Journal of Neuroscience, Vol 8, 1632-1644, Copyright © 1988 by Society for Neuroscience
Mechanisms of long-term potentiation: EPSP/spike dissociation, intradendritic recordings, and glutamate sensitivity
JS Taube and PA Schwartzkroin
Department of Physiology, University of Washington, Seattle 98195.
Synaptic efficacy is modified following a brief train of high-frequency
stimulation (HFS) to a cell's afferent fibers (long-term potentiation;
LTP). An alteration in the postsynaptic response to endogenous
neurotransmitter, as a result of an increase in the number of postsynaptic
receptors, has been proposed (Baudry and Lynch, 1980). We tested this
hypothesis in the CA1 hippocampus by intracellularly recording the
postsynaptic response to localized application of glutamate before and
after induction of LTP. When LTP was produced, there was no corresponding
change in neuronal sensitivity to glutamate application. These findings are
not consistent with the hypothesis that HFS of fibers in CA1 stratum
radiatum induces an increase in the number of postsynaptic glutamate
receptors in CA1 pyramidal cells. Previous reports concerning LTP have
indicated a dissociation between the degree of potentiation in the
population EPSP and population spike. Simultaneous recordings of the CA 1
population EPSP and population spike in hippocampal slices confirmed that
the degree of potentiation of the population spike was not predicted by the
degree of potentiation in the population EPSP. Intradendritic impalements
were obtained to more accurately assess changes in the intracellular EPSP
following HFS. When the population EPSP was potentiated, there was also a
potentiated intradendritic EPSP. When the population spike was potentiated
following HFS, however, the intradendritic EPSP was often unchanged; in the
same cell, there was an increased probability of action potential discharge
to stimulation which was originally (i.e., pre-HFS) subthreshold for spike
initiation. These results indicate that the EPSP (intracellular or
extracellular) may be potentiated following HFS, but this potentiation is
not a prerequisite for, or a correlation of, potentiation in the population
spike. Furthermore, these findings suggest that LTP is composed of 2
independent components--a synaptic component and an EPSP-to-spike coupling
component.