Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and...

Paired-pulse plasticity is typically used to study the mechanisms underlying synaptic transmission and modulation. An important question relates to whether, under physiological conditions in which various opposing synaptic properties are acting in parallel, the net effect is facilitatory or depressive, that is, whether cells further or closer to threshold. For example, does the net sum of paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs), paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and the hyperpolarizing slow IPSP result in depression or facilitation? Here we examine how different time-dependent properties act in parallel and examine the contribution of gamma-aminobutyric acid-B (GABAB) receptors that mediate two opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons, we examined the postsynaptic responses to paired-pulse stimulation (with intervals between 50 and 400 ms) of the Schaffer collaterals and white matter, respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each EPSP were analyzed before and after application of the GABAB antagonist CGP-55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was generally depressed (further from threshold) compared with the first at the longer intervals; however, these EPSPs were generally broader and exhibited a longer TTP that could result in facilitation by enhancing temporal summation. At the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude in the absence and presence of CGP-55845. In contrast, on average L-II/III cells did not exhibit facilitation at any interval, in the absence or presence of CGP-55845. CGP-55845 generally "erased" short-term plasticity, equalizing the peak amplitude and TTP of the first and second EPSPs at longer intervals in the hippocampus and auditory cortex. These results show that it is necessary to consider all time-dependent properties to determine whether facilitation or depression will dominate under intact pharmacological conditions. Furthermore our results suggest that GABAB-dependent properties may be the major contributor to short-term plasticity on the time scale of a few hundred milliseconds and are consistent with the hypothesis that the balance of different time-dependent processes can modulate the state of networks in a complex manner and could contribute to the generation of temporally sensitive neural responses.