Central somatostatin systems revealed with monoclonal antibodies

Vincent, Steven R.; McIntosh, C. H. S.; Buchan, A.M.J.; Brown, John C.

doi:10.1002/cne.902380205

Cited by 261 publications

(119 citation statements)

References 98 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…These can be distinguished from cholinergic neurons by their smaller size (Di Figlia and Aronin, 1982), even in the ventral striatum (Vincent et al, 1985) and we concentrate our study on the larger neurons. In the dual labeling study, most of the large neurons immunoreactive for NR2D subunits were also immunolabeled with ChAT.…”

Section: Discussionmentioning

confidence: 99%

Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl-d-aspartate 2D but not N-methyl-d-aspartate 2C receptor subunits

et al. 2007

View full text Add to dashboard Cite

Cholinergic neurons of the striatum play a crucial role in controlling output from this region. Their firing is under the control of a relatively limited glutamatergic input, deriving principally from the thalamus. Glutamate transmission is effected via three major subtypes of receptors, including those with affinity for N-methyl-D-aspartate (NMDA) and the properties of individual receptors reflect their precise subunit composition. We examined the distribution of NMDA2C and NMDA2D subunits in the rat striatum using immunocytochemistry and show that a population of large neurons is strongly immunoreactive for NMDA2D subunits. From their morphology and ultrastructure, these neurons were presumed to be cholinergic and this was confirmed with double immunofluorescence. We also show that NMDA2C is present in a small number of septal and olfactory cortical neurons but absent from the striatum.Receptors that include NMDA2D subunits are relatively insensitive to magnesium ion block making neurons more likely to fire at more negative membrane potentials. Their localization to cholinergic neurons may enable very precise regulation of firing of these neurons by relatively small glutamatergic inputs. Keywordsinterneuron; ultrastructure; synapse; endoplasmic reticulumThe cholinergic neurons of the striatum play an important role in basal ganglia control of voluntary movement. They represent only 1-2% of striatal neurons but their extensive local axon collateral system, innervating both medium-sized densely spiny neurons (MSN) (Izzo and Bolam, 1988) and other local circuit neurons (Koos and Tepper, 2002) is consistent with a primary role in determining the final activity of striatal output neurons (Calabresi et al., 2000). While the majority of glutamatergic input to MSN originates in the cortical regions, excitatory input to these tonically active, cholinergic striatal neurons comes almost exclusively from the parafascicular thalamic nucleus (Lapper and Bolam, 1992;Zhou et al., 2002) and possibly from the cortex (Thomas et al., 2000), and principally from the midline/intralaminar thalamic nuclei to the ventral striatum (Meredith and Wouterlood, 1990 The firing of cholinergic neurons is under the control of a relatively few inputs and interactions are subserved by a number of different glutamate receptor subtypes. Although no AMPA subunits have been reported (Chen et al., 1996;Fujiyama et al., 2004), cholinergic neurons express kainate GluR5, 6 and 7 subunits (Chen et al., 1996). Moreover, stimulation of metabotropic receptor subunits, mGluR1-3, 5 and 7 (Bell et al., 2002) exerts a profound effect on cell excitability (Di Chiara et al., 1994). In addition, N-methyl-D-aspartate (NMDA) agonists potentiate striatal acetylcholine release (Giovannini et al., 1995) while direct stimulation of the thalamostriatal pathway increases acetylcholine release, via action on N-methyl-D-aspartate receptors (NR) (Consolo et al., 1996). Double labeling studies combining in situ hybridization for subunit mRNA with immunolabeling with a...

show abstract

Section: Discussionmentioning

confidence: 99%

Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl-d-aspartate 2D but not N-methyl-d-aspartate 2C receptor subunits

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In the hypothalamus, IDX1/IPF1 is present at a time of active neurogenesis (reviewed in Ref. 20) in regions that generate neurons for several nuclei, including those with the highest number of somatostatin-expressing cells (periventricular, suprachiasmatic, and arcuate nuclei and anterolateral hypothalamus) (43,53).…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Homeodomain Transcription Factor IDX1/IPF1 Expressed in Developing Brain Regulates Somatostatin Gene Transcription in Embryonic Neural Cells

Schwartz¹,

Pérez-Villamil²,

Rivera³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hox-like homeodomain proteins play a critical role during embryonic development by regulating the transcription of genes that are important for the generation of specific organs or cell types. The homeodomain transcription factor IDX1/IPF1, the expression of which was thought until recently to be restricted to the pancreas and foregut, is required for pancreas development and for the expression of genes controlling glucose homeostasis. We report that IDX1/IPF1 is also expressed in embryonic rat brain at a time coincident with active neurogenesis. Electrophoretic mobility shift assays with nuclear extracts of embryonic brains indicated that IDX1/IPF1 binds to two somatostatin promoter elements, SMS-UE-B and the recently discovered SMS-TAAT3. The requirement of these elements for IDX1/ IPF1 transactivation of the somatostatin gene in neural cells was confirmed in transfection studies using embryonic cerebral cortex-derived RC2.E10 cells. Immunohistochemical staining of rat embryos showed IDX1/IPF1-positive cells located near the ventricular surface in germinative areas of the developing central nervous system. Cellular colocalization of IDX1/IPF1 and somatostatin was found in several areas of the developing brain, including cortex, ganglionic eminence, hypothalamus, and inferior colliculus. These results support the notion that IDX1/IPF1 regulates gene expression during development of the central nervous system independent of its role on pancreas development and function.Homeodomain genes encode a large family of transcription factors that are grouped in different classes, including, for example, Hox-, POU-, Pax-, LIM-, and Dlx-like proteins, depending on the relative degree of conservation of the homeodomain. During gestation, expression of individual homeodomain genes is critical for proper regional development of the central nervous system (CNS) 1 and peripheral tissues of the embryo. IDX1/IPF1 (also known as STF-1 and PDX-1) is a transcription factor encoded by a Hox-like homeodomain gene, the expression of which was initially described to be restricted to the pancreas and duodenum, and it has been demonstrated that pancreas development requires IDX1/IPF1 in mice (1, 2). This requirement was confirmed in the human by the identification of an individual with pancreatic agenesis and a homozygous mutation in the IPF-1 gene (3). In addition, IDX1/IPF1 is essential for normal pancreatic islet function by regulating the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, and glucose transporter type 2 (4 -8). Importantly, in humans, heterozygous mutations of the IPF-1 gene are linked to a type of autosomal dominant diabetes mellitus known as maturity onset diabetes of the young (MODY4) (9).In the developing neural tube, different homeodomain genes that control mechanisms of regional and cellular determination are selectively expressed in the primordia of the three major regions of the CNS: forebrain, midbrain, and hindbrain (10). In the hindbrain, certain Hox-like ...

show abstract

“…All secondary antibodies were purchased from commercial sources (Table 1), as well as several primary antibodies: mouse antivasoactive intestinal polypeptide (VIP) and rabbit anti-calretinin (CR) from Biogenesis (Poole, UK); rabbit anti-VIP from Euro-diagnostica (Boldon, UK); rat anti-muscarinic type 2 receptor (M2) and guinea pig anti-substance P receptor (NK1) from Chemicon (Chandlers Ford, UK); rabbit anti-mGluR1a from DiaSorin (Stillwater, MN); mouse antiparvalbumin (PV) from Sigma-Aldrich (Gillingham, UK); and rabbit anti-calbindin (CB-38, lot 5.5), mouse anti-CR, and mouse and rabbit anti-PV from Swant (Bellinzona, Switzerland). Other primary antibodies were kindly provided by the following: Dr. A. Buchan (Medical Research Council Regulatory Peptide Group, Vancouver, British Columbia, Canada), mouse anti-somatostatin (SOM) (Vincent et al, 1985); Dr. K. Tanaka (Niigata University, Niigata, Japan), human anti-glutamic acid decarboxylase (GAD) (Oe et al, 1996); Dr A. Varro (Liverpool University, Liverpool, UK), rabbit anti-procholecystokinin (CCK) (Morino et al, 1994); Dr. K.G. Baimbridge (University of British Columbia, Vancouver, British Columbia, Canada), guinea pig anti-PV ; Dr. J. Polak (Imperial College, London, UK), rabbit antineuropeptide Y (NPY) (Allen et al, 1983); and Dr. B. Gasnier (Centre National de la Recherche Scientifique-Institut de Biologie PhysicoChimique, Paris, France), rabbit anti-vesicular GABA transporter (VI-AAT) (Dumoulin et al, 1999).…”

Section: Methodsmentioning

confidence: 99%

Metabotropic Glutamate Receptor 8-Expressing Nerve Terminals Target Subsets of GABAergic Neurons in the Hippocampus

Ferraguti¹,

Klausberger²,

Cobden³

et al. 2005

J. Neurosci.

121

138

View full text Add to dashboard Cite

Presynaptic metabotropic glutamate receptors (mGluRs) show a highly selective expression and subcellular location in nerve terminals modulating neurotransmitter release. We have demonstrated that alternatively spliced variants of mGluR8, mGluR8a and mGluR8b, have an overlapping distribution in the hippocampus, and besides perforant path terminals, they are expressed in the presynaptic active zone of boutons making synapses selectively with several types of GABAergic interneurons, primarily in the stratum oriens. Boutons labeled for mGluR8 formed either type I or type II synapses, and the latter were GABAergic. Some mGluR8-positive boutons also expressed mGluR7 or vasoactive intestinal polypeptide. Interneurons strongly immunopositive for the muscarinic M2 or the mGlu1 receptors were the primary targets of mGluR8-containing terminals in the stratum oriens, but only neurochemically distinct subsets were innervated by mGluR8-enriched terminals. The majority of M2-positive neurons were mGluR8 innervated, but a minority, which expresses somatostatin, was not. Rare neurons coexpressing calretinin and M2 were consistently targeted by mGluR8-positive boutons. In vivo recording and labeling of an mGluR8-decorated and strongly M2-positive interneuron revealed a trilaminar cell with complex spike bursts during theta oscillations and strong discharge during sharp wave/ripple events. The trilaminar cell had a large projection from the CA1 area to the subiculum and a preferential innervation of interneurons in the CA1 area in addition to pyramidal cell somata and dendrites. The postsynaptic interneuron type-specific expression of the high-efficacy presynaptic mGluR8 in both putative glutamatergic and in identified GABAergic terminals predicts a role in adjusting the activity of interneurons depending on the level of network activity.

show abstract

Central somatostatin systems revealed with monoclonal antibodies

Cited by 261 publications

References 98 publications

Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl-d-aspartate 2D but not N-methyl-d-aspartate 2C receptor subunits

Cholinergic neurons of the adult rat striatum are immunoreactive for glutamatergic N-methyl-d-aspartate 2D but not N-methyl-d-aspartate 2C receptor subunits

Pancreatic Homeodomain Transcription Factor IDX1/IPF1 Expressed in Developing Brain Regulates Somatostatin Gene Transcription in Embryonic Neural Cells

Metabotropic Glutamate Receptor 8-Expressing Nerve Terminals Target Subsets of GABAergic Neurons in the Hippocampus

Contact Info

Product

Resources

About