AMPA Receptors and Kainate Receptors Encode Different Features of Afferent Activity

Abstract

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.

KRIP6: A novel BTB/kelch protein regulating function of kainate receptors

“…High levels of KRIP6 might protect neurons during high frequency release of glutamate by inhibiting kainate receptor-mediated peak current, reducing postsynaptic depolarization and excessive divalent influx. High levels of KRIP6 might also favor elevated steady-state kainate responses, increasing input temporal summation (Frerking and Ohliger-Frerking, 2002) or affect kainate-induced gamma oscillations and epileptiform bursts (Fisahn et al, 2004).…”

Differential contribution of kainate receptors to excitatory postsynaptic currents in superficial layer neurons of the rat medial entorhinal cortex

“…For instance, the slow decay kinetics of KAR EPSCs results in a total charge transfer similar to that of AMPA EPSCs in CA1 interneurons (Frerking et al, 1998). Furthermore, the slow decay kinetics of KARs appear to mediate a large influence on membrane potential due to summation of EPSCs at physiologically relevant firing rates (Frerking and Ohliger-Frerking, 2002). This temporal summation of KAR mediated EPSCs may also play a role in the generation and maintenance of slow wave oscillations in layer III pyramidal neurons of the mEC (Cunningham et al, 2006).…”

“…These receptors have been shown to both mediate and modulate synaptic transmission in both the central and peripheral nervous system (for reviews see (Chittajallu et al, 1999, Frerking and Nicoll, 2000, Lerma et al, 2001, Lerma, 2003, Lerma, 2006, Pinheiro and Mulle, 2006). Regarding the mediation of synaptic transmission, functional postsynaptic KARs have been demonstrated in a variety of cell types (Castillo et al, 1997, Vignes and Collingridge, 1997, Cossart et al, 1998, Frerking et al, 1998, DeVries and Schwartz, 1999, Kidd and Isaac, 1999, Li et al, 1999, Bureau et al, 2000, Cossart et al, 2002, Ali, 2003, Eder et al, 2003, Vitten et al, 2004, Wu et al, 2005, Jin et al, 2006 and may impose unique integrative properties to neurons (Frerking and Ohliger-Frerking, 2002). Furthermore, the expression of postsynaptic KARs has been shown to be restricted in a cellular and subcellular manner.…”

Neuronal metabolism governs cortical network response state

“…Such bistable behavior is thought to depend on a balance of recurrent excitation and local inhibition (12,13) in addition to slow-wave input from the thalamus (14). However, persistent depolarized states might also occur through synaptic excitation alone, with kinetically slow excitatory synaptic potentials (EPSPs) such as those generated by kainate receptors (15) or NMDA receptors (but see below), temporally summating with sufficient background activity (16). In addition, such a maintained depolarization can be generated purely by intrinsic ionic currents in bistable neurons (17).…”