Voltage-clamp analysis of posttetanic potentiation of the mossy fiber to CA3 synapse in hippocampus.
1. Short-term changes in synaptic efficacy were studied at the mossy fiber (MF) to CA3 (MF-CA3) synapse in the in vitro hippocampus. Monosynaptic excitatory postsynaptic currents (EPSCs) were recorded before and during posttetanic potentiation (PTP) with the use of intracellular recording and single-electrode voltage-clamp (SEVC) techniques. 2. Repetitive stimulation (100 Hz for 1 s) of the MF synaptic inputs to CA3 pyramidal cells resulted in PTP averaging 170 +/- 19% (SE, n = 42) over control and decaying with a time constant (tau p) of 59.7 +/- 5 s(n = 23). Reproducible episodes of PTP could be recorded if low stimulus intensities were used. Also, after MF tetanization, a faster component, termed augmentation, preceded PTP but could not be accurately resolved within the experimental protocol; only estimates of this component are included. 3. Biophysical parameters of the EPSC that were monitored before and during PTP included synaptic conductance (G), synaptic reversal potential (Erev), decay time constant (tau EPSC), and input resistance of the postsynaptic cell. During PTP the EPSC synaptic conductance increased from 9.8 to 32.7 nS (P less than 0.02, n = 6), whereas there was no statistical change in Erev (-6.0 compared with -6.7 mV, n = 6), tau EPSC (4.3 compared with 4.5 ms, n = 9), or postsynaptic input resistance (59 compared with 63 M omega, n = 12). 4. A presynaptic contribution to PTP was studied directly by observing changes in transmitter release during PTP. Presynaptic mechanisms were assessed by determining the ratio of evoked synaptic excitatory postsynaptic potentials (EPSPs) over the total number of stimuli (EPSP-to-stimuli ratio). The ratio of EPSP to stimuli changed from 0.64 to 0.90 (P less than 0.01, n = 7) during PTP. A reduction in the number of synaptic failures can only be explained by a presynaptic mechanism. No assumptions concerning the statistical distribution of transmitter release were necessary because no statistical parameters were determined. 5. Changes in postsynaptic cell properties do not appear to contribute to PTP studied under the present experimental conditions. Direct stimulation of the postsynaptic neuron via the intracellular recording electrode (20-100 Hz/1 s) failed to produce potentiation of the EPSC; in fact, a slight depression was observed at 50 and 100 Hz direct stimulation. Likewise, the postsynaptic input resistance and synaptic Erev did not change during PTP. 6. The specific N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (APV, 20 microM) had no effect on either the magnitude or duration of PTP.(ABSTRACT TRUNCATED AT 400 WORDS)
Griffith
W H
WH
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University, College Station 77843.
D000200:Action Potentials; D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter