Attenuated Plasticity of Postsynaptic Kainate Receptors in Hippocampal CA3 Pyramidal Neurons

Abstract

Kainate receptor-mediated components of postsynaptic currents at hippocampal mossy fiber synapses have markedly slower kinetics than currents arising from AMPA receptors. Here, we demonstrate that other aspects of kainate and AMPA receptor function at this synapse are distinct; in particular, kainate receptor currents are less sensitive to short-and long-term increases in presynaptic strength. EPSCs arising predominantly from AMPA receptors exhibited well characterized paired-pulse facilitation, frequency facilitation, and NMDA receptor-independent long-term potentiation, whereas isolated kainate receptor synaptic currents (KA-EPSCs) exhibited attenuated facilitation and long-term potentiation. In addition, KA-EPSCs varied in their sensitivity to a low-affinity competitive antagonist, suggestive of a synaptic heterogeneity greater than that of EPSCs comprised predominantly of AMPA receptors. These data suggest that the proportional contribution of AMPA and kainate receptors to ensemble synaptic currents will vary depending on the firing frequency of mossy fiber afferents. These synaptic features may be a mechanism for limiting activation of kainate receptors at mossy fiber synapses, which has been shown to be involved in seizurogenic firing of the CA3 network.

Short-Term Plasticity of Kainate Receptor-Mediated EPSCs Induced by NMDA Receptors at Hippocampal Mossy Fiber Synapses

“…Thus, at this membrane potential in the presence of GYKI 53655, Mf-EPSCs are in great part mediated by KARs. In response to a train of five pulses at 20 Hz, the amplitude of KAREPSCs during the train increased and remained potentiated 500 ms after the train because of presynaptic facilitation (Salin et al, 1996;Ito et al, 2004) (Fig. 1 A).…”

“…Nevertheless, short-term depression of KAR-EPSCs in conditions of high afferent activity leading to spike discharge is expected to exert a feedback inhibition on the sustained depolarization induced by KAR-EPSPs. Interestingly, it was reported that KAR-EPSCs show attenuated forms of presynaptic plasticity compared with AMPAR-EPSCs (Ito et al, 2004). Both mechanisms will concur in preventing the overactivation of synaptic KARs under conditions of sustained network activity and might thus favor information processing in conditions of short bursts of afferent stimulation.…”

“…In these neurons, a train of 200 stimuli at 5 Hz results in long-term depression of KAR-EPSCs via a mechanism involving mGluR5, PKC, and PICK1 (protein interacting with C kinase-1) PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain interactions (Park et al, 2006), and possibly a change in the number of synaptic KARs . At hippocampal mossy fiber synapses, KAR-EPSCs are regulated as a consequence of presynaptic changes in glutamate release properties (Ito et al, 2004), but no form of synaptic plasticity specific for KAR-EPSCs has yet been described. However, the functional properties of recombinant KARs can be regulated on a shorter time scale by direct cAMP-dependent phosphorylation (Traynelis and Wahl, 1997).…”

Divergent Pharmacological Activity of Novel Marine-Derived Excitatory Amino Acids on Glutamate Receptors

“…Horizontal hippocampal slices (0.35 m) were made from P30 to P40 129SvEv mice as described previously (Ito et al, 2004). Whole cell patch-clamp recordings of AMPA-excitatory postsynaptic currents (AMPA-EPSCs) were made from CA1 pyramidal cells while stimulating Schaffer collateral inputs with a monopolar glass electrode in the stratum radiatum.…”

The Effect of Subacute Supplementation of Taurine on Spatial Learning and Memory

“…Recent electrophysiological studies using rat brain preparations, however, have shown that taurine application induced long-lasting synaptic potentiation [3,6]. The features of this taurine-induced synaptic potentiation are similar to those of long-term potentiation (LTP) [4,19], which is a typical example of synaptic plasticity, and is thought to be a basic model for learning and memory [8], indicating that taurine is likely to be involved in learning and memory. Despite accumulation of findings on the relationship between taurine and synaptic plasticity by electrophysiological studies, the effect of taurine on learning and memory at the behavior level is complicated.…”