Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons

Rodríguez‐Moreno, Antonio; López-Garcı́a, Juan Carlos; Lerma, Juan

doi:10.1073/pnas.97.3.1293

Cited by 149 publications

(125 citation statements)

References 28 publications

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“…The increase in sIPSCs in interneurons in response to astrocytic calcium elevation was blocked by the AMPA͞kainate receptor antagonists, CNQX and NBQX, and by LY293558, a selective GluR5-containing kainate receptor antagonist (25), but not by a SYM 2206, a selective AMPA receptor antagonist (33,34). These findings suggest that the effect is mediated by activation of GluR5-containing kainate receptors.…”

Section: Discussionmentioning

confidence: 50%

“…In the presence of the selective ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist SYM 2206 (50 M) (33,34) together with the N-methyl-Daspartate (NMDA) receptor antagonist CPP (5 M), Ca 2ϩ uncaging in astrocytes (peak ⌬F͞F 0 ϭ 189 Ϯ 23%, n ϭ 9) produced a similar increase in the frequency of sIPSCs in interneurons (Fig. 3), which was not significantly different from that observed in control slices, in the absence of the blockers (P Ͼ 0.3, ANOVA).…”

Section: Resultsmentioning

confidence: 99%

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Astrocyte-mediated activation of neuronal kainate receptors

Liu

Xu²,

Arcuino³

et al. 2004

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

195

128

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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: Discussionmentioning

confidence: 50%

Section: Resultsmentioning

confidence: 99%

Astrocyte-mediated activation of neuronal kainate receptors

Liu

Xu²,

Arcuino³

et al. 2004

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

195

128

View full text Add to dashboard Cite

show abstract

“…Kainate receptors expressed in dorsal root ganglion cells are coupled with G proteins and inhibit Ca 2ϩ channels upon activation with agonists (38). In the hippocampus, both at the inhibitory (39,40) and excitatory (41) synapses, presynaptic kainate receptors are proposed to couple with G proteins for inhibiting transmitter release. Although we did not observe kainate receptor-dependent presynaptic inhibition at the calyx of Held terminal, a common intracellular mechanism might underlie the presynaptic inhibition by kainate receptors and AMPA receptors.…”

Section: Discussionmentioning

confidence: 99%

G protein-dependent presynaptic inhibition mediated by AMPA receptors at the calyx of Held

Takago

Nakamura

Takahashi

2005

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

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The ␣-amino-3-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an ionotropic receptor mediating excitatory synaptic transmission, but it can also interact with intracellular messengers. Here we report that, at the calyx of Held in the rat auditory brainstem, activation of AMPARs induced inward currents in the nerve terminal and inhibited presynaptic Ca 2؉ currents (IpCa), thereby attenuating glutamatergic synaptic transmission. The AM-PAR-mediated I pCa inhibition was disinhibited by a strong depolarizing pulse and occluded by the nonhydrolyzable GTP analog GTP␥S loaded into the terminal. We conclude that functional AMPARs are expressed at the calyx of Held nerve terminal and that their activation inhibits voltage-gated Ca 2؉ channels by an interaction with heterotrimeric GTP-binding proteins (G proteins). Thus, at a central glutamatergic synapse, presynaptic AMPARs have a metabotropic nature and regulate transmitter release by means of G proteins.calcium channel ͉ excitatory postsynaptic current ͉ synapse ͉ glutamate

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“…The administration of kainate to rodents leads to epileptiform seizures and patterns of neuronal damage similar to those observed in humans (5). Kainate administration is thought to suppress GABAergic neurotransmission in the hippocampus, which results in hyperexcitability states of CA1 and CA3 pyramidal neurons, ultimately leading to the deaths of these neuronal populations by excitotoxic mechanisms (6,22,57). Glutamate excitotoxicity and hippocampal neuronal degeneration were previously observed after infection of mouse brains with the HNT strain of measles virus (2) and were more recently observed with neuroadapted Sindbis virus (45).…”

Section: Vol 79 2005 Ifn-␥ Mediates Borna Disease Virus Clearance Fmentioning

confidence: 99%

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

Hausmann¹,

Pagenstecher

Baur³

et al. 2005

J Virol

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Borna disease virus (BDV) frequently causes meningoencephalitis and fatal neurological disease in young but not old mice of strain MRL. Disease does not result from the virus-induced destruction of infected neurons. Rather, it is mediated by H-2 k -restricted antiviral CD8 T cells that recognize a peptide derived from the BDV nucleoprotein N. Persistent BDV infection in mice is not spontaneously cleared. We report here that N-specific vaccination can protect wild-type MRL mice but not mutant MRL mice lacking gamma interferon (IFN-␥) from persistent infection with BDV. Furthermore, we observed a significant degree of resistance of old MRL mice to persistent BDV infection that depended on the presence of CD8 T cells. We found that virus initially infected hippocampal neurons around 2 weeks after intracerebral infection but was eventually cleared in most wild-type MRL mice. Unexpectedly, young as well as old IFN-␥-deficient MRL mice were completely susceptible to infection with BDV. Moreover, neurons in the CA1 region of the hippocampus were severely damaged in most diseased IFN-␥-deficient mice but not in wild-type mice. Furthermore, large numbers of eosinophils were present in the inflamed brains of IFN-␥-deficient mice but not in those of wild-type mice, presumably because of increased intracerebral synthesis of interleukin-13 and the chemokines CCL1 and CCL11, which can attract eosinophils. These results demonstrate that IFN-␥ plays a central role in host resistance against infection of the central nervous system with BDV and in clearance of BDV from neurons. They further indicate that IFN-␥ may function as a neuroprotective factor that can limit the loss of neurons in the course of antiviral immune responses in the brain.

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Two populations of kainate receptors with separate signaling mechanisms in hippocampal interneurons

Cited by 149 publications

References 28 publications

Astrocyte-mediated activation of neuronal kainate receptors

Astrocyte-mediated activation of neuronal kainate receptors

G protein-dependent presynaptic inhibition mediated by AMPA receptors at the calyx of Held

CD8 T Cells Require Gamma Interferon To Clear Borna Disease Virus from the Brain and Prevent Immune System-Mediated Neuronal Damage

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