Quantal Release of Glutamate Generates Pure Kainate and Mixed AMPA/Kainate EPSCs in Hippocampal Neurons

Abstract

The relative contribution of kainate receptors to ongoing glutamatergic activity is at present unknown. We report the presence of spontaneous, miniature, and minimal stimulation-evoked excitatory postsynaptic currents (EPSCs) that are mediated solely by kainate receptors (EPSC(kainate)) or by both AMPA and kainate receptors (EPSC(AMPA/kainate)). EPSC(kainate) and EPSC(AMPA/kainate) are selectively enriched in CA1 interneurons and mossy fibers synapses of CA3 pyramidal neurons, respectively. In CA1 interneurons, the decay time constant of EPSC(kainate) (circa 10 ms) is comparable to values obtained in heterologous expression systems. In both hippocampal neurons, the quantal release of glutamate generates kainate receptor-mediated EPSCs that provide as much as half of the total glutamatergic current. Kainate receptors are, therefore, key players of the ongoing glutamatergic transmission in the hippocampus.

Use-dependent amplification of presynaptic Ca 2+ signaling by axonal ryanodine receptors at the hippocampal mossy fiber synapse

“…Among excitatory synapses onto CA3 neurons, only mossy fiber synapses express postsynaptic kainate receptors (26,27). Therefore, the slow mEPSC KA recorded in the presence of GYKI 53655 reflects quantal release solely from the mossy fiber terminals (28). Application of 10 mM caffeine significantly increased the frequency (to 369 Ϯ 155% of control, n ϭ 5), but not the amplitude (to 109 Ϯ 2%), of the mEPSC KA recorded in the presence of GYKI 53655 ( Fig.…”

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

“…In this case, we used 1 μM NBQX, which has been reported to have a higher affinity at this concentration for AMPA receptors over KAR receptors (Wilding and Huettner, 1996, Bureau et al, 1999, Cossart et al, 2002, Epsztein et al, 2005. Representative recordings of non-NMDA EPSCs, both before and after adding 1 μM NBQX, from S an NS neurons, are shown in Figure 5A.…”

“…Although not universally present, functional postsynaptic KARs have been shown to be present in a variety of cell types such as cerebellar granule cells and Golgi cells (Bureau et al, 2000), retinal bipolar cells (DeVries and Schwartz, 1999), neurons of the superficial dorsal horn (Li et al, 1999), lateral superior olive (Vitten et al, 2004), motor & somatosensory cortex (Kidd and Isaac, 1999, Ali, 2003, Eder et al, 2003, the amygdala , the anterior cingulate cortex (Wu et al, 2005), the globus pallidus (Jin et al, 2006), and a variety of neurons in the hippocampus (Castillo et al, 1997, Vignes and Collingridge, 1997, Cossart et al, 1998, Frerking et al, 1998, Frerking et al, 1999, Cossart et al, 2002. In accordance with these previous studies, KAR mediated EPSCs in the mEC were defined by their resistance to 100 μM GYKI 52466 or 1 μM NBQX, their small amplitude and slow kinetics, the ability to summate during high frequency stimulation, and their inhibition by 10-50 μM CNQX.…”

“…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.…”

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

“…Kainate receptors are widely expressed in the central nervous system (Wisden and Seeburg, 1993), where they can act pre-and post-synaptically. In the hippocampus, postsynaptic kainate receptors are thought to mediate excitatory transmission via an ionotropic action (Castillo et al, 1997;Cossart et al, 2002;Cossart et al, 1998) and to regulate excitability via a metabotropic function (Melyan et al, 2004;Melyan et al, 2002;Ruiz et al, 2005). Activation of presynaptic kainate receptors regulates glutamate and GABA release (Kullmann, 2001;Rodriguez-Moreno and Lerma, 1998) and modulates excitability in mature (Schmitz et al, 2000) and developing hippocampus.…”