DIFFERENT MECHANISMS REGULATE IPSC KINETICS IN EARLY POSTNATAL AND JUVENILE HIPPOCAMPAL GRANULE CELLS

1. Monosynaptic inhibitory postsynaptic currents (IPSCs) were recorded from early postnatal and juvenile dentate granule cells in rat brain slices at room temperature. The focally evoked currents were mediated by gamma-aminobutyric acid-a (GABA(A)) receptors. 2. IPSCs were charac terized by a steep rising phase and a slower, monoexponential decay ti me course. The decay time constant was potential dependent and average values ranged from 33 ms at a holding potential of -60 mV to 58 ms at a holding potential of +40 mV. 3. IPSCs were studied in tissue from a nimals between postnatal day (p) 3 and p25. All kinetic parameters as well as the mean current amplitude were unchanged during this ontogene tic period. 4. In juvenile granule cells from animals aged 13-16 days, addition of the GABA uptake blocker (R)-N-[4,4-bis (3-methyl-2-thieny l)but-3-enl-yl] nipecotic acid (tiagabine) (10 mu M) prolonged the dec aying phase of the IPSCs. The current decay remained monoexponential b ut the time constant increased to 250% of control values. Mean current amplitudes remained largely unchanged. 5. In contrast, tiagabine had no effect on IPSCs in early postnatal tissue. The decay time constant remained unchanged in cells recorded from animals aged p4-p6. Other up take blockers were also ineffective during the first postnatal week, w hereas beta-alanine, NNC-711, and L-2,3-diaminoproprionic acid enhance d the decay time constant in the older tissue (p13-p16). 6. Hypoosmola ric extracellular solution was applied to restrict the extracellular s pace. In juvenile tissue (p13-p16), IPSCs were not affected by this tr eatment, whereas early postnatal granule cells (p4-p6) displayed clear ly prolonged IPSC decay time constants (165% of control). 7. We conclu de that the mechanism governing the kinetics of evoked IPSCs in granul e cells changes during ontogenesis. Whereas in early postnatal tissue the transmitter leaves the postsynaptic site by diffusion, GABA uptake becomes time limiting after 2 wk of postnatal development.