Imperial College London

Prof. William Wisden F. Med. Sci.

Faculty of Natural SciencesDepartment of Life Sciences

Chair in Molecular Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 9744w.wisden Website CV

 
 
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Location

 

401BSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

199 results found

Wisden W, Moss SJ, 1997, gamma-Aminobutyric acid type A receptor subunit assembly and sorting: gene targeting and cell biology approaches, Biochem Soc Trans, Vol: 25, Pages: 820-824, ISSN: 0300-5127

Journal article

Bahn S, Wisden W, 1997, A map of non-NMDA receptor subunit expression in the vertebrate brain derived from in situ hybridization histochemistry., The ionotropic glutamate receptors, Editors: Monaghan, Wenthold, Publisher: Humana Pr Inc, Pages: 149-187, ISBN: 9780896034563

The Ionotropic Glutamate Receptors provides the first detailed survey of the biochemical, physiological, and pharmacological properties of recombinant ...

Book chapter

Korpi ER, Wisden W, Luddens H, 1997, Better cure for anxiety, sleep disorders, epilepsy?/ Battre bot for oro, somnproblem, epilepsi?, Lakartidningen (Swedish Medical Society), Vol: 94, Pages: 3403-3408, ISSN: 0023-7205

Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter, is characterised by rapid effects that are mediated via GABAA, receptors. These receptors are also targets for many drugs including benzodiazepines, barbiturates and general anaesthetics. Recognition of the heterogeneity of GABAA receptors has opened up new possibilities for the development of more selective therapeutic agents. In particular, subtype-specific receptor ligands varying in intrinsic activity are likely to give rise to fewer side effects than do currently available drugs.

Journal article

Korpi ER, Mattila MJ, Wisden W, Luddens Het al., 1997, GABA(A)-receptor subtypes: clinical efficacy and selectivity of benzodiazepine site ligands, Ann Med, Vol: 29, Pages: 275-282, ISSN: 0785-3890

The main inhibitory neurotransmitter receptor of the brain, the gamma-aminobutyric acid type A receptor (GABA[A]), mediates the actions of several classes of clinically important drugs, such as benzodiazepines, barbiturates and general anaesthetics. This review summarizes the current knowledge on how classical benzodiazepines and novel nonbenzodiazepine compounds act on the benzodiazepine site of GABA(A) receptors and on their clinical pharmacology related to anxiolytic, sedative, hypnotic and cognitive effects or side-effects. Partial agonism, receptor subtype selectivity and novel binding sites are discussed as possible strategies to develop new drugs with fewer adverse effects than are seen in the clinical use of benzodiazepines.

Journal article

Grant AL, Wisden W, 1997, Neuron-specific gene expression., Molecular biology of the neuron, Editors: Davies, Morris, Publisher: Oxford University Press, USA, Pages: 67-93, ISBN: 9781859962404

A valuable compendium of comprehensive and up-to-date reviews of neuronal molecularbiology by leading researchers in the field, this book focuses on genetic ...

Book chapter

Herb A, Wisden W, Catania MV, Marechal D, Dresse A, Seeburg PHet al., 1997, Prominent dendritic localization in forebrain neurons of a novel mRNA and its product, dendrin, Mol Cell Neurosc, Vol: 8, Pages: 367-374, ISSN: 1044-7431

A recently cloned rat brain cDNA derives from a novel gene, termed dendrin (DEN), expressed exclusively in forebrain structures, particularly in neocortex, olfactory bulb, hippocampus, caudate-putamen, and limbic system. In these structures, the cognate mRNA is present in neuronal cell bodies and their dendrites, whereas near exclusive dendritic localization is observed for the polypeptide product. In the hippocamus, DEN mRNA is highly expressed in the cell laminae and dendritic layers of the dentate gyrus and CA1 field, but expression is markedly reduced in the CA3 and CA4 areas. The predicted primary structure of the hydrophilic, highly basic 653-amino-acid polypeptide does not suggest a function. The restricted expression and dendritic location are compatible with a role for DEN in synaptic plasticity of central neocortical forebrain neurons.

Journal article

Grant AL, Wisden W, 1997, DNA regions supporting hippocalcin gene expression in cell lines, Brain Res Mol Brain Res, Vol: 52, Pages: 323-325, ISSN: 0169-328X

Journal article

Bahn S, Jones A, Wisden W, 1997, Directing gene expression to cerebellar granule cells using gamma-aminobutyric acid type A receptor alpha6 subunit transgenes, Proc Natl Acad Sci U S A, Vol: 94, Pages: 9417-9421, ISSN: 0027-8424

Journal article

Jones A, Korpi ER, McKernan RM, Pelz R, Nusser Z, Makela R, Mellor JR, Pollard S, Bahn S, Stephenson FA, Randall AD, Sieghart W, Somogyi P, Smith AJ, Wisden Wet al., 1997, Ligand-gated ion channel subunit partnerships: GABA-A receptor alpha6 subunit gene inactivation inhibits delta subunit expression, J Neurosci, Vol: 17, Pages: 1350-1362, ISSN: 0270-6474

Cerebellar granule cells express six GABA-A receptor subunits abundantly (alpha1, alpha6, beta2, beta3, gamma2, and delta) and assemble various pentameric receptor subtypes with unknown subunit compositions; however, the rules guiding receptor subunit assembly are unclear. Here, removal of intact alpha6 protein from cerebellar granule cells allowed perturbations in other subunit levels to be studied. Exon 8 of the mouse alpha6 subunit gene was disrupted by homologous recombination. In alpha6 -/- granule cells, the delta subunit was selectively degraded as seen by immunoprecipitation, immunocytochemistry, and immunoblot analysis with delta subunit-specific antibodies. The delta subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a post-translational loss of the delta subunit. These results provide genetic evidence for a specific association between the alpha6 and delta subunits. Because in alpha6 -/- neurons the remaining alpha1, beta2/3, and gamma2 subunits cannot rescue the delta subunit, certain potential subunit combinations may not be found in wild-type cells.

Journal article

Bahn S, Harvey RJ, Darlison MG, Wisden Wet 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

Journal article

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.

Journal article

Makela R, Lehtonen M, Wisden W, Luddens H, Korpi ERet 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.

Journal article

Jones A, Bahn S, Grant AL, Kohler M, Wisden Wet 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.

Journal article

Grant AL, Jones A, Thomas KL, Wisden Wet 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

Journal article

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

Conference paper

KEMPF HG, BRANDLE TU, WISDEN W, ZENNER HP, MARX Aet 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

Journal article

Kempf HG, Brändle TU, Wisden W, Zenner HP, Marx Aet 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.

Journal article

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

Journal article

Tolle TR, Berthele A, Zieglgansberger W, Seeburg PH, Wisden Wet 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.

Journal article

Hunt SP, McNaughton LA, Jenkins R, Wisden Wet 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

Book chapter

KEMPF HG, BRANDLE TU, WISDEN W, ZENNER HPet 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

Journal article

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.

Book

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.

Book chapter

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.

Book chapter

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

Journal article

Schoepfer R, Monyer H, Sommer B, Wisden W, Sprengel R, Kuner T, Lomeli H, Herb A, Kohler M, Burnashev N, Gunther G, Ruppersberg P, Seeburg PHet 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.

Book chapter

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

Journal article

Lomeli H, Sprengel R, Laurie DJ, Kohr G, Herb A, Seeburg PH, Wisden Wet 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.

Journal article

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.

Journal article

Wisden W, Parker EM, Mahle CD, Grisel DA, Nowak HP, Yocca FD, Felder CC, Seeburg PH, Voigt MMet 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.

Journal article

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