Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons

Petralia, Ronald S.; Wang, Yaxian; Mayat, Ebrahim; Wenthold, Robert J.

doi:10.1002/(sici)1096-9861(19970901)385:3<456::aid-cne9>3.0.co;2-2

Cited by 184 publications

(150 citation statements)

References 62 publications

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“…Whereas a minority of GABAergic interneurons express GluR-B at levels comparable with pyramidal cells (34), in most GABAergic interneurons this subunit is expressed at significantly lower levels. This expression pattern has been documented by in situ hybridization (35)(36)(37) and immunocytochemistry (34,(38)(39)(40)(41). Low GluR-B expression in GABAergic cells affects a number of AMPA receptor properties, including Ca 2ϩ permeability (31,32,42,43), block by polyamines (44), and single-channel conductance (22), and is the molecular basis for certain novel forms of plasticity (44)(45)(46).…”

Section: Discussionmentioning

confidence: 97%

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Fuchs

Doheny

Faulkner

et al. 2001

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

115

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Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in ␥-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance.G amma-frequency (30-to 90-Hz) neuronal oscillations, occurring in a non-time-locked fashion in response to visual stimuli, have been proposed to encode global features of spatially extended stimuli (1). A crucial physiological question concerns how synchrony arises, given the expected slow axonal conduction times in the cortex, estimated to be as low as 0.10-0.15 mm͞ms (2, 3).Network simulations (containing model pyramidal cells, interneurons, and axon conduction delays) predict that tight synchrony between distant sites could arise as an emergent property-without a central pacemaker-when interneurons fire in doublets (4-7). Precise timing of the doublet intervaldetermined in part by ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor mediated excitation from pyramidal cells, especially cells at a distance from the postsynaptic interneuron-provides a signal encoding phase lags between separated neurons; this signal would provide feedback to nearby pyramidal cells, in the form of synaptic inhibition, which would tend to correct for phase differences (ref. 8; Appendix, which is published as supplemental data on the PNAS web site, www.pnas.org).Here we use a combination of simulation, transgenic, and electrophysiological techniques to show that interneuron doublets are necessary for two-site synchrony to occur and that they critically depend on excitatory postsynaptic potential (EPSP) kinetics in interneurons. Experimental ProceduresSimulations. Network simulations of gamma oscillations were performed by using the program described in Traub et al. (5).Briefly, the network consisted of a 96 ϫ 32 cell array of pyramidal neurons, and a superimp...

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Section: Discussionmentioning

confidence: 97%

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Fuchs

Doheny

Faulkner

et al. 2001

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

115

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“…This antibody was a kind gift of Dr. Jean-Marc Fritschy (Institute of Pharmacology, University of Zurich, Zurich, Switzerland). All of these antibodies have been thoroughly characterized and widely used for immunocytochemical localization of glutamate and GABA receptors with light and electron microscopic immunocytochemistry (Petralia and Wenthold, 1992;Petralia et al, 1994Petralia et al, , 1997Fritschy and Mohler, 1995;Nusser and Somogyi, 1997;Takumi et al, 1999b).…”

Section: Methodsmentioning

confidence: 99%

Organization of Ionotropic Glutamate Receptors at Dendrodendritic Synapses in the Rat Olfactory Bulb

Sassoè‐Pognetto

Ottersen

2000

J. Neurosci.

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Dendrodendritic synapses between mitral (or tufted) and granule cells of the olfactory bulb play a major role in the processes of odor discrimination and olfactory learning. Release of glutamate at these synapses activates postsynaptic receptors on the dendritic spines of granule cells, as well as presynaptic NMDA receptors in the mitral cell membrane. However, immunocytochemical studies have failed to demonstrate the presence of ionotropic glutamate receptors in granule cell dendrites. By using a postembedding immunogold procedure, we describe here the precise organization of neurotransmitter receptors at dendrodendritic synapses. We show that there is a selective localization of glutamate and GABA receptors at asymmetric and symmetric synaptic junctions, respectively. In addition, we demonstrate that NMDA and AMPA receptors are clustered at postsynaptic specializations on granule cell spines and that they are extensively colocalized. Conversely, glutamate receptors do not appear to be concentrated in clusters on mitral cell dendrites, suggesting that the presynaptic effects of glutamate are mediated by a small complement of extrasynaptic receptors. By analyzing the subsynaptic distribution of the NR1 and GluR2/3 subunits, we show that they are distributed along the entire extent of the postsynaptic specialization, indicating that both NMDA and AMPA receptors are available for dendrodendritic signaling between mitral and granule cells. These results indicate that the principles recently found to underlie the organization of glutamate receptors at axospinous synapses also apply to dendrodendritic synapses.

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“…Age-related decline of neuronal densities in these regions did not exceed 2-3% (Table 2). Morphological analysis indicated that neurodegeneration occurring in the brain and spinal cord of GluR-B(N) mice follows the GluR-B expression pattern (16) and is preferentially accelerated in the ventral horns of the spinal cord, the basolateral amygdaloid nucleus, and in the ventromedial hypothalamic nucleus. The ventral horns in the spinal cord are essential in the regulation of muscle tone and the execution of movements (17), the basolateral amygdaloid nucleus plays a key role in the perception of fear (18), and the ventromedial hypothalamic nucleus is involved in the regulation of food intake (satiety center) (19).…”

Section: Density Of Neurons In the Brains Of Wt And Glur-b(n) Micementioning

confidence: 99%

Late-onset motoneuron disease caused by a functionally modified AMPA receptor subunit

Kuner

Groom²,

Bresink³

et al. 2005

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

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Amyotrophic lateral sclerosis (ALS) is a devastating disorder of the central nervous system in middle and old age that leads to progressive loss of spinal motoneurons. Transgenic mice overexpressing mutated human Cu 2؉ ͞Zn 2؉ superoxide dismutase 1 (SOD1) reproduce clinical features of the familial form of ALS. However, changes in SOD1 activity do not correlate with severity of motor decline in sporadic cases, indicating that targets unrelated to superoxide metabolism contribute to the pathogenesis of the disease. We show here that transgenic expression in mice of GluR-B(N)-containing L-␣-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) receptors with increased Ca 2؉ permeability leads to late-onset degeneration of neurons in the spinal cord and decline of motor functions. Neuronal death progresses over the entire lifespan but manifests clinically in late adulthood, resembling the course of a slow neurodegenerative disorder. Additional transgenic expression of mutated human SOD1 accelerates disease progression, aggravates the severity of motor decline, and decreases survival. These observations link persistently elevated Ca 2؉ influx through AMPA channels with progressive motor decline and late-onset degeneration of spinal motoneurons, indicating that functionally altered AMPA channels may be causally related to pathogenesis of sporadic ALS in humans.amyotrophic lateral sclerosis ͉ Ca 2ϩ permeable ion channels ͉ GluR-B gene

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Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons

Cited by 184 publications

References 62 publications

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation

Organization of Ionotropic Glutamate Receptors at Dendrodendritic Synapses in the Rat Olfactory Bulb

Late-onset motoneuron disease caused by a functionally modified AMPA receptor subunit

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