The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Nicholas C Spitzer - One of the best experts on this subject based on the ideXlab platform.
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mechanism for Neurotransmitter Receptor matching
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Dena R Hammondweinberger, Yunxin Wang, Alex Glavisbloom, Nicholas C SpitzerAbstract:Synaptic communication requires the expression of functional postsynaptic Receptors that match the presynaptically released Neurotransmitter. The ability of neurons to switch the transmitter they release is increasingly well documented, and these switches require changes in the postsynaptic Receptor population. Although the activity-dependent molecular mechanism of Neurotransmitter switching is increasingly well understood, the basis of specification of postsynaptic Neurotransmitter Receptors matching the newly expressed transmitter is unknown. Using a functional assay, we show that sustained application of glutamate to embryonic vertebrate skeletal muscle cells cultured before innervation is necessary and sufficient to up-regulate ionotropic glutamate Receptors from a pool of different Receptors expressed at low levels. Up-regulation of these ionotropic Receptors is independent of signaling by metabotropic glutamate Receptors. Both imaging of glutamate-induced calcium elevations and Western blots reveal ionotropic glutamate Receptor expression prior to immunocytochemical detection. Sustained application of glutamate to skeletal myotomes in vivo is necessary and sufficient for up-regulation of membrane expression of the GluN1 NMDA Receptor subunit. Pharmacological antagonists and morpholinos implicate p38 and Jun kinases and MEF2C in the signal cascade leading to ionotropic glutamate Receptor expression. The results suggest a mechanism by which neuronal release of transmitter up-regulates postsynaptic expression of appropriate transmitter Receptors following Neurotransmitter switching and may contribute to the proper expression of Receptors at the time of initial innervation.
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implications of activity dependent Neurotransmitter Receptor matching
Philosophical Transactions of the Royal Society B, 2008Co-Authors: Nicholas C Spitzer, Laura N BorodinskyAbstract:Electrical activity has numerous roles in early neuronal development. Calcium transients generated at low frequencies regulate neural induction and neuronal proliferation, migration and differentiation. Recent work demonstrates that these signals participate in specification of the transmitters expressed in different classes of neurons. Matching of postsynaptic Receptor expression with the novel expression of transmitters ensues. These findings have intriguing implications for development, mature function and evolution of the nervous system.
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activity dependent Neurotransmitter Receptor matching at the neuromuscular junction
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Laura N Borodinsky, Nicholas C SpitzerAbstract:Signaling in the nervous system requires matching of Neurotransmitter Receptors with cognate Neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine Receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification in embryonic spinal neurons, we hypothesized that Receptor expression in postsynaptic cells follows changes in transmitter expression to achieve this specific match. We find that embryonic vertebrate striated muscle cells normally express Receptors for glutamate, GABA, and glycine as well as for acetylcholine. As maturation progresses, acetylcholine Receptor expression prevails. Receptor selection is altered when early neuronal calcium-dependent activity is perturbed, and remaining Receptor populations parallel changes in transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic synaptic currents are recorded from muscle cells, demonstrating that activity regulates matching of transmitters and their Receptors in the assembly of functional synapses.
Daniel Choquet - One of the best experts on this subject based on the ideXlab platform.
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measurement and characteristics of Neurotransmitter Receptor surface trafficking review
Molecular Membrane Biology, 2008Co-Authors: Laurent Groc, Daniel ChoquetAbstract:Neurotransmitter Receptor trafficking in and out synapses has emerged as a key process to regulate synaptic transmission during synaptic development and plasticity both at excitatory and inhibitory synapses. Lateral diffusion of surface Neurotransmitter Receptors has recently emerged as a key pathway to regulate Receptor trafficking to and from synapses. Receptors enter and exit synapses mainly by lateral diffusion within the plane of the membrane while their retrieval and addition from and to the plasma membrane by endo and exocytotic processes occur largely at extrasynaptic sites. As a consequence, regulation of Receptor surface trafficking is likely to be a major process to regulate Receptor numbers at synapses. Measurement of Receptor surface diffusion has required the development of new experimental approaches to specifically label and track surface Receptor with appropriate time- and space-resolutions. In this review, we first discuss the approaches that have been used to measure Receptor surface di...
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Surface trafficking of membrane proteins at excitatory and inhibitory synapses
Structural And Functional Organization Of The Synapse, 2008Co-Authors: Daniel Choquet, Antoine TrillerAbstract:Neurotransmitter Receptor trafficking in and out synapses has emerged as a key process to regulate synaptic transmission both at excitatory and inhibitory synapses. Receptors enter and exit synapses mainly by lateral diffusion within the plane of the membrane while their retrieval and addition from and to the plasma membrane by endo and exocytotic proc- esses occur largely at extrasynaptic sites. As a consequence, regulation of Receptor surface trafficking is likely to be a major process to regulate Receptor numbers at synapses. We will here review the current knowledge on the molecular mechanisms that control both excitatory and inhibitory Receptors diffusion in the plasma membrane. We will present and compare the different imaging approaches that have allowed to measure Receptor diffusion from the bulk down to the single molecule levels. The concepts that have emerged from single molecule imaging in neuroscience will be discussed.
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Measurement and characteristics of Neurotransmitter Receptor surface trafficking (Review)
Molecular Membrane Biology, 2008Co-Authors: Laurent Groc, Daniel ChoquetAbstract:Neurotransmitter Receptor trafficking in and out synapses has emerged as a key process to regulate synaptic transmission during synaptic development and plasticity both at excitatory and inhibitory synapses. Lateral diffusion of surface Neurotransmitter Receptors has recently emerged as a key pathway to regulate Receptor trafficking to and from synapses. Receptors enter and exit synapses mainly by lateral diffusion within the plane of the membrane while their retrieval and addition from and to the plasma membrane by endo and exocytotic processes occur largely at extrasynaptic sites. As a consequence, regulation of Receptor surface trafficking is likely to be a major process to regulate Receptor numbers at synapses. Measurement of Receptor surface diffusion has required the development of new experimental approaches to specifically label and track surface Receptor with appropriate time- and space-resolutions. In this review, we first discuss the approaches that have been used to measure Receptor surface diffusion, such as the ensemble approach that measure average diffusion of a defined surface Receptor population and the single molecule/particle approaches that measure the surface diffusion of isolated Receptors. To date, surface diffusion has been described for a variety of Neurotransmitter Receptors that exhibit common as well as specific features. These points are discussed in a comparative manner and emerging rules of surface trafficking as well as potential interplay between Receptor classes are further commented. Because our knowledge on Neurotransmitter Receptor surface diffusion is fairly recent, open questions and experimental challenges facing the field are highlighted throughout the review.
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Surface Trafficking of Membrane Proteins at Excitatory and Inhibitory Synapses 2 Evidence and Necessity for Excitatory and Inhibitory Receptors to Diffuse on the Neuron Surface
Receptor, 2008Co-Authors: Daniel Choquet, Antoine TrillerAbstract:Abstract. Neurotransmitter Receptor trafficking in and out synapses has emerged as a key process to regulate synaptic transmission both at excitatory and inhibitory synapses. Receptors enter and exit synapses mainly by lateral diffusion within the plane of the membrane while their retrieval and addition from and to the plasma membrane by endo and exocytotic proc- esses occur largely at extrasynaptic sites. As a consequence, regulation of Receptor surface trafficking is likely to be a major process to regulate Receptor numbers at synapses. We will here review the current knowledge on the molecular mechanisms that control both excitatory and inhibitory Receptors diffusion in the plasma membrane. We will present and compare the different imaging approaches that have allowed to measure Receptor diffusion from the bulk down to the single molecule levels. The concepts that have emerged from single molecule imaging in neuroscience will be discussed.
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surface trafficking of Neurotransmitter Receptor comparison between single molecule quantum dot strategies
The Journal of Neuroscience, 2007Co-Authors: Laurent Groc, Mari Anne Renner, Victor Racine, Jean-Baptiste Sibarita, Mathieu Lafourcade, Daniel Choquet, Brahim Lounis, Martin Heine, Laurent CognetAbstract:The cellular traffic of Neurotransmitter Receptors has captured a lot of attention over the last decade, mostly because synaptic Receptor number is adjusted during synaptic development and plasticity. Although each Neurotransmitter Receptor family has its own trafficking characteristics, two main
Karl Zilles - One of the best experts on this subject based on the ideXlab platform.
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acetylcholine Neurotransmitter Receptor densities in the striatum of hemiparkinsonian rats following botulinum neurotoxin a injection
Frontiers in Neuroanatomy, 2018Co-Authors: Teresa Mann, Karl Zilles, Nicola Palomerogallagher, Markus Cremer, Felix Klawitter, Alexander Hawlitschka, Oliver Schmitt, Andreas WreeAbstract:: Cholinergic neurotransmission has a pivotal function in the caudate-putamen, and is highly associated with the pathophysiology of Parkinson's disease. Here, we investigated long-term changes in the densities of the muscarinic Receptor subtypes M1, M2, M3 (mAchRs) and the nicotinic Receptor subtype α4β2 (nAchRs) in the striatum of the 6-OHDA-induced hemiparkinsonian (hemi-PD) rat model using quantitative in vitro Receptor autoradiography. Hemi-PD rats exhibited an ipsilateral decrease in striatal mAchR densities between 6 and 16%. Moreover, a massive and constant decrease in striatal nAchR density by 57% was found. A second goal of the study was to disclose Receptor-related mechanisms for the positive motor effect of intrastriatally injected Botulinum neurotoxin-A (BoNT-A) in hemi-PD rats in the apomorphine rotation test. Therefore, the effect of intrastriatally injected BoNT-A in control and hemi-PD rats on mAchR and nAchR densities was analyzed and compared to control animals or vehicle-injected hemi-PD rats. BoNT-A administration slightly reduced interhemispheric differences of mAchR and nAchR densities in hemi-PD rats. Importantly, the BoNT-A effect on striatal nAchRs significantly correlated with behavioral testing after apomorphine application. This study gives novel insights of 6-OHDA-induced effects on striatal mAchR and nAchR densities, and partly explains the therapeutic effect of BoNT-A in hemi-PD rats on a cellular level.
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common molecular basis of the sentence comprehension network revealed by Neurotransmitter Receptor fingerprints
Cortex, 2015Co-Authors: Karl Zilles, Nicola Palomerogallagher, Katrin Amunts, Maraike Bachatrams, Angela D FriedericiAbstract:The language network is a well-defined large-scale neural network of anatomically and functionally interacting cortical areas. The successful language process requires the transmission of information between these areas. Since Neurotransmitter Receptors are key molecules of information processing, we hypothesized that cortical areas which are part of the same functional language network may show highly similar multiReceptor expression pattern (“Receptor fingerprint”), whereas those that are not part of this network should have different fingerprints. Here we demonstrate that the relation between the densities of 15 different excitatory, inhibitory and modulatory Receptors in eight language-related areas are highly similar and differ considerably from those of 18 other brain regions not directly involved in language processing. Thus, the fingerprints of all cortical areas underlying a large-scale cognitive domain such as language is a characteristic, functionally relevant feature of this network and an important prerequisite for the underlying neuronal processes of language functions.
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Neurotransmitter Receptor density changes in pitx3ak mice a model relevant to parkinson s disease
Neuroscience, 2015Co-Authors: J.n. Cremer, Katrin Amunts, J. Graw, Markus Piel, Frank Rösch, Karl ZillesAbstract:Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by alterations of nigrostriatal dopaminergic neurotransmission. Compared to the wealth of data on the impairment of the dopamine system, relatively limited evidence is available concerning the role of major non-dopaminergic Neurotransmitter systems in PD. Therefore, we comprehensively investigated the density and distribution of Neurotransmitter Receptors for glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine in brains of homozygous aphakia mice being characterized by mutations affecting the Pitx3 gene. This genetic model exhibits crucial hallmarks of PD on the neuropathological, symptomatic and pharmacological level. Quantitative Receptor autoradiography was used to characterize 19 different Receptor binding sites in eleven brain regions in order to understand Receptor changes on a systemic level. We demonstrated striking differential changes of Neurotransmitter Receptor densities for numerous Receptor types and brain regions, respectively. Most prominent, a strong up-regulation of GABA Receptors and associated benzodiazepine binding sites in different brain regions and concomitant down-regulations of striatal nicotinic acetylcholine and serotonergic Receptor densities were found. Furthermore, the densities of glutamatergic kainate, muscarinic acetylcholine, adrenergic α 1 and dopaminergic D 2 /D 3 Receptors were differentially altered. These results present novel insights into the expression of Neurotransmitter Receptors in Pitx3 ak mice supporting findings on PD pathology in patients and indicating on the possible underlying mechanisms. The data suggest Pitx3 ak mice as an appropriate new model to investigate the role of Neurotransmitter Receptors in PD. Our study highlights the relevance of non-dopaminergic systems in PD and for the understanding of its molecular pathology.
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Neurotransmitter Receptor density changes in Pitx3ak mice – A model relevant to Parkinson’s disease
Neuroscience, 2014Co-Authors: J.n. Cremer, Katrin Amunts, J. Graw, Markus Piel, Frank Rösch, Karl ZillesAbstract:Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by alterations of nigrostriatal dopaminergic neurotransmission. Compared to the wealth of data on the impairment of the dopamine system, relatively limited evidence is available concerning the role of major non-dopaminergic Neurotransmitter systems in PD. Therefore, we comprehensively investigated the density and distribution of Neurotransmitter Receptors for glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine in brains of homozygous aphakia mice being characterized by mutations affecting the Pitx3 gene. This genetic model exhibits crucial hallmarks of PD on the neuropathological, symptomatic and pharmacological level. Quantitative Receptor autoradiography was used to characterize 19 different Receptor binding sites in eleven brain regions in order to understand Receptor changes on a systemic level. We demonstrated striking differential changes of Neurotransmitter Receptor densities for numerous Receptor types and brain regions, respectively. Most prominent, a strong up-regulation of GABA Receptors and associated benzodiazepine binding sites in different brain regions and concomitant down-regulations of striatal nicotinic acetylcholine and serotonergic Receptor densities were found. Furthermore, the densities of glutamatergic kainate, muscarinic acetylcholine, adrenergic α 1 and dopaminergic D 2 /D 3 Receptors were differentially altered. These results present novel insights into the expression of Neurotransmitter Receptors in Pitx3 ak mice supporting findings on PD pathology in patients and indicating on the possible underlying mechanisms. The data suggest Pitx3 ak mice as an appropriate new model to investigate the role of Neurotransmitter Receptors in PD. Our study highlights the relevance of non-dopaminergic systems in PD and for the understanding of its molecular pathology.
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Neurotransmitter Receptor alterations in hepatic encephalopathy a review
Archives of Biochemistry and Biophysics, 2013Co-Authors: Nicola Palomerogallagher, Karl ZillesAbstract:Abstract Hepatic encephalopathy (HE), a complex neuropsychiatric syndrome with symptoms ranging from subtle neuropsychiatric and motor disturbances to deep coma and death, is thought to be a clinical manifestation of a low-grade cerebral oedema associated with an altered neuron-astrocyte crosstalk and exacerbated by hyperammonemia and oxidative stress. These events are tightly coupled with alterations in neurotransmission, either in a causal or a causative manner, resulting in a net increase of inhibitory neurotransmission. Therefore, research focussed mainly on the potential role of γ-aminobutyric acid-(GABA) or glutamate-mediated neurotransmission in the pathophysiology of HE, though roles for other Neurotransmitters (e.g. serotonin, dopamine, adenosine and histamine) or for neurosteroids or endogenous benzodiazepines have also been suggested. Therefore, we here review HE-related alterations in neurotransmission, focussing on changes in the levels of classical Neurotransmitters and the neuromodulator adenosine, variations in the activity and/or concentrations of key enzymes involved in their metabolism, as well as in the densities of their Receptors.
Laura N Borodinsky - One of the best experts on this subject based on the ideXlab platform.
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implications of activity dependent Neurotransmitter Receptor matching
Philosophical Transactions of the Royal Society B, 2008Co-Authors: Nicholas C Spitzer, Laura N BorodinskyAbstract:Electrical activity has numerous roles in early neuronal development. Calcium transients generated at low frequencies regulate neural induction and neuronal proliferation, migration and differentiation. Recent work demonstrates that these signals participate in specification of the transmitters expressed in different classes of neurons. Matching of postsynaptic Receptor expression with the novel expression of transmitters ensues. These findings have intriguing implications for development, mature function and evolution of the nervous system.
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activity dependent Neurotransmitter Receptor matching at the neuromuscular junction
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Laura N Borodinsky, Nicholas C SpitzerAbstract:Signaling in the nervous system requires matching of Neurotransmitter Receptors with cognate Neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine Receptors are not fully understood. Because alterations in neuronal calcium spike activity alter transmitter specification in embryonic spinal neurons, we hypothesized that Receptor expression in postsynaptic cells follows changes in transmitter expression to achieve this specific match. We find that embryonic vertebrate striated muscle cells normally express Receptors for glutamate, GABA, and glycine as well as for acetylcholine. As maturation progresses, acetylcholine Receptor expression prevails. Receptor selection is altered when early neuronal calcium-dependent activity is perturbed, and remaining Receptor populations parallel changes in transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic synaptic currents are recorded from muscle cells, demonstrating that activity regulates matching of transmitters and their Receptors in the assembly of functional synapses.
Laurent Groc - One of the best experts on this subject based on the ideXlab platform.
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measurement and characteristics of Neurotransmitter Receptor surface trafficking review
Molecular Membrane Biology, 2008Co-Authors: Laurent Groc, Daniel ChoquetAbstract:Neurotransmitter Receptor trafficking in and out synapses has emerged as a key process to regulate synaptic transmission during synaptic development and plasticity both at excitatory and inhibitory synapses. Lateral diffusion of surface Neurotransmitter Receptors has recently emerged as a key pathway to regulate Receptor trafficking to and from synapses. Receptors enter and exit synapses mainly by lateral diffusion within the plane of the membrane while their retrieval and addition from and to the plasma membrane by endo and exocytotic processes occur largely at extrasynaptic sites. As a consequence, regulation of Receptor surface trafficking is likely to be a major process to regulate Receptor numbers at synapses. Measurement of Receptor surface diffusion has required the development of new experimental approaches to specifically label and track surface Receptor with appropriate time- and space-resolutions. In this review, we first discuss the approaches that have been used to measure Receptor surface di...
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Measurement and characteristics of Neurotransmitter Receptor surface trafficking (Review)
Molecular Membrane Biology, 2008Co-Authors: Laurent Groc, Daniel ChoquetAbstract:Neurotransmitter Receptor trafficking in and out synapses has emerged as a key process to regulate synaptic transmission during synaptic development and plasticity both at excitatory and inhibitory synapses. Lateral diffusion of surface Neurotransmitter Receptors has recently emerged as a key pathway to regulate Receptor trafficking to and from synapses. Receptors enter and exit synapses mainly by lateral diffusion within the plane of the membrane while their retrieval and addition from and to the plasma membrane by endo and exocytotic processes occur largely at extrasynaptic sites. As a consequence, regulation of Receptor surface trafficking is likely to be a major process to regulate Receptor numbers at synapses. Measurement of Receptor surface diffusion has required the development of new experimental approaches to specifically label and track surface Receptor with appropriate time- and space-resolutions. In this review, we first discuss the approaches that have been used to measure Receptor surface diffusion, such as the ensemble approach that measure average diffusion of a defined surface Receptor population and the single molecule/particle approaches that measure the surface diffusion of isolated Receptors. To date, surface diffusion has been described for a variety of Neurotransmitter Receptors that exhibit common as well as specific features. These points are discussed in a comparative manner and emerging rules of surface trafficking as well as potential interplay between Receptor classes are further commented. Because our knowledge on Neurotransmitter Receptor surface diffusion is fairly recent, open questions and experimental challenges facing the field are highlighted throughout the review.
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surface trafficking of Neurotransmitter Receptor comparison between single molecule quantum dot strategies
The Journal of Neuroscience, 2007Co-Authors: Laurent Groc, Mari Anne Renner, Victor Racine, Jean-Baptiste Sibarita, Mathieu Lafourcade, Daniel Choquet, Brahim Lounis, Martin Heine, Laurent CognetAbstract:The cellular traffic of Neurotransmitter Receptors has captured a lot of attention over the last decade, mostly because synaptic Receptor number is adjusted during synaptic development and plasticity. Although each Neurotransmitter Receptor family has its own trafficking characteristics, two main
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Surface Trafficking of Neurotransmitter Receptor: Comparison between Single-Molecule/Quantum Dot Strategies
The Journal of Neuroscience, 2007Co-Authors: Laurent Groc, Mari Anne Renner, Victor Racine, Jean-Baptiste Sibarita, Mathieu Lafourcade, Daniel Choquet, Brahim Lounis, Martin Heine, Laurent CognetAbstract:The cellular traffic of Neurotransmitter Receptors has captured a lot of attention over the last decade, mostly because synaptic Receptor number is adjusted during synaptic development and plasticity. Although each Neurotransmitter Receptor family has its own trafficking characteristics, two main
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Surface trafficking of Neurotransmitter Receptor: comparison between single-molecule/quantum dot strategies.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007Co-Authors: Laurent Groc, Mari Anne Renner, Victor Racine, Jean-Baptiste Sibarita, Mathieu Lafourcade, Brahim Lounis, Martin Heine, Daniel ChoquetAbstract:The cellular traffic of Neurotransmitter re- ceptors has captured a lot of attention over the last decade, mostly because syn- aptic Receptor number is adjusted during synaptic development and plasticity. Al- though each Neurotransmitter Receptor family has its own trafficking characteris- tics, two main modes of Receptor delivery to the synapse have emerged: endo- exocytotic cycling and surface diffusion [e.g., for glutamatergic Receptors, see Bredt and Nicoll (2003) and Groc and Choquet (2006)]. Receptor cycling through endo-exocytotic processes can be measured by several experimental means, from biochemical to imaging assays.