DIFFERENTIAL ONTOGENY OF PRESYNAPTIC AND POSTSYNAPTIC GABA(B) INHIBITION IN RAT SOMATOSENSORY CORTEX

1. The postnatal maturation of gamma-aminobutyric acid (GABA)B recepto r-mediated presynaptic inhibition was studied in brain slices of rat s omatosensory cortex maintained in vitro. Patchclamp techniques were us ed to record whole-cell inhibitory postsynaptic currents from layer II -III neurons in animals from postnatal days (P) 7-24. Monosynaptic inh ibitory postsynaptic currents (IPSCs) were evoked after N-methyl-D-asp artate (NMDA) and non-NMDA type glutamate receptors had been blocked b y D-amino-phosphonovaleric acid (D-AP5, 20 muM) and 6-cyano-7-nitroqui noxaline-2,3-dione (CNQX, 10 muM), respectively. These IPSCs were sole ly mediated by postsynaptic GABA(A) receptors because they were abolis hed by bicuculline (10 muM), reversed polarity near the chloride equil ibrium potential, and were recorded with electrodes that contained Cs to block postsynaptic GABA(B) responses. 2. When pairs of stimuli sep arated by intervals of 0.1-10s were used to evoke IPSCs, the second re sponse was depressed, an effect that was maximal at 300 ms. Evoked IPS Cs were also depressed by baclofen (10 muM). The paired pulse depressi on (PPD) of monosynaptic IPSCs was decreased or eliminated by 2-OH-sac lofen (200 muM). These findings indicate that PPD of monosynaptic IPSC s was due to presynaptic GABA(B) receptor-mediated inhibition of GABA release. 3. There were no significant differences in the amounts of PP D in neurons from different age groups (P7-10, P12-17, P22-24) at any interstimulus interval tested (0.1-10 s). 4. In neurons that were perf used with pipette solutions that contained K+, the short latency GABA( B) receptor-mediated current (fast IPSC) was occasionally followed by a slow outward current that was blocked by 2-OH-saclofen. These GABA(B ) receptor-mediated slow IPSCs were observed in 5 of 12 neurons from t he P22-24 age group, but only 2 of 23 and 3 of 15 neurons from the P7- 10 and P12-17 groups, respectively. 5. These results suggest that GABA (B) receptor-mediated presynaptic inhibition of stimulus-evoked GABA r elease is already present by P7, as is the postsynaptic GABA(A) recept or-mediated fast IPSC, whereas the postsynaptic GABA(B) receptor-media ted slow IPSC becomes functionally active somewhat later. The early on togenesis of presynaptic GABA(B) autoinhibition coupled with the delay ed development of postsynaptic GABA(B) IPSCs might play an important r ole in the development and plasticity of immature cortex.