Analysis of excitatory synaptic action in pyramidal cells using whole‐cell recording from rat hippocampal slices.

Abstract

SUMMARY1. The pharmacological and biophysical properties of excitatory synapses in the CAI region of the hippocampus were studied using patch electrodes and whole-cell recording from thin slices.2. Excitatory postsynaptic currents (EPSCs) had a fast component whose amplitude was voltage insensitive and a slow component whose amplitude was voltage dependent with a region of negative slope resistance in the range of -70 to -30 mV.3. The voltage-dependent component was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovalerate (APV; 50 /uM), which had no effect on the fast component. Conversely, the fast voltage-insensitive component was abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 (1M) which had no effect on the slow component.4. In Ringer solution with no added Mg2+ the current-voltage relation of the NMDA component was linear over a much larger voltage range than in the presence of 1-3 mM-Mg2+.5. The NMDA component of the EPSC could be switched off with a hyperpolarizing voltage step at the soma. The kinetics of this switch-off was used to estimate the speed of clamp control of the subsynaptic membrane as well as the electrotonic distance from the soma. The kinetic analysis of the EPSC was restricted to synapses which were judged to be under adequate voltage control.6. For those synapses that were close to the soma the time constant for decay for the non-NMDA component, which was voltage insensitive, ranged from 4-8 ms.7. The rise time for the NMDA component was 8-20 ms and the time constant for decay ranged from 60-150 ms.8. During increased transmitter release with post-tetanic potentiation or application of phorbol esters, both components of the EPSC increased to a similar extent.9. These experiments provide a detailed description of the dual receptor mechanism operating at hippocampal excitatory synapses. In addition, the MS 7663 S. HESTRIN AND OTHERS experiments provide an electrophysiological method for estimating the electrotonic distance of synaptic inputs.

Kinetic properties of NMDA receptor‐mediated synaptic currents in rat hippocampal pyramidal cells versus interneurones.

“…From the best fitted functions, the mean value of residual [Mg2+] in nine slices was 14-6 + 3-4 /M (PCs 13-6+441 #M, n = 5; INs 15-9+220 #M, n = 4; difference not significant (Konnerth et al 1990;Keller et al 1991). In contrast to the findings in dentate granule cells, however, and in agreement with results obtained from adult CAI PCs (Hestrin et al 1990a), the time constants of decay were not consistently prolonged by depolarization in the studied cell types.…”

“…Adult CAI PCs, however, ordinarily generate repetitive firing which accommodates during maintained depolarization (Madison & Nicoll, 1984 (Hestrin et al 1990a;Sah, Hestrin & Nicoll, 1990 . These TsS were also identical to the single exponential decay time constants of slow NMDA EPSCs (217-2 + 69 n ms), which therefore were plotted as Ts in Fig.…”

“…Ballanvi & Yaari. 1990;Keller, Konnerth & Yaari, 1991), the decay of NMDA EPSCs in CAI pyramidal cells (PCs) was voltage insensitive (Hestrin, Nicoll, Perkel & Sah. 1990a).…”

Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents

“…NMDA receptor channels have been shown to mediate the slow EPSCs in central neurons (Forsythe and Westbrook, 1988) and non-NMDA receptor channels have been shown to mediate the fast EPSCs (Hestrin et al, 1990). While step applications of glutamate evoke slow decremental current responses from NMDA receptor channels (Ascher et al, 1988;Mayer et al, 1989) similar stimuli evoke rapidly decaying current responses from non-NMDA receptor channels (Kiskin et al, 1986;Tang et al, 1989;Trussell and Fischbach, 1989;Thio et al, 199 1).…”

Depolarization increases the single channel conductance and the open probability of crayfish glutamate channels

“…The voltage sensitivity has been attributed to block by polyamines (Bowie and Mayer, 1995), to voltage dependence of gating Raman and Trussell, 1995), and to voltage dependence of desensitization (Patneau et al, 1993). In other preparations, however, the I-V relation was found to be nearly linear (Hestrin et al, 1990;Keller et al, 1991;Colquhoun et al, 1992;Livsey et al, 1993).…”