Paired‐pulse modulation of fast excitatory synaptic currents in microcultures of rat hippocampal neurons.

Abstract

1. Paired-pulse modulation of excitatory non-N-methyl-D-aspartate (non-NMDA) receptormediated autaptic currents and conventional monosynaptic (interneuronal) excitatory postsynaptic currents (EPSCs) was investigated in microcultures of rat hippocampal neurons, where polysynaptic influences are eliminated. 2. Most autaptic currents and EPSCs exhibited 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 release. 3. Paired-pulse depression and facilitation could be differentially expressed at two distinct postsynaptic targets of a single presynaptic cell, and the form of modulation was not dependent upon the transmitter phenotype of the postsynaptic cell. 4. Paired-pulse depression recovered exponentially with a time constant of -5 s, although in most neurons a much faster component of recovery was detected. Recovery from pairedpulse facilitation was well described by a single exponential 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 frequency immediately following evoked responses. The decay of the frequency 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 presynaptic component to paired-pulse depression. In eight out of nine cells no depression in sEPSC amplitudes was detected following conditioning stimulation. Simultaneously recorded glial glutamate uptake currents showed depression similar to neuronal evoked EPSCs. Finally, NMDA receptormediated EPSC paired-pulse depression at positive potentials was similar to non-NMDA EPSC depression. 7. Neither adenosine nor glutamate feedback onto presynaptic receptors is likely to mediate paired-pulse depression, because neither competitive nor non-competitive inhibitors of the actions of these agents diminished paired-pulse depression.The nervous system relays much of its information via trains of impulses. Because the efficacy of synaptic transmission at many synapses can be altered by the frequency of impulse trains, an understanding of the properties of frequency-dependent modulation of synaptic responses should yield insights into the nature of information processing in the nervous system. Frequency-dependent synaptic modulation in its simplest form has been studied using paired-pulse stimulation protocols. Paired-pulse depression and paired-pulse facilitation, among other forms of short-term modulation, have been well characterized at the vertebrate neuromuscular junction largely because of the simplicity and accessibility of the preparation (del Castillo & Katz, 1954;Takeuchi, 1958

Enhanced Glutamatergic Synaptic Plasticity in the Hippocampal CA1 Field of Food-Restricted Rats: Involvement of CB1 Receptors

“…This idea is supported experimentally by the following two results: (i) the PP ratio of glutamatergic fEPSPs was reduced in FR rats tested during the anticipatory period in comparison with CTRL animals, consistent with an increased probability of presynaptic release of glutamate (Mennerick and Zorumski, 1995), and (ii) recordings of glutamatergic spontaneous mEPSCs in CA1 pyramidal neurons revealed that their frequency was significantly increased in FR animals.…”

“…In order to evaluate whether the observed decrease in CB1R sensitivity to the selective agonist win55,212-2 found in FR rats could result in an altered control of basal glutamate release, we applied the PP protocol on the basis of the observation that changes in PP ratio are indicative of changes in the probability of neurotransmitter release (Mennerick and Zorumski, 1995). In CA1 pyramidal neurons of CTRL animals, the PP ratio had a value of 1.57 ± 0.07, whereas in FR rats that were killed 5 min before food presentation, this value was significantly lower (1.17 ± 0.12, Po0.05); again, the PP ratio detected in FR animals that were tested 360 min after food presentation had a value that was not statistically different from that of CTRL rats (1.67 ± 0.05; Figure 1c and d).…”

Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons

“…In the first set of experiments we examined PPF (at an interpulse interval of 50 msec), a phenomenon whereby a secondary synaptic response is increased by a preceding primary stimulation of equal intensity (23)(24)(25). Changes in PPF are inversely related to transmitter release such that a reduction of PPF is associated with an increased probability of transmitter release (26,27). We found that superfusion of either 44 or 66 mM ethanol significantly decreased PPF of GABA A IPSP͞Cs (relative to the control; P Ͻ 0.05; Fig.…”

Gamma-hydroxybutyrate Reduces GABAA-mediated Inhibitory Postsynaptic Potentials in the CA1 Region of Hippocampus

“…The ratio of the amplitude of the second response to the amplitude of the first inversely correlates with the probability of release, and is therefore usually affected by manipulations that alter release probability (Chieng and Williams 1998;Mennerick and Zorumski 1995) To determine whether GHB reduces GABA A -IPSPs by a postsynaptic reduction in the sensitivity to synaptically released GABA or through a presynaptic depression of GABA release, we initially examined the effects of GHB on the ratio of the amplitudes of GABA A -IPSPs elicited by paired-pulse stimulation (60 msec, interstimulus interval). The amplitude of both the first and the second IPSPs were reduced by GHB (600 M) whereas the paired-pulse ratio was significantly enhanced from 1.22 Ϯ 0.08 to 1.79 Ϯ 0.11 (F 2,5 ϭ 14.8, p Ͻ .01, n ϭ 6) to recover to 1.13 Ϯ 0.10 after 20 min of washout.…”