Postsynaptic kainate receptors (KARs) have been found in the CNS along with AMPA receptors (AMPARs), but because KARmediated EPSCs are much smaller and slower than AMPARmediated EPSCs, it remains unclear whether these postsynaptic KARs are functionally significant. In this study we measured KAR-and AMPAR-mediated EPSPs in hippocampal interneurons, and then we used these EPSPs in a model to examine the effects of afferent firing on each receptor. In this model the KARs generated a large tonic depolarization when activated by a small population of afferent fibers firing asynchronously at physiologically relevant firing rates (1-5 Hz). At 3-5 Hz this tonic depolarization exceeded the peak depolarization mediated by AMPARs in response to the same afferent activity. We also found that, unlike AMPARs, KARs did not generate large oscillations in membrane potential during theta rhythms. When simulated EPSCs were injected into interneurons to mimic afferents firing at 5 Hz, we found that currents simulating KARs elicited more spiking than currents simulating AMPARs. We also found that simulated AMPARs, but not KARs, could transmit presynaptic theta rhythms into postsynaptic spiking at the theta rhythm. Our results suggest that synaptically activated KARs have a strong influence on membrane potential and that AMPARs and KARs differ in their ability to encode temporal information.

Presynaptic inhibition is a form of neuromodulation that interacts with activity-dependent short-term plasticity so that the magnitude, and sometimes even the polarity, of that activity-dependent short-term plasticity is changed. However, the functional consequences of this interaction during physiologically relevant spike trains are poorly understood. We examined the effects of presynaptic inhibition on excitatory synaptic transmission during physiologically relevant spike trains, using the GABA(B) receptor (GABA(B)R) agonist baclofen to engage presynaptic inhibition and field EPSPs (fEPSPs) in hippocampal slices to monitor synaptic output. We examined the effects of baclofen on the relationship between an fEPSP during the spike train and the timing of spikes preceding that fEPSP, a relationship that we refer to as the history dependence of synaptic transmission. Baclofen alters this history dependence by causing no inhibition during short interspike intervals (ISIs) in the spike train but a maximal inhibition during long ISIs. This effect strengthens the dependence of the fEPSP on the first ISI preceding it. One consequence of this effect is that the apparent affinity of baclofen is strongly reduced during physiologically relevant spike trains when compared with conventional stimulus paradigms, and a second consequence is that the overall inhibition experienced by a synapse will vary considerably during repeated trials of a behavioral task. We conclude that GABA(B)R-mediated presynaptic inhibition is more accurately described as a high-pass filter than as a simple inhibition, and that this filtering must be taken into account to accurately assess the effects of presynaptic inhibition under physiologically relevant conditions.

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Presynaptic inhibition is a widespread mechanism for regulating transmitter release in the CNS. Presynaptic inhibitors act as a high-pass filter, but the functional consequence of this filtering during the synaptic processing of behaviorally relevant activity remains unknown. Here we use analytical approaches to examine the effects of presynaptic inhibition on synaptic output in response to activity patterns from CA3 pyramidal cells during the performance of a complex behavioral task. We calculate that presynaptic inhibition enhances the contrast between background activity and responses to environmental cues and that neuronal responses to location are subject to stronger contrast enhancement than neuronal responses to olfactory information. Our analysis suggests that presynaptic inhibition also enhances the importance of integrative inputs that respond to many behavioral cues during the task at the expense of specific inputs that respond to only a few of these cues.

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