Kainate Receptor-Mediated Responses in the CA1 Field of Wild-Type and GluR6-Deficient Mice

Bureau, Ingrid; Bischoff, Serge; Heinemann, Sabine; Mulle, Christophe

doi:10.1523/jneurosci.19-02-00653.1999

Cited by 201 publications

(230 citation statements)

References 33 publications

(52 reference statements)

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“…GluR5-containing kainate receptors are expressed primarily in interneurons (35). We examined the effect of the selective GluR5-containing kainate receptor agonist ATPA (36) and antagonist LY293558 (25) on sIPSCs in interneurons.…”

Section: Resultsmentioning

confidence: 99%

Astrocyte-mediated activation of neuronal kainate receptors

Liu

Xu²,

Arcuino³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

194

126

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Exogenous kainate receptor agonists have been shown to modulate inhibitory synaptic transmission in the hippocampus, but the pathways involved in physiological activation of the receptors remain largely unknown. Accumulating evidence indicates that astrocytes can release glutamate in a Ca 2؉ -dependent manner and signal to neighboring neurons. We tested the hypothesis that astrocyte-derived glutamate activates kainate receptors on hippocampal interneurons. We report here that elevation of intracellular Ca 2؉ in astrocytes, induced by uncaging Ca 2؉ , o-nitrophenyl-EGTA, increased action potential-driven spontaneous inhibitory postsynaptic currents in nearby interneurons in rat hippocampal slices. This effect was blocked by ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)͞kainate glutamate receptor antagonists, but not by selective AMPA receptor or N-methyl-Daspartate receptor antagonists. This pharmacological profile indicates that kainate receptors were activated during Ca 2؉ elevation in astrocytes. Kainate receptors containing the GluR5 subunit seemed to mediate the observed effect because a selective GluR5-containing kainate receptor antagonist blocked the changes in sIPSCs induced by Ca 2؉ uncaging, and bath application of a selective GluR5-containing receptor agonist robustly potentiated sIPSCs. When tetrodotoxin was included to block action potentials, Ca 2؉ uncaging induced a small decrease in the frequency of miniature inhibitory postsynaptic currents, which was not affected by AMPA͞kainate receptor antagonists. Our data suggest that an astrocyte-derived, nonsynaptic source of glutamate represents a signaling pathway that can activate neuronal kainate receptors. By modulating the activity of interneurons, astrocytes may play a critical role in circuit function of hippocampus.A strocytes have traditionally been considered to function as supporting cells in the central nervous system. During the past decade, it has become increasingly clear that they actively participate in intercellular communication in the brain (1-3). They are endowed with a variety of ion channels and receptors (4-6), and they display a form of excitability by changing the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) (1-3, 7-9). Both application of neurotransmitters (1, 5, 10, 11) and electrical stimulation of neuronal pathways (12, 13) increase [Ca 2ϩ ] i in astrocytes. Thus, astrocytes sense and respond to neuronal activity by increasing [Ca 2ϩ ] i . The functional significance of this calcium signaling is still not well understood, but growing evidence suggests that it may trigger the release of glutamate and other neuroactive substances from astrocytes and thereby play a pivotal role in providing feedback to adjacent neurons and blood vessels. Such feedback can result in changes in neuronal excitability (8, 14-17), modulation of synaptic strength (18)(19)(20), an increase in neuronal [Ca 2ϩ ] i (8, 11), and a decrease in vascular tone (21).The study of astrocyte-neuron interactions is hampered by the lack of spec...

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Section: Resultsmentioning

confidence: 99%

Astrocyte-mediated activation of neuronal kainate receptors

Liu

Xu²,

Arcuino³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

194

126

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“…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.…”

Section: Postsynaptic Kars In Neurons Of the Superficial Mecmentioning

confidence: 99%

“…Furthermore, the expression of postsynaptic KARs has been shown to be restricted in a cellular and subcellular manner. For instance, CA3 pyramidal neurons of the hippocampus have been shown to have postsynaptic KARs that mediate a substantial portion of the synaptic response, specifically at their mossy fiber synapse, while CA1 neurons do not have postsynaptic KAR mediated EPSCs (Castillo et al, 1997, Frerking et al, 1998, Bureau et al, 1999, Lerma et al, 2001. Additionally, KARs in hippocampal CA3 neurons have been shown to underlie the kainate-induced gamma oscillations observed in these neurons (Fisahn et al, 2004).…”

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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“…1 and 2). Although KA-Rs are also present in CA1 pyramidal neurons, these receptors are not activated synaptically (3,4). In the CA1 region, however, KA-Rs inhibit glutamate release presynaptically (5-7) and also regulate action potential (AP)-dependent GABA release from interneurons; studies have shown that the frequency of AP-independent GABA release is either unaffected (8)(9)(10) or inhibited by KA-R activation (11).…”

mentioning

confidence: 99%

Alcohol potently inhibits the kainate receptor-dependent excitatory drive of hippocampal interneurons

Carta

Ariwodola²,

Weiner³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Kainate receptors (KA-Rs) are members of the glutamate-gated family of ionotropic receptors, which also includes N-methyl-Daspartate (NMDA) and ␣-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. KA-Rs are important modulators of interneuron excitability in the CA1 region of the hippocampus. Activation of these receptors enhances interneuron firing, which robustly increases spontaneous inhibitory postsynaptic currents in pyramidal neurons. We report here that ethanol (EtOH) potently inhibits this KA-R-mediated effect at concentrations as low as those that can be achieved in blood after the ingestion of just 1-2 drinks (5-10 mM). Pressure application of kainate, in the presence of AMPA and NMDA receptor antagonists, evoked depolarizing responses in interneurons that triggered repetitive action potential firing. EtOH potently inhibited these responses to a degree that was sufficient to abolish action potential firing. This effect appears to be specific for KA-Rs, as EtOH did not affect action potential firing triggered by AMPA receptor-mediated depolarizing responses. Importantly, EtOH inhibited interneuron action potential firing in response to KA-R activation by synaptically released glutamate, suggesting that our findings are physiologically relevant. KA-R-dependent modulation of glutamate release onto pyramidal neurons was not affected by EtOH. Thus, EtOH increases excitability of pyramidal neurons indirectly by inhibiting the KA-R-dependent drive of ␥-aminobutyric acid (GABA)ergic interneurons. We postulate that this effect may explain, in part, some of the paradoxical excitatory actions of this widely abused substance. The excitatory actions of EtOH may be perceived as positive by some individuals, which could contribute to the development of alcoholism.K ainate receptors (KA-Rs) are glutamate-gated ion channels that play important roles in the regulation of hippocampal excitability. In mossy fiber-to-CA3 pyramidal neuron synapses, KA-Rs mediate synaptic currents and plasticity and modulate glutamate release presynaptically (reviewed in refs. 1 and 2). Although KA-Rs are also present in CA1 pyramidal neurons, these receptors are not activated synaptically (3, 4). In the CA1 region, however, KA-Rs inhibit glutamate release presynaptically (5-7) and also regulate action potential (AP)-dependent GABA release from interneurons; studies have shown that the frequency of AP-independent GABA release is either unaffected (8-10) or inhibited by KA-R activation (11). Activation of KA-Rs by micromolar concentrations of KA inhibits evoked ␥-aminobutyric acid type A (GABA A ) receptor (GABA A -R)-mediated inhibitory postsynaptic currents (eIPSCs) in CA1 pyramidal neurons (8,9,(12)(13)(14)(15). However, the precise mechanism and the physiological importance of this effect are a matter of controversy (reviewed in refs. 1 and 16). This effect was initially interpreted to indicate that activation of interneuronal KA-Rs exerts a disinhibitory effect on CA1 pyramidal neurons, but subsequent studies have challenge...

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Kainate Receptor-Mediated Responses in the CA1 Field of Wild-Type and GluR6-Deficient Mice

Cited by 201 publications

References 33 publications

Astrocyte-mediated activation of neuronal kainate receptors

Astrocyte-mediated activation of neuronal kainate receptors

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

Alcohol potently inhibits the kainate receptor-dependent excitatory drive of hippocampal interneurons

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