PAIRED-PULSE FACILITATION OF IPSCS IN SLICES OF IMMATURE AND MATURE MOUSE SOMATOSENSORY NEOCORTEX

1. Whole cell recordings from layer V neurons of mouse somatosensory cortex were made with the use of a ''blind'' patch-clamp technique. In slices from immature [postnatal days 6 to 11 (P6-P11)] and juvenile (P18-P21) animals, inhibitory postsynaptic currents (IPSCs) were evoked in all cells by extracellular stimulation at the layer V-VI border. Monosynaptic IPSCs, with latency <2 ms, were isolated pharmacologically by blockade of ionotropic glutamatergic transmission. IPSCs were blocked by bicuculline methiodide and reversed near the predicted equilibrium potential for CI-. 2. IPSC characteristics were not different for the two age groups. At 1.5-2 times threshold intensity (0.2 Hz), they fluctuated in amplitude with occasional failures. At -70 or -80 mV, mean amplitudes were -202 +/- 20 (SE) pA and -207 +/- 32 pA for immature (39 cells) and juvenile (13 cells) cortex, respectively. Half rise times were 0.74 +/- 0.03 ms (n = 7 cells) in neonates and 0.67 +/- 0.04 ms (n = 7 cells) in juveniles. Decays were biexponential with tau(1) = 14.8 + 1.3 ms and 7, = 59.0 +/- 7.4 ms (n = 7 cells) in neonates, and tau(1) = 11.9 +/- 1.1 ms and tau(2) = 55.5 +/- 4.2 ms (n = 7 cells) in juveniles. 3. Pairs of stimuli elicited paired-pulse facilitation (PPF) when delivered at brief interstimulus intervals (ISI), and paired-pulse depression (PPD) at long ISI. PPF, which was evident in 64% of immature cells and 38% of juvenile cells, was maximal (38 +/- 4% greater than the conditioning response) at 20-40 ms. PPD, which was evident in 82% of immature cells and 87% of juvenile cells, was maximal (29 +/- 2% smaller than the conditioning response) by 300 ms. In each age group, some animals showed PPF without PPD. 4. In 36% of immature cells and 62% of juvenile cells, the paired-pulse response was characterized by an initial, deep depression followed by rapid return toward the control level by 20-40 ms and subsequent depression with a slower time course typical of PPD. In three of these neurons, the effect of lowering release probability on the early depression was examined by lowering Ca2+ to 0.5 mM and raising Mg2+ to 3.5 mM; in each case the early depression was replaced by PPF. In a different three neurons, two pairs of stimuli were delivered such that the second pair fell during the peak of the late PPD induced by the first pair; in each case, PPF of the second pair was clearly revealed in this way, suggesting a presynaptic mechanism for late PPD. 5. This sequence of early PPF and late PPD may impose a time window for facilitation of IPSCs in neocortex, such that an inhibitory interneuron will be maximally effective when it fires brief (<300 ms) bursts of action potentials at intraburst frequencies >25-50 Hz.