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

1. The postnatal maturation of gamma-aminobutyric acid (GABA)B receptor-mediated presynaptic inhibition was studied in brain slices of rat somatosensory cortex maintained in vitro. Patchclamp techniques were used to record whole-cell inhibitory postsynaptic currents from layer II-III neurons in animals from postnatal days (P) 7-24. Monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked after N-methyl-D-aspartate (NMDA) and non-NMDA type glutamate receptors had been blocked by D-amino-phosphonovaleric acid (D-AP5, 20 muM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 muM), respectively. These IPSCs were solely mediated by postsynaptic GABA(A) receptors because they were abolished by bicuculline (10 muM), reversed polarity near the chloride equilibrium potential, and were recorded with electrodes that contained Cs+ to block postsynaptic GABA(B) responses. 2. When pairs of stimuli separated by intervals of 0.1-10s were used to evoke IPSCs, the second response was depressed, an effect that was maximal at 300 ms. Evoked IPSCs were also depressed by baclofen (10 muM). The paired pulse depression (PPD) of monosynaptic IPSCs was decreased or eliminated by 2-OH-saclofen (200 muM). These findings indicate that PPD of monosynaptic IPSCs was due to presynaptic GABA(B) receptor-mediated inhibition of GABA release. 3. There were no significant differences in the amounts of PPD 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 perfused 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 the 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 release is already present by P7, as is the postsynaptic GABA(A) receptor-mediated fast IPSC, whereas the postsynaptic GABA(B) receptor-mediated slow IPSC becomes functionally active somewhat later. The early ontogenesis of presynaptic GABA(B) autoinhibition coupled with the delayed development of postsynaptic GABA(B) IPSCs might play an important role in the development and plasticity of immature cortex.