GluR1-immunopositive interneurons in rat neocortex

Kharazia, Viktor; Wenthold, Robert J.; Weinberg, Richard J.

doi:10.1002/(sici)1096-9861(19960506)368:3<399::aid-cne6>3.0.co;2-0

Cited by 60 publications

(32 citation statements)

References 60 publications

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“…We observed marked cellular colocalization of GluA1 and parvalbumin in cortical sections prepared from fixed juvenile mice (supplemental Fig S6 A, available at www.jneurosci.org as supplemental material). This observation agrees with previous reports that cortical GABAergic neurons are relatively enriched with the AMPA receptor subunit GluA1 (Kharazia et al, 1996;Narisawa-Saito et al, 1999;Kondo et al, 2000;Kim et al, 2006;Nagano et al, 2007). The resolution of our confocal microscopy system, however, failed to enable us to isolate individual GluA1-positive synapses in parvalbumin-or GAD67-positive cells (data not shown).…”

Section: Enrg1 Elevates Protein Levels and Synaptic Accumulation Of Asupporting

confidence: 92%

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Abe¹,

Namba²,

Kato³

et al. 2011

J. Neurosci.

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Neuregulin-1 (NRG1) signaling is thought to contribute to both neuronal development and schizophrenia neuropathology. Here, we describe the developmental effects of excessive peripheral NRG1 signals on synaptic activity and AMPA receptor expression of GABAergic interneurons in postnatal rodent neocortex. A core peptide common to all NRG1 variants (eNRG1) was subcutaneously administered to mouse pups. Injected eNRG1 penetrated the blood-brain barrier and activated ErbB4 NRG1 receptors in the neocortex, in which ErbB4 mRNA is predominantly expressed by parvalbumin-positive GABAergic interneurons. We prepared neocortical slices from juvenile mice that were receiving eNRG1 subchronically and recorded inhibitory synaptic activity from layer V pyramidal neurons. Postnatal eNRG1 treatment significantly enhanced polysynaptic IPSCs, although monosynaptic IPSCs were not affected. Examination of excitatory inputs to parvalbumin-containing GABAergic interneurons revealed that eNRG1 treatment significantly increased AMPA-triggered inward currents and the amplitudes and frequencies of miniature EPSCs (mEPSCs). Similar effects on mEPSCs were observed in mice treated with a soluble, full-length form of NRG1 type I. Consistent with the electrophysiologic data, expression of the AMPA receptor GluA1 (i.e., GluR1, GluRA) was upregulated in the postsynaptic density/cytoskeletal fraction prepared from eNRG1-treated mouse neocortices. Cortical GABAergic neurons cultured with eNRG1 exhibited a significant increase in surface GluA1 immunoreactivity at putative synaptic sites on their dendrites. These results indicate that NRG1 circulating in the periphery influences postnatal development of synaptic AMPA receptor expression in cortical GABAergic interneurons and may play a role in conditions characterized by GABA-associated neuropathologic processes.

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Section: Enrg1 Elevates Protein Levels and Synaptic Accumulation Of Asupporting

confidence: 92%

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Abe¹,

Namba²,

Kato³

et al. 2011

J. Neurosci.

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“…2 D). Clustered GluR1 immunostaining appeared to be exclusively postsynaptic, because it was seen only in those neurons whose cell body was also GluR1 immunopositive, in agreement with previous work (Petralia and Wenthold, 1992;Craig et al, 1993;Baude et al, 1995;Kharazia et al, 1996). Fluorescent in situ hybridization (data not shown) showed a tight correlation between GluR1 immunostaining and mRNA expression and reconfirmed the localization of GluR1 clusters, seen immunohistochemically, to the dendrites of neurons expressing GluR1 mRNA.…”

Section: The Development Of Glur1 Clusters Correlates With the Onset supporting

confidence: 90%

The Development of Excitatory Synapses in Cultured Spinal Neurons

et al. 1997

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Immunohistochemical studies of synapses in the CNS have demonstrated that glutamate receptors (GluRs) are concentrated at postsynaptic sites in vivo and in vitro (Baude et al., 1995). The mechanisms leading to receptor clustering at excitatory synapses are far less understood than those governing acetylcholine receptor accumulation at the neuromuscular junction (Hall and Sanes,1993) or glycine receptor aggregation at central inhibitory synapses (Kirsch et al., 1993). Using cultured rat spinal cord neurons, we demonstrate that clustering of the AMPA receptor subunit GluR1 is among the earliest events in excitatory synapse formation in vitro, coincident with the onset of miniature EPSCs and in many cases preceding presynaptic vesicle accumulation. Postsynaptic receptor clustering is induced in a highly specific and reiterative pattern, independent of receptor activation, by contact with a subset of axons capable of inducing receptor clusters. The subunit composition of AMPA receptor clusters varied significantly between neurons but was invariant within a given neuron. The presence of either GluR2 or GluR3 was common to all receptor clusters. Neither high-affinity glutamate transporters nor NMDA receptors appeared to be concentrated with AMPA receptor subunits at these excitatory synapses.Key words: GluR1; synaptogenesis; spinal cord; glutamate transporter; glutamate receptors; rat; tissue culture The molecular cloning of the family of glutamate receptors (GluRs), which mediate excitatory synaptic transmission in the CNS, has allowed the development of subunit-specific antibodies that hold promise for elucidating the mechanisms of GluR regulation during central synaptogenesis (Hollmann and Heinemann, 1994). The family of ionotropic GluRs comprise three classes. The first, termed AM PA receptors, includes the homologous subunits GluR1-4, which combine in varying heteromeric complexes to mediate fast, rapidly desensitizing, excitatory transmission. The termination of fast excitatory transmission occurs by either receptor desensitization or glutamate uptake (Trussell and Fischbach, 1989;Holmes, 1995), and high-affinity glutamate transporters from both neurons and glia have recently been cloned (Kanai and Hediger, 1992; Pines et al., 1992). The second class of GluRs, termed NMDA receptors, is formed from two distinct families: N R1, the presence of which is common to all NMDA receptors, and N R2A-D, which complex with NR1 to form f unctional channels (Kutsuwada et al., 1992;Sheng et al., 1994). The high calcium permeability and slow desensitization of the NMDA receptor are thought to mediate both electrical and second messenger signal transduction. A third class of ionotropic GluR, termed the kainate receptor, is composed of the subunits GluR5, 6, and 7, and K A1 and 2. The role of kainate receptors in synaptic transmission is unclear.Work in vivo and in vitro using immunofluorescence and electron microscopy has shown that AM PA and NMDA receptors are concentrated at postsynaptic sites in dendritic spines (Petralia an...

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“…Previous studies using differential centrifu-gation followed by radioligand binding of different subcellular fractions have suggested the localization of 5-HT 2A receptors in cytoplasmic and mitochondrial extracts (Laubeya et al 1986). This cytoplasmic pattern of staining is also observed for various other neurotransmitter receptors, including GluR 1 , AMPA glutamate and mGluR 1 receptors (Molnár et al 1993;Kharazia et al 1996;Petralia et al 1997). …”

Section: Discussionsupporting

confidence: 52%

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor

Yoder

Shih

et al. 1998

J Histochem Cytochem.

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SUMMARY Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and peripheral nervous systems by its interaction with specific neuronal and glial receptors. Fourteen serotonin receptors belonging to seven families have been identified through physiological, pharmacological, and molecular cloning studies. Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are needed to characterize their expression, distribution, and function in embryonic, adult, and pathological tissues. In this article we report the development and characterization of MAbs specific to the serotonin 5-HT 2A receptor. To generate MAbs against 5-HT 2A R, mice were immunized with the N-terminal domain of the receptor. The antigens were produced as glutathionine S-transferase (GST) fusion proteins in insect cells using a Baculovirus expression system. The hybridomas were initially screened by ELISA against the GST-5-HT 2A R recombinant proteins and subsequently against GST control proteins to eliminate clones with unwanted reactivity. They were further tested by Western blotting against recombinant GST-5-HT 2A R, rat and human brain lysate, and lysate from cell lines transfected with 5-HT 2A R cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5-HT 2A R N-terminus, was selected for further characterization. G186-1117 reacted with a band of molecular size 55 kD corresponding to the predicted size of 5-HT 2A R in lysates from rat brain and a 5-HT 2A R-transfected cell line. Its specificity was further confirmed by adsorption of immunoreactivity with recombinant 5-HT 2A R but not with recombinant 5-HT 2B R and 5-HT 2C R. Rat brain sections and Schwann cell cultures were immunohistochemically labeled with this MAb. G186-1117 showed differential staining in various regions of the rat brain, varying from regions with no staining to regions of intense reactivity. In particular, staining of cell bodies and dendrites of the pyramidal neurons in the cortex was observed, which is in agreement with observations of electrophysiological studies. (J Histochem Cytochem 46:811-824, 1998)

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GluR1-immunopositive interneurons in rat neocortex

Cited by 60 publications

References 60 publications

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

The Development of Excitatory Synapses in Cultured Spinal Neurons

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor

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GluR1-immunopositive interneurons in rat neocortex

Cited by 60 publications

References 60 publications

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

The Development of Excitatory Synapses in Cultured Spinal Neurons

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT2AReceptor

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Product

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Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor