Publications
219 results found
Laurie DJ, Wisden W, Seeburg PH, 1992, The distribution of thirteen GABA-A receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development, J Neurosci, Vol: 12, Pages: 4151-4172, ISSN: 0270-6474
The embryonic and postnatal expression of 13 GABAA receptor subunit genes in the rat CNS was studied by in situ hybridization. Each transcript exhibited a unique regional and temporal developmental expression profile. For example, in both embryonic and early postnatal cortex and thalamus, expression of the alpha 2, alpha 3, alpha 5, and beta 3 mRNAs was pronounced. In particular, the alpha 5 gene expression underwent a prominent peak in early brain. Subsequently, the thalamocortical expression of these four genes substantially diminished and was superseded in the adult by the alpha 1, alpha 4, beta 2, and delta subunit mRNAs. Similarly, gamma 1 and gamma 3 gene expression also dropped markedly during development, their initial stronger expression being restricted to relatively few structures. In contrast, gamma 2 gene expression was widespread and mostly remained constant with increasing age. The medial septum and globus pallidus were regions expressing few subunits in both early postnatal and adult stages, allowing clear developmental combinatorial changes to be inferred (alpha 2/alpha 3 beta 2 gamma 2 to alpha 1 beta 2 gamma 2, alpha 2/alpha 3 beta 2 gamma 1 to alpha 1 beta 2 gamma 1/gamma 2, respectively). In contrast, cerebellar Purkinje cells exhibited no developmental switch, expressing only the alpha 1, beta 2, beta 3, and gamma 2 mRNAs from birth to adult. Certain GABAA transcripts were also detected in germinal zones (e.g., beta 1, beta 3, gamma 1) and in embryonic peripheral tissues such as dorsal root ganglia (e.g., alpha 2, alpha 3, beta 3, gamma 2) and intestine (gamma 3). Some parallels in regional and temporal CNS expression were noted (e.g., alpha 1 beta 2, alpha 2 beta 3, alpha 4/alpha 6 delta), whereas the alpha 5 and beta 1 regional mRNA expressions converted over time. The changes of GABAA receptor subunit gene expression suggest a molecular explanation for earlier observations on changing ligand binding affinities. Thus, the composition, and pre
Burnashev N, Khodorova A, Jonas P, et al., 1992, Calcium-permeable AMPA-kainate receptors in fusiform cerebellar glial cells, Science, Vol: 256, Pages: 1566-15770, ISSN: 0036-8075
Glutamate-operated ion channels (GluR channels) of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate subtype are found in both neurons and glial cells of the central nervous system. These channels are assembled from the GluR-A, -B, -C, and -D subunits; channels containing a GluR-B subunit show an outwardly rectifying current-voltage relation and low calcium permeability, whereas channels lacking the GluR-B subunit are characterized by a doubly rectifying current-voltage relation and high calcium permeability. Most cell types in the central nervous system coexpress several subunits, including GluR-B. However, Bergmann glia in rat cerebellum do not express GluR-B subunit genes. In a subset of cultured cerebellar glial cells, likely derived from Bergmann glial cells. GluR channels exhibit doubly rectifying current-voltage relations and high calcium permeability, whereas GluR channels of cerebellar neurons have low calcium permeability. Thus, differential expression of the GluR-B subunit gene in neurons and glia is one mechanism by which functional properties of native GluR channels are regulated.
Herb A, Burnashev N, Werner P, et al., 1992, The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits, Neuron, Vol: 8, Pages: 775-785, ISSN: 0896-6273
A new ionotropic glutamate receptor subunit termed KA-2, cloned from rat brain cDNA, exhibits high affinity for [3H]kainate (KD approximately 15 nM). KA-2 mRNA is widely expressed in embryonic and adult brain. Homomeric KA-2 expression does not generate agonist-sensitive channels, but currents are observed when KA-2 is coexpressed with GluR5 or GluR6 subunits. Specifically, coexpression of GluR5(R) and KA-2 produces channel activity, whereas homomeric expression of either subunit does not. Currents through heteromeric GluR5(Q)/KA-2 channels show more rapid desensitization and different current-voltage relations when compared with GluR5(Q) currents. GluR6/KA-2 channels are gated by AMPA, which fails to gate homomeric GluR6 receptor channels. These results suggest possible in vivo partnership relations for high affinity kainate receptors.
Lomeli H, Wisden W, Kohler M, et al., 1992, High-affinity kainate and domoate receptors in rat brain, FEBS Lett, Vol: 307, Pages: 139-143, ISSN: 0014-5793
Mammalian brain expresses receptors which bind the potent neurotoxins, kainate and domoate, with high affinity, and which form a subclass of ionotropic glutamate receptors. A new member of these receptors, expressed in both adult and embryonic CNS is compared in its ligand binding properties to its closely sequence-related homologs.
Muller F, Greferath U, Wassle H, et al., 1992, Glutamate receptor expression in the rat retina, Neurosci Lett, Vol: 138, Pages: 179-182, ISSN: 0304-3940
The expression of five genes (GluR A; B; C; D; GluR 5) encoding functional subunits of glutamate receptors was investigated in the rat retina using in situ hybridization with oligonucleotide probes. All five genes are expressed in the retina. All probes label cell bodies in the ganglion cell layer as well as somata in the inner third of the inner nuclear layer (INL), where the amacrine cells are located. In addition GluR 5, B and D, and to a lesser extent also GluR A are found in the middle and outer part of the INL, where bipolar and horizontal cells reside. Different subsets of retinal neurons may thus use glutamate receptors of different subunit composition.
Sommer B, Monyer H, Wisden W, et al., 1992, Glutamate-gated ion channels in the brain. Genetic mechanism for generating molecular and functional diversity, Arzneimittelforschung, Pages: 209-210
Luddens H, Wisden W, 1991, Function and pharmacology of multiple GABA-A receptor subunits, Trends Pharmacol Sci, Vol: 12, Pages: 49-51
Wisden W, Gundlach AL, Barnard EA, et al., 1991, Distribution of GABA-A receptor subunit mRNAs in rat lumbar spinal cord, Brain Res Mol Brain Res, Vol: 10, Pages: 179-183, ISSN: 0169-328X
The expression of various GABAA receptor subunit mRNAs (alpha 1, alpha 2, alpha 3, alpha 5, beta 1, beta 2, beta 3, gamma 2, delta) was studied in the adult rat lumbar spinal cord by in situ hybridization. Of these, only alpha 2, alpha 3, beta 3 and gamma 2 mRNAs are expressed at significant levels. The alpha 3, beta 3 and gamma 2 transcripts are present in many neurons throughout the Rexed laminae, whereas the alpha 2 mRNA is restricted to motor neurons and adjacent cells.
Ultsch A, Schuster CM, Betz H, et al., 1991, In situ hybridization with oligonucleotides: a simplified method to detect Drosophila transcripts, Nucleic Acids Res, Vol: 19
Marqueze-Pouey B, Wisden W, Malosio ML, et al., 1991, Differential expression of synaptophysin and synaptoporin mRNAs in the postnatal rat central nervous system, J Neurosci, Vol: 11, Pages: 3388-3397, ISSN: 0270-6474
Synaptophysin and synaptoporin are two homologous integral membrane proteins of small synaptic vesicles. Here, the distribution of the corresponding transcripts in the CNS of the rat was investigated by in situ hybridization using sequence-specific oligonucleotide probes. Synaptophysin mRNA was abundantly distributed through all major brain regions, whereas synaptoporin transcripts displayed a more restricted localization in telencephalic structures. Resolution at the cellular level disclosed a differential labeling of distinct cell types in different areas, suggesting that synaptophysin and synaptoporin are expressed by specific subpopulations of central neurons. Consistent with this conclusion, relative synaptoporin mRNA contents were found to vary between different brain regions during postnatal development, whereas synaptophysin transcripts showed a more uniform increase during the same period.
Bateson AN, Harvey RJ, Wisden W, et al., 1991, The chicken GABA-A receptor alpha 1 subunit: cDNA sequence and localization of the corresponding mRNA, Brain Res Mol Brain Res, Vol: 9, Pages: 333-339, ISSN: 0169-328X
We report the sequence of a complementary DNA (cDNA) that encodes the chicken GABA-A receptor alpha 1 subunit, which is extremely homologous to mammalian alpha 1 subunits. The distribution of alpha 1 subunit transcripts is shown to correlate mainly, but not completely, with the previously-reported pattern of benzodiazepine type I (BZI) binding sites in the avian brain. These results suggest that the alpha 1 subunit may not necessarily be restricted to receptors having BZI pharmacology.
Wisden W, Morris BJ, Hunt SP, 1991, In situ hybridization with synthetic DNA probes., Molecular Neurobiology - A Practical Approach, Editors: Chad, Wheal, Publisher: Oxford University Press/IRL press, Pages: 205-225
Wisden W, Herb A, Wieland H, et al., 1991, Cloning, pharmacological characteristics and expression pattern of the rat GABA-A receptor alpha 4 subunit, FEBS Lett, Vol: 289, Pages: 227-230, ISSN: 0014-5793
A cDNA of rat brain encoding the GABAA receptor alpha 4 subunit has been cloned. Recombinant receptors composed of alpha 4, beta 2 and gamma 2 subunit bind with high affinity the GABA agonist [3H]muscimol and the benzodiazepine 'alcohol antagonist' [3H]Ro 15-4513, but fail to bind benzodiazepine agonists. The alpha 4 subunit is expressed mainly in the thalamus, as assessed by in situ hybridization histochemistry, and may participate in a major population of thalamic GABAA receptors. The alpha 4 mRNA is found at lower levels in cortex and caudate putamen, and is rare in cerebellum.
Werner P, Voigt M, Keinanen K, et al., 1991, Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells, Nature, Vol: 351, Pages: 742-744, ISSN: 0028-0836
Kainic acid is a potent neurotoxin for certain neurons. Its neurotoxicity is thought to be mediated by an excitatory amino-acid-gated ion channel (ionotropic receptor) possessing nanomolar affinity for kainate. Here we describe a new member of the rat excitatory amino-acid receptor gene family, KA-1, that has a 30% sequence similarity with the previously characterized alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D. The pharmacological profile of expressed recombinant KA-1 determined in binding experiments with [3H]kainate is different from that of the cloned AMPA receptors and similar to the mammalian high-affinity kainate receptor (kainate greater than quisqualate greater than glutamate much greater than AMPA) with a dissociation constant of about 5 nM for kainate. The selectively high expression of KA-1 messenger RNA in the CA3 region of the hippocampus closely corresponds to autoradiographically located high-affinity kainate binding sites. This correlation, as well as the particular in vivo pattern of neurodegeneration observed on kainate-induced neurotoxicity, suggests that KA-1 participates in receptors mediating the kainate sensitivity of neurons in the central nervous system.
Monyer H, Seeburg PH, Wisden W, 1991, Glutamate-operated channels: developmentally early and mature forms arise by alternative splicing, Neuron, Vol: 6, Pages: 799-810
The expression of two alternative splice variants, Flip and Flop, in mRNAs encoding the four AMPA-selective glutamate receptors (GluR-A, -B, -C, and -D) was studied in the developing brain by in situ hybridization. These receptors are expressed prominently before birth, and patterns of distribution for Flip versions remain largely invariant during postnatal brain development. In contrast, the Flop versions are expressed at low levels prior to postnatal day 8. Around this time, the expression of Flop mRNAs increases throughout the brain, reaching adult levels by postnatal day 14. Thus, receptors carrying the Flop module appear to participate in mature receptor forms.
Seeburg PH, Wisden W, Pritchett DB, et al., 1991, GABA-A benzodiazepine receptors in the brain: from subunit to subtype., Transmitter Amino Acid Receptors: Structures, Transduction and Models for Drug Development. Fidia Research Foundation Symposium Series, Editors: Barnard, Costa, Publisher: Thieme Verlag, Pages: 13-22
GUNDLACH AL, RUTHERFURD SD, LOUIS WJ, et al., 1990, LOCALIZATION AND MODULATION OF GALANIN MESSENGER-RNA IN RAT-BRAIN - EFFECT OF RESERPINE TREATMENT ON LOCUS-CERULEUS NEURONS, EUROPEAN JOURNAL OF PHARMACOLOGY, Vol: 183, Pages: 496-496, ISSN: 0014-2999
Rusak B, Robertson HA, Wisden W, et al., 1990, Light pulses that shift rhythms induce gene expression in the suprachiasmatic nucleus, Science, Vol: 248, Pages: 1237-1240, ISSN: 0036-8075
Gundlach AL, Wisden W, Morris BJ, et al., 1990, Localization of preprogalanin mRNA in rat brain: in situ hybridization study with a synthetic oligonucleotide probe, Neurosci Lett, Vol: 114, Pages: 241-247, ISSN: 0304-3940
Localization of preprogalanin mRNA in rat brain: in situ hybridization study with a synthetic oligonucleotide probe
SEEBURG PH, WISDEN W, VERDOORN TA, et al., 1990, THE GABA-A RECEPTOR FAMILY - MOLECULAR AND FUNCTIONAL DIVERSITY, SYMP ON THE BRAIN, Publisher: COLD SPRING HARBOR LABORATORY PRESS, Pages: 29-40
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SIRINATHSINGHJI DJS, WISDEN W, NORTHROP A, et al., 1990, CELLULAR-LOCALIZATION OF NEUROTRANSMITTER MESSENGER-RNAS IN STRIATAL GRAFTS, PROGRESS IN BRAIN RESEARCH, Vol: 82, Pages: 433-439, ISSN: 0079-6123
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Sirinathsinghji DJ, Morris BJ, Wisden W, et al., 1990, Gene expression in striatal grafts-I. Cellular localization of neurotransmitter mRNAs, Neuroscience, Vol: 34, Pages: 675-686, ISSN: 0306-4522
his study utilized the technique of in situ hybridization histochemistry to identify cells expressing neurotransmitter mRNAs in embryonic striatal tissue grafts implanted into the ibotenic acid-lesioned rat neostriatum. Synthetic 32P- or 35S-labelled oligodeoxyribonucleotide probes specific for prosomatostatin, proneuropeptide Y. proenkephalin, prodynorphin and preprotachykinin mRNAs and a 32P-labelled cRNA probe specific for glutamate decarboxylase mRNA were used to study the regional and cellular changes in these mRNA levels in the normal, lesioned and grafted neostriatum. The levels of neuropeptide Y mRNA and somatostatin mRNA were substantially increased in the striatal grafts compared with the intact control striata. The levels of glutamate decarboxylase mRNA in the grafts also appeared to be slightly elevated over those in the control striata. However, the levels of proenkephalin mRNA, prodynorphin mRNA and preprotachykinin mRNA were significantly lower in the grafts. The increased levels of neuropeptide Y mRNA and somatostatin mRNA in the grafts were due both to an increase in the number of labelled cells and to an increase in the cellular levels of each neuropeptide mRNA. In contrast, the cellular levels of proenkephalin mRNA, prodynorphin mRNA and preprotachykinin mRNA in the grafts were comparable, or elevated relative, to those in the intact striata but the density of cells expressing each of these mRNAs was reduced. Since neuropeptide Y and somatostatin are known to be present in medium to large aspiny striatal neurons (interneurons) and enkephalin, dynorphin and tachykinin peptides and GABA are localized in medium spiny striatal projection neurons, the above findings would indicate that there is a divergence in the levels of activity between these two neuronal populations in the striatal grafts. Our data suggest that the levels of gene expression and hence the functional neurotransmitter-synthesizing and releasing activity in the grafted neuron are diff
Ymer S, Draguhn A, Wisden W, et al., 1990, Structural and functional characterization of the gamma 1 subunit of GABA-A/benzodiazepine receptors, EMBO J, Vol: 9, Pages: 3261-3267, ISSN: 0261-4189
The GABAA receptor gamma 1 subunit of human, rat and bovine origin was molecularly cloned and compared with the gamma 2 subunit in structure and function. Both gamma subunit variants share 74% sequence similarity and are prominently synthesized in often distinct areas of the central nervous system as documented by in situ hybridization. When co-expressed with alpha and beta subunits in Xenopus oocytes and mammalian cells, the gamma variants mediate the potentiation of GABA evoked currents by benzodiazepines and help generate high-affinity binding sites for these drugs. However, these sites show disparate pharmacological properties which, for receptors assembled from alpha 1, beta 1 and gamma 1 subunits, are characterized by the conspicuous loss in affinity for neutral antagonists (e.g. flumazenil) and negative modulators (e.g. DMCM). These findings reveal a pronounced effect of gamma subunit variants on GABAA/benzodiazepine receptor pharmacology.
Morris BJ, Hicks AA, Wisden W, et al., 1990, Distinct regional expression of nicotinic acetylcholine receptor genes in chick brain, Brain Res Mol Brain Res, Vol: 7, Pages: 305-315, ISSN: 0169-328X
Four genes (alpha 2, alpha 3, alpha 4 and beta 2) have been reported as encoding subunits of the nicotinic acetylcholine receptor (nAChR) in chicken brain. The mRNAs transcribed from these genes have here been localised to particular regions using in situ hybridisation histochemistry. The beta 2 mRNA was clearly the most abundant transcript, being widely distributed throughout the chick brain. In the cerebellum, all four mRNA species were present, although they showed different cellular patterns of distribution. Only alpha 2 mRNA and beta 2 mRNA were found in significant amounts in the optic tectum. In the lateral spiriform nucleus, while alpha 2 mRNA, alpha 4 mRNA and beta 2 mRNA were all very abundant, the alpha 4 mRNA was localised to a subgroup of neurons containing alpha 2 mRNA and beta 2 mRNA. This represents the first evidence that individual cells may express two different nAChR alpha subunit genes in vivo. The distributions of the 4 mRNA species showed few common features. This suggests that other neuronal nAChR genes remain to be identified, and that these 4 genes are not generally expressed in the same cells to constitute a single macromolecular complex. The results therefore provide evidence for nAChR heterogeneity in the central nervous system.
Sirinathsinghji DJ, Wisden W, Northrop A, et al., 1990, Cellular localisation of neurotransmitter mRNAs in striatal grafts, Prog Brain Res, Pages: 433-439
Seeburg PH, Wisden W, Verdoorn TA, et al., 1990, The GABA-A receptor family: molecular and functional diversity, Cold Spring Harb Symp Quant Biol, Vol: 55, Pages: 29-40, ISSN: 0091-7451
Sommer B, Keinanen K, Verdoorn TA, et al., 1990, Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS, Science, Vol: 249, Pages: 1580-1585, ISSN: 0036-8075
In the central nervous system (CNS), the principal mediators of fast synaptic excitatory neurotransmission are L-glutamate-gated ion channels that are responsive to the glutamate agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). In each member of a family of four abundant AMPA receptors, a small segment preceding the predicted fourth transmembrane region has been shown to exist in two versions with different amino acid sequences. These modules, designated "flip" and "flop," are encoded by adjacent exons of the receptor genes and impart different pharmacological and kinetic properties on currents evoked by L-glutamate or AMPA, but not those evoked by kainate. For each receptor, the alternatively spliced messenger RNAs show distinct expression patterns in rat brain, particularly in the CA1 and CA3 fields of the hippocampus. These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.
Wisden W, Errington ML, Williams S, et al., 1990, Differential expression of immediate early genes in the hippocampus and spinal cord, Neuron, Vol: 4, Pages: 603-614, ISSN: 0896-6273
We have demonstrated that immediate early genes can be differentially activated within the central nervous system. We examined the effects of tetanic stimulation in the hippocampus and of noxious sensory stimulation of the spinal cord on the expression of eight immediate early genes. Induction of long-term potentiation (LTP) in the dentate gyrus resulted in an increase in mRNA and protein for NGFI-A (also termed Zif/268, Egr-1, or Krox 24), and less consistently for jun-B mRNA. No increase was seen for c-fos, NGFI-B, c-jun, jun-D, SRF, or PC4 mRNAs. Blockade of the NMDA receptor prevented the induction of both LTP and NGFI-A mRNA in the dentate gyrus. However, commissural stimulation, which prevented the induction of LTP, resulted in bilateral activation of all the genes examined, including NGFI-A. No change was seen in animals trained in a water maze. These results suggest that no simple relationship exists between LTP, spatial learning, and immediate early gene induction. Stimulation of sensory fibers resulted in an increase in mRNA for NGFI-A, c-fos, SRF, NGFI-B, and c-jun in spinal cord neurons. Blockade of the NMDA receptor had no effect on immediate early gene induction in the spinal cord.
Keinanen K, Wisden W, Sommer B, et al., 1990, A family of AMPA-selective glutamate receptors, Science, Vol: 249, Pages: 556-560, ISSN: 0036-8075
Four cloned cDNAs encoding 900-amino acid putative glutamate receptors with approximately 70 percent sequence identity were isolated from a rat brain cDNA library. In situ hybridization revealed differential expression patterns of the cognate mRNAs throughout the brain. Functional expression of the cDNAs in cultured mammalian cells generated receptors displaying alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective binding pharmacology (AMPA = quisqualate greater than glutamate greater than kainate) as well as cation channels gated by glutamate, AMPA, and kainate and blocked by 6,7-dinitroquinoxaline-2,3-dione (CNQX).
WISDEN W, MORRIS BJ, DARLISON MG, et al., 1989, DIFFERENTIAL DISTRIBUTION IN BOVINE BRAIN OF DISTINCT GAMMA-AMINOBUTYRIC ACIDA RECEPTOR ALPHA-SUBUNIT MESSENGER-RNAS, Publisher: PORTLAND PRESS, Pages: 566-567, ISSN: 0300-5127
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