gabaergic synaptic appositions: Topics by WorldWideScience.org

Maturation of GABAergic Inhibition Promotes Strengthening of Temporally Coherent Inputs among Convergent Pathways

Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion....Full Text Available

2010-05-12

Unraveling mechanisms of homeostatic synaptic plasticity

Spike-timing-dependent plasticity (STDP), a form of Hebbian plasticity, is inherently stabilizing. Whether and how GABAergic inhibition influences STDP is not well understood. Using a model neuron driven by converging inputs modifiable by STDP, we determined that a sufficient level of inhibition was critical to ensure that temporal coherence (correlation among presynaptic spike times) of synaptic inputs, rather than initial strength or number of inputs within a pathway, controlled postsynaptic spike timing. Inhibition exerted this effect by preferentially reducing synaptic efficacy, the ability of inputs to evoke postsynaptic action potentials, of the less coherent inputs. In visual cortical slices, inhibition potently reduced synaptic efficacy at ages during but not before the critical period of ocular dominance (OD) plasticity. Whole-cell recordings revealed that the amplitude of unitary IPSCs from ...

2010-06-03

Maturation of GABAergic Inhibition Promotes Strengthening of Temporally Coherent Inputs among Convergent Pathways

SUMMARYHomeostatic synaptic plasticity is a negative feedback mechanism neurons use to offset excessive excitation or inhibition by adjusting their synaptic strengths. Recent...Full Text Available

2010-05-13

Tweek, an evolutionary conserved proteinis required for synaptic vesicle recycling

2010-06-01

Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity.

Synaptic vesicle endocytosis is critical to maintain synaptic communication during intense stimulation. Here we describe Tweek, a conserved protein that is required for synaptic vesicle recycling....Full Text Available

2009-07-30

DEFF Research Database (Denmark)

Udgivelsesdato: 2007-Feb

2007-01-01

Prenatal cocaine reduces AMPA receptor synaptic expression through hyperphosphorylation of the synaptic anchoring protein GRIP

Emotional enhancement of memory: how norepinephrine enables synaptic plasticity

Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic...Full Text Available

2009-05-13

The Arc of synaptic memory

Changes in synaptic strength are believed to underlie learning and memory. We explore the idea that norepinephrine is an essential modulator of memory through its ability to regulate synaptic mechanisms....Full Text Available

Defective Glycinergic Synaptic Transmission in Zebrafish Motility Mutants

The immediate early gene Arc is emerging as a versatile, finely tuned system capable of coupling changes in neuronal activity patterns to synaptic plasticity, thereby optimizing information...Full Text Available

2010-01-01

Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration

Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using...Full Text Available

Heterogeneity of the supramammillary-hippocampal pathways: Evidence for a unique GABAergic neurotransmitter phenotype and regional differences

The pleiotropic actions of neuromodulators on pre- and postsynaptic targets present challenges to disentangling the mechanisms underlying regulation of synaptic transmission. Within the striatum,...Full Text Available

2009-09-01

Granule cells in the CA3 area

The supramammillary nucleus (SuM) provides substantial projections to the hippocampal formation. This hypothalamic structure is involved in the regulation of hippocampal theta rhythm and therefore...Full Text Available

2010-09-01

Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT

A fundamental property of neuronal networks in Ammon’s horn is that each area is comprised of a single glutamatergic cell population and various types of GABAergic neurons. Here we describe...Full Text Available

2010-06-16

A Comparative Perspective on Minicolumns and Inhibitory GABAergic Interneurons in the Neocortex

γ-Aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in...Full Text Available

2010-07-01

Synaptic Signaling and Aberrant RNA Splicing in Autism Spectrum Disorders

Neocortical columns are functional and morphological units whose architecture may have been under selective evolutionary pressure in different mammalian lineages in response to encephalization and specializations...Full Text Available

Selective Excitatory Actions of DNQX and CNQX in Rat Thalamic Neurons

Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing...Full Text Available

Long-term synaptic transformation of hippocampal CA1 gamma-aminobutyric acid synapses and the effect of anandamide.

The thalamic reticular nucleus (TRN) consists of GABA-containing neurons that form reciprocal synaptic connections with thalamic relay nuclei. Excitatory synaptic innervation of TRN neurons arises from...Full Text Available

2010-04-01

Intrinsic plasticity complements LTP in parallel fiber input gain control in cerebellar Purkinje cells

Evidence is presented for a distinctive type of hippocampal synaptic modification [previously described for a molluscan gamma-aminobutyric acid (GABA) synapse after paired pre- and postsynaptic excitation]:...Full Text Available

1995-10-24

Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in...Full Text Available

2010-10-13

Microfluidic local perfusion chambers for the visualization and manipulation of synapses

Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms ...

1990-02-26

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Dynamic clamp with StdpC software

SummaryThe polarized nature of neurons as well as the size and density of synapses complicates the manipulation and visualization of cell biological processes that control synaptic...Full Text Available

2010-04-15

Dynamic Clamp Analysis of Synaptic Integration in Sympathetic Ganglia

Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based...Full Text Available

2011-03-01

Association and expression study of synapsin III and schizophrenia

Advances in modern neuroscience require the identification of principles that connect different levels of experimental analysis, from molecular mechanisms to explanations of cellular functions,...Full Text Available

2007-11-01

AMPA-receptor trafficking and injury-induced cell death

The synapsin III gene, SYN3, which belongs to the family of synaptic vesicle-associated proteins, has been implicated in the modulation of neurotransmitter...Full Text Available

2009-11-20

Single Particle Tracking of ?7 Nicotinic AChR in Hippocampal Neurons Reveals Regulated Confinement at Glutamatergic and GABAergic Perisynaptic Sites

AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the...Full Text Available

2010-07-01

Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses

α7 neuronal nicotinic acetylcholine receptors (α7-nAChR) form Ca²⁺-permeable homopentameric channels modulating cortical network activity and cognitive processing....Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Although cognitive performance in humans and experimental animals can be improved by administering omega-3 fatty acid docosahexaenoic acid (DHA), the neurochemical mechanisms underlying this effect remain uncertain. In general, nutrients or drugs that modify brain function or behavior do so by affecting synaptic transmission, usually by changing the quantities of particular neurotransmitters present within synaptic clefts or by acting directly on neurotransmitter receptors or signal-transduction molecules. We find that DHA also affects synaptic transmission in mammalian brain. Brain cells of gerbils or rats receiving this fatty acid manifest increased levels of phosphatides and of specific presynaptic or postsynaptic proteins. They also exhibit increased numbers of dendritic spines on post...

2008-01-01

Time-Dependent Expression of Arc and Zif268 after Acquisition of Fear Conditioning

Progression of Neuronal and Synaptic Remodeling in the rd10 Mouse Model of Retinitis Pigmentosa

Memory consolidation requires transcription and translation of new protein. Arc, an effector immediate early gene, and zif268, a regulatory transcription factor, have been implicated in synaptic plasticity...Full Text Available

2010-01-01

Oligodendrocyte-Myelin Glycoprotein and Nogo Negatively Regulate Activity-Dependent Synaptic Plasticity

The Pde6b^rd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa...Full Text Available

2010-06-01

New insights into purinergic receptor signaling in neuronal differentiation, neuroprotection, and brain disorders

In the adult mammalian CNS, the growth inhibitors oligodendrocyte-myelin glycoprotein (OMgp) and the reticulon RTN4 (Nogo) are broadly expressed in oligodendrocytes and neurons. Nogo and OMgp...Full Text Available

2010-09-15

Insulin receptor signaling in the development of neuronal structure and function

Ionotropic P2X and metabotropic P2Y purinergic receptors are expressed in the central nervous system and participate in the synaptic process particularly associated with acetylcholine, GABA, and glutamate...Full Text Available

2007-09-01

Dynamin-dependent NMDAR endocytosis during LTD and its dependence on synaptic state

Sensory experience plays a crucial role in regulating neuronal shape and in developing synaptic contacts during brain formation. These features are required for a neuron to receive, integrate, and transmit...Full Text Available

Development of rat CA1 neurones in acute Versus organotypic slices: role of experience in synaptic morphology and activity

BackgroundThe N-methyl-D-aspartate (NMDA)-type glutamate receptor expressed at excitatory glutamatergic synapses is required for learning and memory and is critical for normal brain...Full Text Available

Association of Protein Phosphatase 1?₁ with Spinophilin Suppresses Phosphatase Activity in a Parkinson Disease Model*

Despite their wide use, the physiological relevance of organotypic slices remains controversial. Such cultures are prepared at 5 days postnatal. Although some local circuitry remains intact, they develop...Full Text Available

2003-07-01

A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity

Sustained nigrostriatal dopamine depletion increases the serine/threonine phosphorylation of multiple striatal proteins that play a role in corticostriatal synaptic plasticity, including Thr²⁸⁶...Full Text Available

2008-05-23

A History of Spike-Timing-Dependent Plasticity

Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term...Full Text Available

2010-02-01

Effects of epidermal growth factor on bone formation and resorption in vivo

How learning and memory is achieved in the brain is a central question in neuroscience. Key to today’s research into information storage in the brain is the concept of synaptic plasticity, a...Full Text Available

Targeting the nicotinic alpha7 acetylcholine receptor to enhance cognition in disease

The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at ...

1990-02-01

British Library Electronic Table of Contents (United Kingdom)

A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...

2011-01-01

GABAB Receptors Modulate NMDA Receptor Calcium Signals in Dendritic Spines

British Library Electronic Table of Contents (United Kingdom)

Summary Metabotropic GABAB receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABAB receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABAB r...

2010-01-01

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Detection of behavioral alterations and learning deficits in mice lacking synaptophysin

British Library Electronic Table of Contents (United Kingdom)

The integral membrane protein synaptophysin is one of the most abundant polypeptide components of synaptic vesicles. It is not essential for neurotransmission despite its abundance but is believed to modulate the efficiency of the synaptic vesicle cycle. Detailed behavioral analyses were therefore performed on synaptophysin knockout mice to test whether synaptophysin affects higher brain functions. We find that these animals are more exploratory than their wild type counterparts examining novel objects more closely and intensely in an enriched open field arena. We also detect impairments in learning and memory, most notably reduced object novelty recognition and reduced spatial learning. These deficits are unlikely caused by impaired vision, since all electroretinographic parameters measur...

2009-01-01

Suppressive effects of cadmium on neurons and affected proteins in cultured developing cortical cells

NMR analysis of the structure of synaptobrevin and of its interaction with syntaxin

The purpose of the present study was to examine the in vitro effects of low-dose cadmium (Cd) on developing cortical cells. The cortical cells removed from fetuses (embryonic day 15) were treated with 10 nM of Cd for 24 h. The effects of Cd on dendritic and synaptic development were immunocytochemically observed with anti-microtubule associated protein-2 (MAP2) and anti-synapsin I antibodies, respectively. Administration of Cd suppressed dendritic as well as synaptic development at 10 nM. By two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometric (LC/MS/MS) analysis, we identified three proteins with different expression after Cd-treatment; dihydropyrimidinase-related protein 2 (DRP-2/CRMP-2), 14-3-3-epsillon and calmodulin (CaM). Though the number of identified proteins was small, these proteins are known to be involved in neuronal development. The present study demonstrated the morphological effects as well as ...

2008-11-20

Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease

Synaptobrevin is a synaptic vesicle protein that has an essential role in exocytosis and forms the SNARE complex with syntaxin and SNAP-25. We have analyzed the structure of isolated synaptobrevin and its binary interaction with syntaxin using NMR spectroscopy. Our results demonstrate that isolated synaptobrevin is largely unfolded in solution. The entire SNARE motif of synaptobrevin is capable of interacting with the isolated C-terminal SNARE motif of syntaxin but only a few residues bind to the full-length cytoplasmic region of syntaxin. This result suggests an interaction between the N- and C-terminal regions of syntaxin that competes with core complex assembly.

1999-07-15

British Library Electronic Table of Contents (United Kingdom)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...

2011-01-01

Spike-train bifurcation scaling in two coupled chaotic neurons

Short-term synaptic plasticity in the auditory brain stem by using in-vivo-like stimulation parameters

We investigate the variation of the out-of-phase periodic rhythm produced by two chaotic neurons {bold (}Hindmarsh-Rose neurons [J. L. Hindmarsh and R. M. Rose, Proc. R. Soc. London B {bold 221}, 87 (1984)]{bold )} coupled by electrical and reciprocally synaptic connections. The exploration of a two-parametric bifurcation diagram, as a function of the strength of the electrical and inhibitory coupling, reveals that the periodic rhythms associated to the limit cycles bounded by saddle-node bifurcations, undergo a strong variation as a function of small changes of electrical coupling. We found that there is a scaling law for the bifurcations of the limit cycles as a function of the strength of both couplings. From the functional point of view of this mixed typed of coupling, the small variation of electrical coupling provides a high sensitivity for period regulation inside the regime of out-of-phase synchronization. {copyright} {ital 1997} {ital The American Physical ...

1997-03-01

British Library Electronic Table of Contents (United Kingdom)

Reduced systems such as brain slices offer a powerful approach to study the physiology of auditory neurons in great detail. However, when studying auditory nuclei in reduced systems such as brain slices, especially highly active auditory brain stem nuclei, one has to be aware that the unphysiological lack of activity in the reduced system compared to the in-vivo situation has a number of important effects on the neurons under investigation, and thus on the data that are measured. Most importantly, the lack of chronic activity in the slice preparation has important effects on the properties of short-term plasticity of the synapses. The main purpose of this article is to discuss how spontaneous activity in auditory neurons, or the lack thereof, can affect the data measured.

2011-01-01

Response variability in balanced cortical networks

DEFF Research Database (Denmark)

We study the spike statistics of neurons in a network with dynamically balanced excitation and inhibition. Our model, intended to represent a generic cortical column, comprises randomly connected excitatory and inhibitory leaky integrate-and-fire neurons, driven by excitatory input from an external population. The high connectivity permits a mean field description in which synaptic currents can be treated as gaussian noise, the mean and autocorrelation function of which are calculated self-consistently from the firing statistics of single model neurons. Within this description, a wide range of Fano factors is possible. We find that the irregularity of spike trains is controlled mainly by the strength of the synapses relative to the difference between the firing threshold and the postfiring reset level of the membrane potential. For moderately strong synapses, we find spike statistics very similar to those observed in primary visual cortex.

2006-01-01

Pulsed Radiofrequency Ablation for Residual and Phantom Limb Pain: A Case Series

British Library Electronic Table of Contents (United Kingdom)

Abstract Residual limb pain (RLP) and phantom limb pain (PLP) can be debilitating and can prevent functional gains following amputation. High correlations have been reported between RLP and the stump neuromas following amputation. Many treatment methods including physical therapy, medications, and interventions, have been used with limited success. Pulsed radiofrequency ablation (PRFA) has shown promise in treating neuropathic pain because of the inhibition of evoked synaptic activity. We present 4 amputees who were treated with PRFA after failing conservative management for their RLP and PLP. All 4 patients underwent PRFA and demonstrated at least 80% relief of RLP for over 6 months. One patient reported a complete resolution of phantom sensation while another patient had significantly de...

2010-01-01

GFAP in health and disease

British Library Electronic Table of Contents (United Kingdom)

Glial fibrillary acidic protein (GFAP) is the main intermediate filament protein in mature astrocytes, but also an important component of the cytoskeleton in astrocytes during development. Major recent developments in astrocyte biology and the discovery of novel intermediate filament functions enticed the interest in the function of GFAP. The discovery of various GFAP splice variants gave an additional boost to explore this protein in more detail.The structural role of GFAP in astrocytes has been widely accepted for a long time, but over the years, GFAP has been shown to be involved in astrocyte functions, which are important during regeneration, synaptic plasticity and reactive gliosis. Moreover, different subpopulations of astrocytes have been identified, which are likely to have distinc...

2011-01-01

Association study of SNAP25 and schizophrenia in Irish family and case-control samples

British Library Electronic Table of Contents (United Kingdom)

SNAP25 occurs on chromosome 20p12.2, which has been linked to schizophrenia in some samples, and recently linked to latent classes of psychotic illness in our sample. SNAP25 is crucial to synaptic functioning, may be involved in axonal growth and dendritic sprouting, and its expression may be decreased in schizophrenia. We genotyped 18 haplotype-tagging SNPs in SNAP25 in a sample of 270 Irish high-density families. Single marker and haplotype analyses were performed in FBAT and PDT. We adjusted for multiple testing by computing q values. Association was followed up in an independent sample of 657 cases and 411 controls. We tested for allelic effects on the clinical phenotype by using the method of sequential addition and 5 factor-derived scores of the OPCRIT. Nine of 18 SNPs had P values <...

2010-01-01

Association and expression study of synapsin III and schizophrenia

British Library Electronic Table of Contents (United Kingdom)

The synapsin III gene, SYN3, which belongs to the family of synaptic vesicle-associated proteins, has been implicated in the modulation of neurotransmitter release and in synaptogenesis, suggesting a potential role in several neuropsychiatric diseases. The human SYN3 gene is located on chromosome 22q12-13, a candidate region implicated in previous linkage studies of schizophrenia. However, association studies of SYN3 and schizophrenia have produced inconsistent results. In this study, four SYN3 SNPs (rs133945 (-631 C>G), rs133946 (-196 G>A), rs9862 and rs1056484) were tested in three sets of totally 3759 samples that comprise 655 affected subjects and 626 controls in the Irish Case-Control Study of Schizophrenia (ICCSS), 1350 samples incorporating 273 pedigrees in the Irish Study of High D...

2009-01-01

A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in a-synuclein transgenic C. elegans

British Library Electronic Table of Contents (United Kingdom)

Mutations or multiplications in a-synuclein gene cause familial forms of Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild-type a-synuclein as LB occurs as a hallmark lesion of these disorders, collectively referred to as synucleinopathies, implicating a-synuclein in the pathogenesis of synucleinopathy. To identify modifier genes of a-synuclein-induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg worms) that overexpress human a-synuclein in a pan-neuronal manner. To enhance the RNAi effect in neurons, we crossed a-synuclein Tg worms with an RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to nervous system or synaptic functions, and identified 10 genes that, upon knockdown, caused severe growth/motor abnormalit...

2008-01-01

Generation of human cortical neurons from a new immortal fetal neural stem cell line

Differential diagnosis of rheumatic diseases; Differenzialdiagnose rheumatischer Erkrankungen

Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as ...

2007-02-01

Separation of recycling and reserve synaptic vesicles from cholinergic nerve terminals of the myenteric plexus of guinea pig ileum.

Which imaging modalities are appropriate for the Differential diagnosis of Rheumatic diseases. MRI has far most the highest sensitivity and is unequaled in its brilliant presentation of Anatomy and Pathology. But it is sometimes forgotten, that this is at least in part the result of carefully selected sequences, dedicated to the expected result. In a method totally independent of any result, this should not be the case. In contrary this method should be highly standardised and regardless what will be the findings. This is true for Plain X-ray. It will be shown, that already the outer silhouette of the soft parts with different features of swelling, and differences in density and even more - defects or appositions of the bony silhouette in the majority of cases at least will allow to classify the patient for a group of diseases and in many cases will lead to a definite diagnosis. Differential diagnoses like Rheumatoid Arthritis versus Psoriatic Arthritis or simply ...

2006-05-15

SLC9A9 mutations, gene expression, and protein-protein interactions in rat models of attention-deficit/hyperactivity disorder

Acetylcholine-rich synaptic vesicles were isolated from myenteric plexus-longitudinal muscle strips derived from the guinea pig ileum by the method of Dowe, Kilbinger, and Whittaker [J. Neurochem. 35, 993-1003 (1980)] using either unstimulated preparations or preparations field-stimulated at 1 Hz for 10 min using pulses of 1 ms duration and 10 V . cm-1 intensity. The organ bath contained either tetradeuterated (d4) choline (50 microM) or [3H]acetate (2 muCi . ml-1); d4 acetylcholine was measured by gas chromatography-mass spectrometry. As with Torpedo electromotor cholinergic vesicle preparations made under similar conditions the distribution of newly synthesized (d4 or [3H]) acetylcholine in the zonal gradient from stimulated preparations was not identical with that of endogenous (d0, [1H]) acetylcholine, but corresponded to a subpopulation of denser vesicles (equivalent to the VP2 fraction from Torpedo) that had preferentially taken up newly synthesized ...

1985-01-01

British Library Electronic Table of Contents (United Kingdom)

Abstract SLC9A9 (solute carrier family 9, member 9, also known as Na+/H+ exchanger member (NHE9)) is a membrane protein that regulates the luminal pH of the recycling endosome, an essential organelle for synaptic transmission and plasticity. SLC9A9 has been implicated in human attention deficit hyperactivity disorder (ADHD) and in rat studies of hyperactivity. We examined the SLC9A9 gene sequence and expression profile in prefrontal cortex, dorsal striatum and hippocampus in two genetic rat models of ADHD. We report two mutations in a rat model of inattentive ADHD, the WKY/NCrl rat, which affect the interaction of SLC9A9 with calcineurin homologous protein (CHP). We observed an age-dependent abnormal expression of SLC9A9 in brains of this inattentive model and in the Spontaneous Hypertensi...

2011-01-01

Pet's research at the SHFJ, Cea, one example: development and validation of a radioligand for the study of the cerebral dopaminergic system; La recherche en TEP au SHFJ, CEA. Un exemple: developpement et validation de radioligands pour l'etude du systeme dopaminergique

Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates

The aim of this work is the evaluation of biodistribution and radiation dosimetry of a cocaine analog, the N-(3-iodo-prop-2E-enyl)-2beta-carbo-methoxy-3beta-(4-methyl-phenyl) nor-tropane (PE2I), labeled with carbon 11 ([{sup 11}C]PE2I). The [{sup 11}C]PE2I is a selective radioligand for imaging neuronal dopamine transporter (DAT) with positron emission tomography (PET). The DAT is a membrane-bound pre synaptically located protein that regulates the concentration of dopamine at nerve terminals. DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuro-protective therapeutics and, typically, these studies required several successive PET scans. (author)

2005-10-15

Association study of SNAP25 and schizophrenia in Irish family and case-control samples.

Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional ...

2004-07-15

The noradrenergic system in cultured aggregates of fetal rat brain cells: morphology of the aggregates and pharmacological indices of noradrenergic neurons

2010-03-01

The neuronal nicotinic acetylcholine receptor {alpha}7 subunit gene: Cloning, mapping, structure, and targeting in mouse

Spherical aggregates formed rapidly in culture by re-aggregation of trypsin-dissociated brain cells from the 17-day-old fetal rat. Over about 10 days an initially random distribution of cells evolved into a 3-layered arrangement; cells with characteristics of neurons were found largely in the intermediate layer. The survival of neuronal and glial cell types was evaluated histologically and verified by electron microscopy, which revealed synaptic and myelin structures that rapidly increased in number after 18 days in culture. Levels of norepinephrine (NE) and dopamine (DA) reached peaks of 9.5 and 4.4 ng/mg protein, respectively, at culture day 21. Uptake of ["3H]NE paralleled these amine levels and was blocked by desipramine or pretreatment with either reserpine or 6-OH-DA. Autoradiographs of aggregates labeled with ["3H]NE showed a high density of silver grains over cells, apparently neurons, with branching processes traced for 120 #mu#m. Previously accumulated ...

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Regulation of NMDA and AMPA receptors during the maturation phase of chicken brain development

The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. Using an interspecies ...

1994-09-01

Kainate-enhanced release of D-(3H)aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital

Full text: The maturation of chicken forebrain is protracted and occurs well after synapse formation providing a good model for studying mechanisms of brain maturation. Using microslices from immature (10 day) and adult chicken forebrain prepared after decapitation, we have examined functional properties of NMDA and AMPA receptors by measuring agonist-induced uptake of "4"5Ca"2"+ . The rate and extent of NMDA induced "4"5Ca"2"+ accumulation decreased during maturation with no change in EC_5_0. The rate and extent of the AMPA induced response also decreased with a 60-fold increase in EC_5_0. However, the total NMDA receptor content did not change as indicated by 3 H-MK801 binding and NR1 immunoreactivity in P2 fractions. Similarly, there was no change in the B_m_a_x of "3H-AMPA, though there was a two-fold increase in K_D, and little or no change in the immunoreactivity in GluR1, 2, 2/3 or 4. These results suggest that it is the regulation of receptors, their subunit composition and/or ...

2002-02-04

Glial inflammation and neurodegeneration induced by candoxin, a novel neurotoxin from Bungarus candidus venom: global gene expression analysis using microarray.

A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and L-aspartate (L-ASP). ...

1983-06-01

Association and expression study of synapsin III and schizophrenia.

Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal alpha7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC(50) approximately 1muM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level involves ...

2005-11-23

A model of episodic memory: mental time travel along encoded trajectories using grid cells.

2009-09-19