CGP35348, 0.5mM), a selective GABA_B_ receptor antagonist. In neonates, PPD was restricted to ISIs shorter than 200 ms and was not affected by CGP35348. The GABA_B_ receptor agonist baclofen reduced the amplitude of eIPSCs in a dose-dependent manner with the same efficiency in both adults and neonates. Increasing the probability of transmitter release with high Ca_2+ _(4mM) / low Mg_2+_ (0.3mM) external solution revealed PPD in neonatal CA3 pyramidal neurones that was (i) partially prevented by CGP35348, (ii) independent of the membrane holding potential of the recorded cell and (iii) independent of the reversal potential of GABA_A_ eIPSCs. In adults the GABA uptake blocker tiagabine (20æM) increased the duration of eIPSCs and the magnitude of GABA_B_ receptor-dependent PPD. In neonates, tiagabine also increased duration of eIPSCs but to a lesser extent than in adult, and did not reveal a GABA_B_ receptor-dependent PPD. These results demonstrate that while GABA_B_ receptor- dependent and -independent mechanisms of presynaptic inhibition are present on GABAergic terminals and functional, they do not operate at the level of monosynaptic GABAergic synaptic transmission at early stages of development. Absence of presynaptic autoinhibition of GABA release seems to be due to the small amount of transmitter that can access presynaptic regulatory sites. 

Received 16 July 1997; accepted in final form 5 November1997.
APS Manuscript Number J593-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997