KINETIC-PROPERTIES OF NMDA RECEPTOR-MEDIATED SYNAPTIC CURRENTS IN RAT HIPPOCAMPAL PYRAMIDAL CELLS VERSUS INTERNEURONS

1. Whole-cell tight-seal recordings were obtained from visually identified pyramidal cells (PCs) and interneurones (INs) in the CA1 field of thin hippocampal slices from 13- to 23-day-old rats. The INs sampled were classified according to their location either in the molecular layer (M-INs) or in the oriens layer and alveus (OA-INs). PCs and INs differed in their mode of firing when depolarized by a prolonged current pulse. Whereas PCs fired a single action potential, most INs responded with non-accommodating high frequency spike firing. 2. In the presence of 1 mum tetrodotoxin (TTX), bath application of either 50 mum L-glutamate with 10 mum 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or 2.5 mum N-methyl-D-aspartate (NMDA), induced a similar conductance increase in PCs and INs that was completely blocked by 200 muM DL-2-amino-5-phosphonovaleric acid (APV). The NMDA receptor-mediated currents reversed around 4 mV and exhibited an area of negative slope conductance at potentials more negative than - 20 to - 30 mV in the presence of 1-2 mm Mg2+. 3. Dual-component excitatory postsynaptic currents (EPSCs) were evoked in PCs and INs by stimulating afferent fibres close to the neurone. The NMDA receptor-mediated component of the EPSCs (NMDA EPSC) was isolated by adding 10 mum CNQX to block non-NMDA receptors. The NMDA EPSCs in all cell types reversed around 1.5 mV and were abolished by 50 mum APV. 4. In saline containing 1 mm Mg2+, the peak current-voltage (I-V) relationship of NMDA EPSCs in PCs and INs showed an area of negative slope conductance at voltages more negative than - 20 to - 30 mV. In nominally Mg2+-free saline, the peak I-V relation was linear over a much wider voltage range in both cell types. 5. The 10-90 % rise times of NMDA EPSCs at - 60 mV ranged from 4.5 to 16 ms in PCs (mean 8.7 ms; n = 25) and in M-INs (mean 9.1 ms; n = 10). Their decay could be best fitted with the sum of two exponentials. The decay of NMDA EPSCs in PCs was significantly slower than that recorded in INs. The average fast (tau(f)) and slow (tau(s)) time constants of decay were, respectively, 66.5 and 353.9 ms in PCs, and 34.4 and 212.5 ms in M-INs. The corresponding mean fast (A(f)) and slow (A(s)) current amplitude components of the NMDA EPSCs were - 96.8 and - 86.8 pA in PCs, and - 43 and - 96.8 pA in M-INs. 6. The time course of NMDA EPSCs in OA-INs (n = 37) was considerably more variable. In 18.9% of the cells the rise times were in the ordinary range (4.5-10 ms; mean 6-9 ms) and the decay was biexponential (mean tau(f) and tau(s), 49 and 212 ms; mean A(f) and A(s), - 76.3 and - 137.2 pA, respectively). In 73 % of OA-INs the rise times were very slow (18-53 ms; mean 31.2 ms) and decayed monoexponentially (mean time constant 217.2 ms). The remaining 8% had rise times in the ordinary range (10-14 ms; mean 11.7 ms) but decayed as a single exponential (mean time constant 226 ms). 7. Changes in holding voltage had no systematic effect on rise time and decay of ordinary and slow NMDA EPSCs. 8. Neither changing the site of stimulation, nor modulating the amount of glutamate release by varying stimulus intensity, lowering extracellular Ca2+ or adding Cd 2+ to the saline, affected the rise time or the decay of slow NMDA EPSCs. 9. We conclude that PCs and INs in area CA1 of the rat hippocampus express NMDA EPSCs with different kinetic characteristics. NMDA EPSCs in the majority of OA-INs display unusually slow rise times.