Publications
220 results found
Bahn S, Harvey RJ, Darlison MG, et al., 1996, Conservation of gamma-aminobutyric acid type A receptor alpha 6 subunit gene expression in cerebellar granule cells, J Neurochem, Vol: 66, Pages: 1810-1818, ISSN: 0022-3042
Wisden W, Korpi ER, Bahn S, 1996, The cerebellum: a model system for studying GABA-A receptor diversity, Neuropharmacology, Vol: 35, Pages: 1139-1160, ISSN: 0028-3908
The basic unsolved questions concerning GABAA receptors are: "How many receptor subtypes exist?", "What subtypes are used by which types of neuron and where are they located on the cell?", and "What are the functions of the different subtypes?" As described in this Review, the cerebellum is an ideal vertebrate brain region for investigating these issues.
Makela R, Lehtonen M, Wisden W, et al., 1996, Blunted furosemide action on cerebellar GABA-A receptors in ANT rats selectively bred for high alcohol sensitivity, Neuropharmacology, Vol: 35, Pages: 1493-1502, ISSN: 0028-3908
Furosemide specifically reverses the inhibition by gamma-aminobutyric acid (GABA) of t-[35S]-butylbicyclophosphorothionate ([35S]TBPS) binding and increases the basal [35S]TBPS binding to the cerebellar granule cell layer GABAA receptors. For the selectivity of furosemide, an interplay between GABAA receptor alpha 6 and beta 2 or beta 3 subunits is needed. We have now investigated the furosemide sensitivity of cerebellar [35S]TBPS binding in the alcohol-sensitive (ANT) rat line that harbors a pharmacologically critical point mutation in the alpha 6 subunit [alpha 6 (Q1000)], increasing benzodiazepine affinity of the normally insensitive alpha 6-containing receptors. ANT receptors were less efficiently affected by furosemide, while a normal GABAA receptor antagonism was observed with a specific GABAA receptor antagonist SR 95531. Reduced [3H]muscimol binding in ANT samples and small alterations in situ hybridization signals for alpha 1, alpha 6, beta 2, beta 3, gamma 2 and delta subunit mRNAs failed to correlate with impaired cerebellar furosemide efficacy in individual animals. The alpha 6 (q100) ANT mutation was not responsible for the reduced efficacy of furosemide in the ANT rat line, as judged from the potent furosemide antagonism in recombinant ANT-type alpha 6 (Q100)beta 3 gamma 2 receptors. This data suggest that presence of a novel abnormality in the structure and/or expression of alpha 6 subunit-containing GABAA receptors in the ANT rat line.
Jones A, Bahn S, Grant AL, et al., 1996, Characterization of a cerebellar granule cell-specific gene encoding the gamma-aminobutyric acid type A receptor alpha 6 subunit, J Neurochem, Vol: 67, Pages: 907-916, ISSN: 0022-3042
The alpha 6 subunit of gamma-aminobutyric type A receptors is a marker for cerebellar granule cells and is an attractive candidate to study cell-specific gene expression in the brain. The mouse alpha 6 subunit gene has nine exons and spans approximately 14 kb. The largest intron (intron 8) is approximately 7 kb. For a minority of mRNAs, a missplice of the first exon was identified that disrupts the signal peptide and most likely results in the production of nonfunctional protein. The gene is transcribed from a TATA-less promoter that uses multiple start sites. Using transgenic mice, it was found that the proximal 0.5 kb of the rat alpha 6 gene upstream region confers expression on a beta-galactosidase reporter gene. One founder gave rise to a line with cerebellar granule cell-specific expression, although expression varied with lobule region. Other founders had ectopic but neuron-specific expression, with beta-galactosidase found in cerebellar Purkinje cells, neocortex, thalamus, hippocampus, caudate-putamen, and inferior colliculi. Thus, we have defined a region containing the basal promoter of the alpha 6 subunit gene and that confers neuron-specific expression.
Grant AL, Jones A, Thomas KL, et al., 1996, Characterization of the rat hippocalcin gene: the 5' flanking region directs expression to the hippocampus, Neuroscience, Vol: 75, Pages: 1099-1115, ISSN: 0306-4522
WISDEN W, 1995, THE MOLECULAR-BIOLOGY OF EXCITATORY AND INHIBITORY AMINO-ACID RECEPTORS WITH A SPECIAL FOCUS ON THE HYPOTHALAMUS, Publisher: CAMBRIDGE UNIV PRESS, Pages: S7-S9, ISSN: 0022-3751
KEMPF HG, BRANDLE TU, WISDEN W, et al., 1995, GAMMA-AMINOBUTYRIC ACID(A) RECEPTOR, MESSENGERRNA DETECTION IN COCHLEAR SURFACE PREPARATIONS - AN IN-SITU HYBRIDIZATION INVESTIGATION, HNO, Vol: 43, Pages: 12-18, ISSN: 0017-6192
- Author Web Link
- Cite
- Citations: 3
Kempf HG, Brändle TU, Wisden W, et al., 1995, [Detection of GABA(A) receptor mRNA in cochlear tissue. An in situ hybridization study]., HNO, Vol: 43, Pages: 12-18, ISSN: 0017-6192
Gamma-aminobutyric acid (GABA) and the GABAergic system play an important role in the efferent modulation of cochlear function. We examined surface preparations of guinea pig and mouse cochleae by in situ hybridization using radioactive labelled oligonucleotides for several subunits of the GABAA receptor. Frozen sections of rat and guinea pig brain (cortex, hippocampus, cerebellum) served as controls. In the mouse cochlea the mRNA of the alpha-1 and alpha-5, beta-1 and gamma-1 subunit were detected, while in guinea pig cochlea mRNA of the alpha-1, alpha-4, alpha-5, and gamma-1 subunit of the GABAA receptor were found. Positive signals were located in the regions of the outer hair cells and had a weaker intensity in the inner hair cells. In the brain sections the several subunits were detected in a variable distribution in the cerebellum, hippocampus and cortical regions. Rat specimens exhibited stronger signals than guinea pig brain sections. These investigations have extended previous results of immunocytochemical experiments from our laboratory demonstrating mRNA sequences of GABAA receptor subunits in the mammalian inner ear. Detection of these nucleotide sequences using surface preparations of the cochlea on a molecular level by in situ hybridization supports the importance of GABA as a cochlear neurotransmitter. Furthermore, it can be concluded that the mammalian cochlea is able to express a GABA-dependent neurotransmission system.
Wisden W, 1995, Structure and distribution of multiple GABA-A receptor subunits with special reference to the cerebellum, Ann N Y Acad Sci, Vol: 757, Pages: 506-515, ISSN: 0077-8923
Tolle TR, Berthele A, Zieglgansberger W, et al., 1995, Flip and Flop variants of AMPA receptors in the rat lumbar spinal cord, Eur J Neurosci, Vol: 7, Pages: 1414-1419, ISSN: 0953-816X
The expression of eight messenger RNA splice forms encoding the Flip and Flop variants of AMPA receptor subunits GluR-A to -D in the rat lumbar spinal cord was examined by in situ hybridization using specific oligonucleotides. In the dorsal horn (laminae I, II and III) the predominant mRNA was GluR-B Flip. Much lower levels of GluR-A Flip were found in lamina I and in superficial parts of lamina II outer. In the ventral horn, motor neurons expressed mainly GluR-B Flip, GluR-C Flip and Flop, and GluR-D Flip. Serial sectioning through large motor neurons indicated that a given cell contained, for example, both GluR-C Flip and Flop splice types.
Hunt SP, McNaughton LA, Jenkins R, et al., 1995, Immediate-early gene activation as a window on mechanism in the nervous system., Immediate-Early Genes in the Central Nervous System, Editors: Tolle, Schadrack, Ziegelgaensberger, Berlin, Publisher: Springer-Verlag, Pages: 18-34
KEMPF HG, BRANDLE TU, WISDEN W, et al., 1994, GAMMA-AMINOBUTYRIC ACID(A)-RECEPTOR MESSENGER-RIBONUCLEIC-ACID (ALPHA-1 SUBUNIT) DETECTION BY IN-SITU HYBRIDIZATION, EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY, Vol: 251, Pages: 61-64, ISSN: 0937-4477
- Author Web Link
- Cite
- Citations: 5
Wisden W, Morris BJ, 1994, In situ hybridization protocols for the brain, Publisher: Academic Pr
In situ hybridization is an important technique in probing the cellular sites of gene expression within a tissue.
Wisden W, Morris BJ, 1994, In situ hybridization with synthetic oligonucleotide probes., In situ hybridization protocols for the brain, Editors: Wisden, Morris, Publisher: Academic Pr, Pages: 9-34
In situ hybridization is an important technique in probing the cellular sites of gene expression within a tissue.
Bahn S, Volk B, Wisden W, 1994, Kainate receptor gene expression in the developing rat brain, J Neurosci, Vol: 14, Pages: 5525-5547, ISSN: 0270-6474
Schoepfer R, Monyer H, Sommer B, et al., 1994, Molecular biology of glutamate receptors, Progress in Neurobiology, Pages: 353-357
The ligand-gated receptors for L-glutamate play a central role in acute neuronal degeneration. Recently cDNAs have been isolated for subunits of several glutamate receptor subtypes. By sequence homology all these subunits clearly belong to one large gene family. Several subfamilies exist and match roughly previously pharmacologically and electrophysiologically defined subtypes of glutamate receptors. Currently four genes (GluR A, B, C and D) are known that code for the AMPA subtypes of glutamate receptors. Recombinant expression of wild type and mutated sequences identified a critical residue in the putative TM2 channel-lining segment that controls Ca2+ ion permeability. The arginine (R) found in GluR B subunits at that position renders AMPA channels impermeable for Ca2+ ions, whereas glutamine (Q) containing GluR A, C and D subunits give rise to Ca2+ permeable channels. RNA editing converts the genomically encoded glutamine codon into the arginine codon found in GluR B cDNAs for the Q/R site. NMDA subtypes of glutamate receptors are formed after coexpression of the NR1 cDNA with a cDNA of the NR2 family. Depending on the member of the NR2 family used, NMDA receptors with different kinetical and pharmacological properties are generated. Common to all channels of these NMDA receptors is a high permeability for Ca2+ ions and a voltage dependent block by Mg2+ ions. All currently known NMDA receptor subunits have an asparagine at the Q/R homologous position. We found that this residue is critical for Mg2+ block and Ca2+ permeability of NMDA receptor channels.
Wisden W, Morris BJ, 1994, Studying gene expression in neural tissues using in situ hybridization. The Introduction to In Situ Hybridization Protocols for the Brain - The Biological Techniques Series., In situ hybridization protocols for the brain, Editors: Wisden, Morris, Publisher: Academic Pr, Pages: 1-5
In situ hybridization is an important technique in probing the cellular sites of gene expression within a tissue.
Lomeli H, Sprengel R, Laurie DJ, et al., 1993, The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family, FEBS Lett, Vol: 315, Pages: 318-322, ISSN: 0014-5793
We have characterized a second member (delta-2) of a new class of subunits for the ligand-gated excitatory amino acid receptor superfamily. The sequence of delta-2 exhibits an average identity of 25% and 18.5% to the non-NMDA and NMDA receptor subunits, respectively. The rat delta-2 gene is expressed predominantly in Purkinje cells of the cerebellum whereas only low levels of delta-1 transcripts are found in the adult brain. However, delta-1 gene expression undergoes a pronounced developmental peak, with particularly high mRNA levels in the caudate putamen of late embryonic/early postnatal stages.
Wisden W, Seeburg PH, 1993, Mammalian ionotropic glutamate receptors, Curr Opin Neurobiol, Vol: 3, Pages: 291-298, ISSN: 0959-4388
Exciting new milestones in glutamate receptor (GluR) channel research include the following: the cloning of N-methyl-D-aspartate (NMDA) receptors; delineation of molecular determinants for ion flow through glutamate-gated channels; the discovery that Ca2+ permeability of non-NMDA receptor channels is determined by RNA editing; the construction of antibodies and their use in immunocytochemical localizations of alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA) receptor subunits in the rat brain; and the return to prominence of the high-affinity kainate site with the publication of cDNA sequences for subunits (GluR-5, -6, -7; KA-1, -2) constituting subtypes of this site. Major unresolved issues comprise the transmembrane topology and subunit stoichiometries of native receptor channels.
Wisden W, Parker EM, Mahle CD, et al., 1993, Cloning and characterization of the rat 5-HT5B receptor. Evidence that the 5-HT5B receptor couples to a G protein in mammalian cell membranes, FEBS Lett, Vol: 333, Pages: 25-31, ISSN: 0014-5793
A gene encoding a novel G protein-coupled 5-hydroxytryptamine (5-HT) receptor, termed 5-HT5B, was cloned. The ligand binding profile of this receptor is distinct from that of other cloned 5-HT receptors. The 5-HT5B receptor couples to a G protein in COS1 cell membranes; however, activation of the 5-HT5B receptor does not appear to alter either cAMP accumulation or phosphoinositide turnover in a variety of fibroblast cell lines. In the rat brain, 5-HT5B gene expression occurs predominantly in the medial habenulae and hippocampal CA1 cells of the adult. Little expression is seen during embryonic development.
Tolle TR, Berthele A, Zieglgansberger W, et al., 1993, The differential expression of 16 NMDA and non-NMDA receptor subunits in the rat spinal cord and in periaqueductal gray, J Neurosci, Vol: 13, Pages: 5009-5028, ISSN: 0270-6474
Diverse arrays of glutamate-gated channels in the spinal cord and associated pathways are partly responsible for sensory input, for altered sensitivity to peripheral stimuli during inflammation, and for generation of motor patterns. The expression of 16 genes, encoding all known subunits for the NMDA receptor (NR1, NR2A to NR2D), AMPA/low-affinity kainate (GluR-A to -D), high-affinity kainate ionotropic receptors (KA-1, -2, GluR-5 to -7) and two orphan receptor subunits (delta-1 and -2) was examined by in situ hybridization in rat lumbar spinal cord, and in the periaqueductal gray. Subunit mRNAs for GluR-A, -B Flip, KA-2, and NR1 were abundant in the dorsal horn, with NR2D lightly expressed. Occasional cells in lamina II contained NR2C mRNA. While the GluR-A gene was preferentially expressed in laminae I and II-outer, GluR-B mRNA was evenly expressed throughout all superficial laminae (I, II-outer, II-inner, and III). Large neurons in laminae IV and V expressed mainly NR1, GluR-C, and to lesser extents the GluR-B, GluR-D, and NR2D genes. Lamina I contained occasional cells expressing the GluR-5 gene, whereas GluR-7 mRNA was present in scattered cells in all superficial laminae. In motor neurons, GluR-B Flip, -C Flip, -D Flip, and NR1 mRNAs were expressed heavily, and those of NR2D and KA-1 weakly. Possibly connected to the RNA editing mechanism, GluR-B was the only subunit whose RNA was concentrated in motor neuron cell nuclei in addition to the cytoplasm. delta-1 and -2 mRNAs were found at low levels throughout the gray matter. NR2A, NR2B, and GluR-6 mRNAs were undetectable. For the periaqueductal gray, prominent mRNAs were GluR-A, -B, and NR1. An en passant observation concerned high levels of NR2C mRNA in the pineal gland.
Wisden W, Seeburg PH, 1993, A complex mosaic of high-affinity kainate receptors in rat brain, J Neurosci, Vol: 13, Pages: 3582-3598, ISSN: 0270-6474
The significance for CNS function of glutamate-gated cation channels that exhibit high-affinity kainate sites is not understood. Such receptors, which on dorsal root ganglia and in recombinant systems exhibit currents that rapidly desensitize to kainate application, have not been detected electrophysiologically in the brain. However, a comparison of the distribution of mRNAs encoding five glutamate receptor subunits exhibiting high-affinity kainate sites (GluR-5-GluR-7, KA-1, and KA-2) indicates that high-affinity kainate receptors are most likely involved in all central neuronal circuits of the rat brain. The KA-1 mRNA occurs mainly in the CA3 field of the hippocampus and dentate gyrus, with much lower amounts being found in inner cortical layers, cerebellar Purkinje cells, and white matter (e.g., corpus callosum and anterior commissure). The KA-2 gene is widely expressed in many neuronal nuclei including layers II-VI of neocortex, hippocampal pyramidal (CA1-CA3) and dentate granule cells, septal nuclei such as the bed nucleus of the stria terminalis, medial preoptic, suprachiasmatic, and ventral medial hypothalamic nuclei, dorsal raphe, locus coeruleus, and cerebellar granule cells. KA-2 mRNA is also found in the pineal gland. GluR-5 transcripts are in the cingulate and piriform cortex, the subiculum, lateral septal nuclei, anteroventral thalamus, suprachiasmatic nucleus, the tegmental nuclei, pontine nuclei, and Purkinje cells. GluR-6 mRNA is most abundant in cerebellar granule cells, with lower levels in caudate-putamen and the pyramidal cell layers and dentate granule cells of hippocampus. The GluR-7 gene is prominently expressed in the inner neocortical layers and some cells in layer II, subiculum, caudate-putamen, reticular thalamus, ventral medial hypothalamic nucleus, pontine nuclei, and in putative stellate/basket cells in the cerebellum. These findings suggest that a complex mosaic of receptor variants underlies the high-affinity kainate receptor in the v
LAURIE DJ, WISDEN W, SEEBURG PH, 1992, THE DISTRIBUTION OF 13 GABA-A RECEPTOR SUBUNIT MESSENGER-RNAS IN THE RAT-BRAIN .3. EMBRYONIC AND POSTNATAL-DEVELOPMENT, JOURNAL OF NEUROSCIENCE, Vol: 12, Pages: 4151-4172, ISSN: 0270-6474
- Author Web Link
- Cite
- Citations: 1011
SOMMER B, MONYER H, WISDEN W, et al., 1992, GLUTAMATE-GATED ION CHANNELS IN THE BRAIN - GENETIC MECHANISM FOR GENERATING MOLECULAR AND FUNCTIONAL DIVERSITY, Publisher: GEORG THIEME VERLAG KG, Pages: 209-210, ISSN: 0004-4172
- Author Web Link
- Cite
- Citations: 10
Wisden W, Seeburg PH, 1992, GABA-A receptor channels: from subunits to functional entities, Curr Opin Neurobiol, Vol: 2, Pages: 263-269, ISSN: 0959-4388
GABAA receptor channels mediate postsynaptic inhibition. The functional diversity of these receptors rests on differences in subunit composition and on a large repertoire of subunits. Subunit expression patterns in the brain have been found to predict in vivo compositions of GABAA receptors. In addition, molecular determinants underlying the differential binding properties of allosteric ligands to receptor subtypes have been identified.
Monyer H, Sommer B, Wisden W, et al., 1992, Glutamate-gated ion channels in the brain: genetic mechanisms for generating molecular and functional diversity., Excitatory Amino Acids. Fidia Research Foundation Symposium, Publisher: Thieme Verlag, Pages: 29-33
LAURIE DJ, WISDEN W, SEEBURG PH, 1992, THE DISTRIBUTION OF 13 GABA(A) RECEPTOR SUBUNIT MESSENGER-RNAS IN THE DEVELOPING RAT-BRAIN, Publisher: OXFORD UNIV PRESS UNITED KINGDOM, Pages: 6-6, ISSN: 0953-816X
GREFERATH U, MULLER F, WASSLE H, et al., 1992, LOCALIZATION OF GABA(A)-RECEPTORS IN THE RAT RETINA, Publisher: OXFORD UNIV PRESS UNITED KINGDOM, Pages: 129-129, ISSN: 0953-816X
Herb A, Wisden W, Luddens H, et al., 1992, The third gamma subunit of the gamma-aminobutyric acid type A receptor family, Proc Natl Acad Sci U S A, Vol: 89, Pages: 1433-1437, ISSN: 0027-8424
Cloned cDNAs encoding a member of the gamma-aminobutyric acid type A receptor gamma-subunit class were isolated from rat-brain-mRNA-derived libraries. The gamma 3 mRNA is present in cortex, claustrum, caudate putamen, and some thalamic nuclei, particularly the medial geniculate nucleus, where it is the predominant gamma-subunit transcript. The gamma 3 gene is expressed at very low levels in cerebellum and hippocampus. In coexpression experiments with the alpha 1 and beta 2 subunits, gamma 3 imparts benzodiazepine binding to gamma-aminobutyric acid type A receptors and forms gamma-aminobutyric acid-gated benzodiazepine-modulated chloride channels that exhibit a larger conductance than alpha 1 beta 2 receptor channels. Furthermore, the presence of gamma 3 in place of gamma 2 in alpha 1 beta 2 gamma x receptors generates a marked decrease in the affinity of agonists while leaving the affinity of antagonists or negative modulators largely unaffected.
Wisden W, Laurie DJ, Monyer H, et al., 1992, The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon, J Neurosci, Vol: 12, Pages: 1040-1062, ISSN: 0270-6474
The expression patterns of 13 GABAA receptor subunit encoding genes (alpha 1-alpha 6, beta 1-beta 3, gamma 1-gamma 3, delta) were determined in adult rat brain by in situ hybridization. Each mRNA displayed a unique distribution, ranging from ubiquitous (alpha 1 mRNA) to narrowly confined (alpha 6 mRNA was present only in cerebellar granule cells). Some neuronal populations coexpressed large numbers of subunit mRNAs, whereas in others only a few GABAA receptor-specific mRNAs were found. Neocortex, hippocampus, and caudate-putamen displayed complex expression patterns, and these areas probably contain a large diversity of GABAA receptors. In many areas, a consistent coexpression was observed for alpha 1 and beta 2 mRNAs, which often colocalized with gamma 2 mRNA. The alpha 1 beta 2 combination was abundant in olfactory bulb, globus pallidus, inferior colliculus, substantia nigra pars reticulata, globus pallidus, zona incerta, subthalamic nucleus, medial septum, and cerebellum. Colocalization was also apparent for the alpha 2 and beta 3 mRNAs, and these predominated in areas such as amygdala and hypothalamus. The alpha 3 mRNA occurred in layers V and VI of neocortex and in the reticular thalamic nucleus. In much of the forebrain, with the exception of hippocampal pyramidal cells, the alpha 4 and delta transcripts appeared to codistribute. In thalamic nuclei, the only abundant GABAA receptor mRNAs were those of alpha 1, alpha 4, beta 2, and delta. In the medial geniculate thalamic nucleus, alpha 1, alpha 4, beta 2, delta, and gamma 3 mRNAs were the principal GABAA receptor transcripts. The alpha 5 and beta 1 mRNAs generally colocalized and may encode predominantly hippocampal forms of the GABAA receptor. These anatomical observations support the hypothesis that alpha 1 beta 2 gamma 2 receptors are responsible for benzodiazepine I (BZ I) binding, whereas receptors containing alpha 2, alpha 3, and alpha 5 contribute to subtypes of the BZ II site. Based on significant mism
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.