GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells

Cossart, Rosa; Esclapez, Monique; Hirsch, J F; Bernard, Christophe; Ben-Ari, Yehezkel

doi:10.1038/2185

Cited by 284 publications

(322 citation statements)

References 38 publications

(55 reference statements)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Laezza

Wilding

Sequeira

et al. 2007

Molecular and Cellular Neuroscience

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Whereas many interacting proteins have been identified for AMPA and NMDA glutamate receptors, fewer are known to directly bind and regulate function of kainate receptors. Using a yeast two-hybrid screen for interacting partners of the C-terminal domain of GluR6a, we identified a novel neuronal protein of the BTB/kelch family, KRIP6. KRIP6 binds to the GluR6a C-terminal domain at a site distinct from the PDZ-binding motif and it co-immunoprecipitates with recombinant and endogenous GluR6. Co-expression of KRIP6 alters GluR6 mediated currents in a heterologous expression system reducing peak current amplitude and steady-state desensitization, without affecting surface levels of GluR6. Endogenous KRIP6 is widely expressed in brain and overexpression of KRIP6 reduces endogenous kainate receptor-mediated responses evoked in hippocampal neurons. Taken together, these results suggest that KRIP6 can directly regulate native kainate receptors and provide the first evidence for a BTB/kelch protein in direct functional regulation of a mammalian glutamate receptor.

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Section: Introductionmentioning

confidence: 99%

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

Laezza

Wilding

Sequeira

et al. 2007

Molecular and Cellular Neuroscience

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“…It has been found previously in this system that KARmediated synaptic responses can be measured in isolation by recording excitatory synaptic responses in the presence of the AMPAR antagonist GYKI 53655 and the NMDAR antagonist APV (Cossart et al, 1998;Frerking et al, 1998). We therefore recorded stimulus-evoked EPSPs in the presence of GYKI 53655 (50 M) and APV (100 M); under these conditions a small and slow KAR-mediated EPSP frequently could be resolved (n ϭ 6) ( Fig.…”

Section: Measurement Of Ampar-and Kar-mediated Epspsmentioning

confidence: 99%

“…Postsynaptic KARs are found in the hippocampus (Castillo et al, 1997;Vignes and Collingridge, 1997;Cossart et al, 1998;Frerking et al, 1998), cortex Isaac, 1999, 2001), cerebellum (Bureau et al, 2000), amygdala (Li and Rogawski, 1998), spinal cord (Li et al, 1999), and retina (DeVries and Schwartz, 1999;DeVries, 2000), and, like AMPARs, KARs are activated by glutamate release under normal conditions. At most of these synapses the EPSC mediated by KARs has a much smaller amplitude than that of AMPARs and much slower kinetics.…”

mentioning

confidence: 99%

AMPA Receptors and Kainate Receptors Encode Different Features of Afferent Activity

Frerking

Ohliger-Frerking

2002

J. Neurosci.

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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.

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“…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.…”

Section: Postsynaptic Kainate Receptors Of the Mecmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

2007

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Although in situ hybridization studies have revealed the presence of kainate receptor (KAR) mRNA in neurons of the rat medial entorhinal cortex (mEC), the functional presence and roles of these receptors are only beginning to be examined. To address this deficiency, whole cell voltage clamp recordings of locally evoked EPSCs were made from mEC layer II and III neurons in combined entorhinal cortex -hippocampal brain slices. Three types of neurons were identified by their electroresponsive membrane properties, locations, and morphologies: stellate-like "Sag" neurons in layer II (S), pyramidal-like "No Sag" neurons in layer III (NS), and "Intermediate Sag" neurons with varied morphologies and locations (IS). Non-NMDA EPSCs in these neurons were composed of two components, and the slow decay component in NS neurons had larger amplitudes and contributed more to the combined EPSC than did those observed in S and IS neurons. This slow component was mediated by KARs and was characterized by its resistance to either GYKI 52466 (100 μM) or NBQX (1 μM), relatively slow decay kinetics, and sensitivity to CNQX (10-50 μM). KAR mediated EPSCs in pyramidal-like NS neurons contributed significantly more to the combined non-NMDA EPSC than did those from S and IS neurons. Layer III neurons of the mEC are selectively susceptible to degeneration in human temporal lobe epilepsy (TLE) and animal models of TLE such as kainate-induced status epilepticus. Characterizing differences in the complement of postsynaptic receptors expressed in injury prone versus injury resistant mEC neurons represents an important step toward understanding the vulnerability of layer III neurons seen in TLE.

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GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells

Cited by 284 publications

References 38 publications

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

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

AMPA Receptors and Kainate Receptors Encode Different Features of Afferent Activity

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

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