S. Mennerick et Cf. Zorumski, PAIRED-PULSE MODULATION OF FAST EXCITATORY SYNAPTIC CURRENTS IN MICROCULTURES OF RAT HIPPOCAMPAL-NEURONS, Journal of physiology, 488(1), 1995, pp. 85-101
1. Paired-pulse modulation of excitatory non-N-methyl-D-aspartate (non
-NMDA) receptor-mediated autaptic currents and conventional monosynapt
ic (interneuronal) excitatory postsynaptic currents (EPSCs) was invest
igated in microcultures of rat hippocampal neurons, where polysynaptic
influences are eliminated. 2. Most autaptic currents and EPSCs exhibi
ted paired-pulse depression in response to paired stimuli. Depression
was sensitive to the level of transmitter release, which was varied by
manipulating extracellular Ca2+ and Mg2+ concentrations. Paired-pulse
facilitation emerged in many cells at low levels of transmitter relea
se. 3. Paired-pulse depression and facilitation could be differentiall
y expressed at two distinct postsynaptic targets of a single presynapt
ic cell, and the form of modulation was not dependent upon the transmi
tter phenotype of the postsynaptic cell. 4. Paired-pulse depression re
covered exponentially with a time constant of similar to 5 s, although
in most neurons a much faster component of recovery was detected. Rec
overy from paired-pulse facilitation was well described by a single ex
ponential of 380 +/- 57 ms. 5. Under conditions of robust paired-pulse
depression of evoked responses, spontaneous autaptic and postsynaptic
currents (sEPSCs, presumed miniature EPSCs) occurred at an enhanced f
requency immediately following evoked responses. The decay of the freq
uency increase mirrored the time course of recovery from paired-pulse
facilitation of evoked responses examined under conditions of reduced
transmitter release. 6. Several lines of evidence suggested a large pr
esynaptic component to paired-pulse depression. In eight out of nine c
ells no depression in sEPSC amplitudes was detected following conditio
ning stimulation. Simultaneously recorded glial glutamate uptake curre
nts showed depression similar to neuronal evoked EPSCs. Finally, NMDA
receptor mediated EPSC paired-pulse depression at positive potentials
was similar to non-NMDA EPSC depression. 7. Neither adenosine nor glut
amate feedback onto presynaptic receptors is likely to mediate paired-
pulse depression, because neither competitive nor non-competitive inhi
bitors of the actions of these agents diminished paired-pulse depressi
on.