The Experts below are selected from a list of 6240 Experts worldwide ranked by ideXlab platform
Miao Jing - One of the best experts on this subject based on the ideXlab platform.
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rapid multi directed Cholinergic Transmission in the central nervous system
Nature Communications, 2021Co-Authors: Santhosh Sethuramanujam, Miao Jing, Michael J Mcintosh, Akihiro Matsumoto, David M Berson, Keisuke Yonehara, Geoff Derosenroll, Benjamin L Murphybaum, Claudio Grosman, Gautam B AwatramaniAbstract:In many parts of the central nervous system, including the retina, it is unclear whether Cholinergic Transmission is mediated by rapid, point-to-point synaptic mechanisms, or slower, broad-scale ‘non-synaptic’ mechanisms. Here, we characterized the ultrastructural features of Cholinergic connections between direction-selective starburst amacrine cells and downstream ganglion cells in an existing serial electron microscopy data set, as well as their functional properties using electrophysiology and two-photon acetylcholine (ACh) imaging. Correlative results demonstrate that a ‘tripartite’ structure facilitates a ‘multi-directed’ form of Transmission, in which ACh released from a single vesicle rapidly (~1 ms) co-activates receptors expressed in multiple neurons located within ~1 µm of the release site. Cholinergic signals are direction-selective at a local, but not global scale, and facilitate the transfer of information from starburst to ganglion cell dendrites. These results suggest a distinct operational framework for Cholinergic signaling that bears the hallmarks of synaptic and non-synaptic forms of Transmission. Cholinergic neurons may transmit information via fast synaptic, point-to-point signaling or diffuse, slow extra-synaptic signaling. The authors show that ACh from a single vesicle triggers synchronous miniature currents in two neurons, showing that ACh can spread significant distances to drive rapid ‘synaptic’ signals.
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rapid multi directed Cholinergic Transmission at central synapses
bioRxiv, 2020Co-Authors: Santhosh Sethuramanujam, Miao Jing, Michael J Mcintosh, Akihiro Matsumoto, David M Berson, Keisuke Yonehara, Gautam B AwatramaniAbstract:Abstract Acetylcholine (ACh) is a key neurotransmitter that plays diverse roles in many parts of the central nervous system, including the retina. However, assessing the precise spatiotemporal dynamics of ACh is technically challenging and whether ACh transmits signals via rapid, point-to-point synaptic mechanisms, or broader-scale ‘non-synaptic’ mechanisms has been difficult to ascertain. Here, we examined the properties of Cholinergic Transmission at individual contacts made between direction-selective starburst amacrine cells and downstream ganglion cells in the retina. Using a combination of electrophysiology, serial block-face electron microscopy, and two-photon ACh imaging, we demonstrate that ACh signaling bears the hallmarks of both non-synaptic and synaptic forms of Transmission. ACh co-activates nicotinic ACh receptors located on the intersecting dendrites of pairs of ganglion cells, with equal efficiency (non-synaptic)— and yet retains the ability to generate rapid ‘miniature’ currents (∼1 ms rise times: synaptic). Fast Cholinergic signals do not appear to depend on anatomically well-defined synaptic structures. We estimate that ACh spread is limited to ∼1-2 µm from its sites of release, which may help starbursts drive local direction-selective Cholinergic responses in ganglion cell dendrites. Together, our results establish the functional architecture for Cholinergic signaling at a central synapse and propose a novel motif whereby single presynaptic sites can co-transmit information to multiple neurons on a millisecond timescale.
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a genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies
Nature Biotechnology, 2018Co-Authors: Miao Jing, Peijun Zhang, Guangfu Wang, Jiesi Feng, Lukas MesikAbstract:The neurotransmitter acetylcholine (ACh) regulates a diverse array of physiological processes throughout the body. Despite its importance, Cholinergic Transmission in the majority of tissues and organs remains poorly understood owing primarily to the limitations of available ACh-monitoring techniques. We developed a family of ACh sensors (GACh) based on G-protein-coupled receptors that has the sensitivity, specificity, signal-to-noise ratio, kinetics and photostability suitable for monitoring ACh signals in vitro and in vivo. GACh sensors were validated with transfection, viral and/or transgenic expression in a dozen types of neuronal and non-neuronal cells prepared from multiple animal species. In all preparations, GACh sensors selectively responded to exogenous and/or endogenous ACh with robust fluorescence signals that were captured by epifluorescence, confocal, and/or two-photon microscopy. Moreover, analysis of endogenous ACh release revealed firing-pattern-dependent release and restricted volume Transmission, resolving two long-standing questions about central Cholinergic Transmission. Thus, GACh sensors provide a user-friendly, broadly applicable tool for monitoring Cholinergic Transmission underlying diverse biological processes.
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a genetically encoded fluorescent acetylcholine indicator
bioRxiv, 2018Co-Authors: Miao Jing, Peijun Zhang, Guangfu Wang, Haochen Jiang, Lukas Mesik, Jiesi FengAbstract:Acetylcholine (ACh) regulates a diverse array of physiological processes throughout the body, yet Cholinergic Transmission in the majority of tissues/organs remains poorly understood due primarily to the limitations of available ACh-monitoring techniques. We developed a family of G-protein-coupled receptor activation-based ACh sensors (GACh) with sensitivity, specificity, signal-to-noise ratio, kinetics and photostability suitable for monitoring ACh signals in vitro and in vivo. GACh sensors were validated with transfection, viral and/or transgenic expression in a dozen types of neuronal and non-neuronal cells prepared from several animal species. In all preparations, GACh sensors selectively responded to exogenous and/or endogenous ACh with robust fluorescence signals that were captured by epifluorescent, confocal and/or two-photon microscopy. Moreover, analysis of endogenous ACh release revealed firing pattern-dependent release and restricted volume Transmission, resolving two long-standing questions about central Cholinergic Transmission. Thus, GACh sensors provide a user-friendly, broadly applicable toolbox for monitoring Cholinergic Transmission underlying diverse biological processes.
Susan J Birren - One of the best experts on this subject based on the ideXlab platform.
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Satellite glial cells modulate Cholinergic Transmission between sympathetic neurons.
PloS one, 2020Co-Authors: Joana Enes, Marian Haburcak, Surbhi Sona, Nega Gerard, Alexander C. Mitchell, Susan J BirrenAbstract:Postganglionic sympathetic neurons and satellite glial cells are the two major cell types of the peripheral sympathetic ganglia. Sympathetic neurons project to and provide neural control of peripheral organs and have been implicated in human disorders ranging from cardiovascular disease to peripheral neuropathies. Here we show that satellite glia regulate synaptic activity of cultured postnatal sympathetic neurons, providing evidence for local ganglionic control of sympathetic drive. In addition to modulating neuron-to-neuron Cholinergic neuroTransmission, satellite glia promote synapse formation and contribute to neuronal survival. Examination of the cellular architecture of the rat sympathetic ganglia in vivo shows this regulation of neuronal properties takes place during a developmental period in which neuronal morphology and density are actively changing and satellite glia enwrap sympathetic neuronal somata. Cultured satellite glia make and release factors that promote neuronal activity and that can partially rescue the neurons from cell death following nerve growth factor deprivation. Thus, satellite glia play an early and ongoing role within the postnatal sympathetic ganglia, expanding our understanding of the contributions of local and target-derived factors in the regulation of sympathetic neuron function.
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Satellite glial cells modulate Cholinergic Transmission between sympathetic neurons
2019Co-Authors: Joana Enes, Marian Haburcak, Surbhi Sona, Nega Gerard, Alexander C. Mitchell, Susan J BirrenAbstract:Abstract Postganglionic sympathetic neurons and satellite glial cells are the two major cell types of the peripheral sympathetic ganglia. Sympathetic neurons project to and provide neural control of peripheral organs and have been implicated in human disorders ranging from cardiovascular disease to peripheral neuropathies. Here we show that satellite glia regulate postnatal development and activity of sympathetic neurons, providing evidence for local ganglionic control of sympathetic drive. We show changes in the cellular architecture of the rat sympathetic ganglia during the postnatal period, with satellite glia enwrapping sympathetic neuronal somata during a period of neuronal hypertrophy. In culture, satellite glia contribute to neuronal survival, promote synapse formation and play a modulatory role in neuron-to-neuron Cholinergic neuroTransmission, consistent with the close contact seen within the ganglia. Cultured satellite glia make and release neurotrophins, which can partially rescue the neurons from nerve growth factor deprivation. Electrophysiological recordings and immunocytochemical analysis on cultured sympathetic neurons show that satellite glial cells influence synapse number and total neuronal activity with little effect on neuronal intrinsic excitability. Thus, satellite glia play an early and ongoing role within the postnatal sympathetic ganglia, expanding our understanding of the contributions of local and target-derived factors in the regulation of sympathetic neuron function.
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a rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor
Nature Neuroscience, 2002Co-Authors: Bo Yang, John D Slonimsky, Susan J BirrenAbstract:Cardiac function is modulated by norepinephrine release from innervating sympathetic neurons. These neurons also form excitatory connections onto cardiac myocytes in culture. Here we report that brain-derived neurotrophic factor (BDNF) altered the neurotransmitter release properties of these sympathetic neuron-myocyte connections in rodent cell culture, leading to a rapid shift from excitatory to inhibitory Cholinergic Transmission in response to neuronal stimulation. Fifteen minutes of BDNF perfusion was sufficient to cause this shift to inhibitory Transmission, indicating that BDNF promotes preferential release of acetylcholine in response to neuronal stimulation. We found that p75−/− neurons did not release acetylcholine in response to BDNF and that neurons overexpressing p75 showed increased Cholinergic Transmission, indicating that the actions of BDNF are mediated through the p75 neurotrophin receptor. Our findings indicate that p75 is involved in modulating the release of distinct neurotransmitter pools, resulting in a functional switch between excitatory and inhibitory neuroTransmission in individual neurons.
Daniel Dautan - One of the best experts on this subject based on the ideXlab platform.
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Segregated Cholinergic Transmission in the ventral tegmental area
2020Co-Authors: Daniel Dautan, Albert Souza, Icnelia Huerta-ocampo, Miguel Valencia, Maxime Assous, Ilana B Witten, Karl Deisseroth, James Tepper, Paul J Bolam, Todor V GerdjikovAbstract:Abstract Dopamine neurons in the ventral tegmental area (VTA) receive Cholinergic innervation from brainstem structures associated with either movement or reward. While Cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. Here we used optogenetic methods combined with in vivo juxtacellular recording and labeling to dissect the influence of brainstem Cholinergic innervation of distinct subpopulations of neurons in the VTA. We found that LDT Cholinergic axons selectively enhance the bursting activity of mesolimbic dopamine neurons that are excited by aversive stimulation. In contrast, PPN Cholinergic axons activate and change the discharge properties of VTA neurons that are integrated in distinct functional circuits and are inhibited by aversive stimulation. While both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of Cholinergic Transmission operate in the VTA and segregate neurons involved in different reward circuits.
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Cholinergic midbrain afferents modulate striatal circuits and shape encoding of action strategies
2020Co-Authors: Daniel Dautan, Icnelia Huerta-ocampo, Miguel Valencia, Todor V Gerdjikov, Nadine K Gut, Krishnakanth Kondabolu, Yuwoong Kim, Juan Mena-segoviaAbstract:Assimilation of novel strategies into a consolidated action repertoire is a crucial function for behavioral adaptation and cognitive flexibility. Acetylcholine in the striatum plays a pivotal role in such adaptation, and its release has been causally associated with the activity of Cholinergic interneurons. Here we show that the midbrain, a previously unknown source of acetylcholine in the striatum, is a major contributor to Cholinergic Transmission in the striatal complex. Neurons of the pedunculopontine and laterodorsal tegmental nuclei synapse with striatal Cholinergic interneurons and give rise to excitatory responses. Furthermore, they produce uniform inhibition of spiny projection neurons. Inhibition of acetylcholine release from midbrain terminals in the striatum impairs the association of contingencies and the formation of habits in an instrumental task, and mimics the effects observed following inhibition of acetylcholine release from striatal Cholinergic interneurons. These results suggest the existence of two hierarchically-organized modes of Cholinergic Transmission in the striatum, where Cholinergic interneurons are modulated by Cholinergic neurons of the midbrain
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segregated Cholinergic Transmission modulates dopamine neurons integrated in distinct functional circuits
Nature Neuroscience, 2016Co-Authors: Daniel Dautan, Miguel Valencia, Maxime Assous, Albert Schiaveto De Souza, Icnelia Huertaocampo, Ilana B WittenAbstract:Dopamine neurons in the ventral tegmental area (VTA) receive Cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas Cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem Cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT Cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN Cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of Cholinergic Transmission operate in the VTA and segregate the neurons involved in different reward circuits.
Maxime Assous - One of the best experts on this subject based on the ideXlab platform.
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striatal Cholinergic Transmission focus on nicotinic receptors influence in striatal circuits
European Journal of Neuroscience, 2021Co-Authors: Maxime AssousAbstract:The critical role of acetylcholine (ACh) in the basal ganglia is evident from the effect of Cholinergic agents in patients suffering from several related neurological disorders, such as Parkinson's disease, Tourette syndrome, or dystonia. The striatum possesses the highest density of ACh markers in the basal ganglia underlying the importance of ACh in this structure. Striatal Cholinergic interneurons (CINs) are responsible for the bulk of striatal ACh, although extrinsic Cholinergic afferents from brainstem structures may also play a role. CINs are tonically active, and synchronized pause in their activity occurs following the presentation of salient stimuli during behavioral conditioning. However, the synaptic mechanisms involved are not fully understood in this physiological response. ACh modulates striatal circuits by acting on muscarinic and nicotinic receptors existing in several combinations both presynaptically and postsynaptically. While the effects of ACh in the striatum through muscarinic receptors have received particular attention, nicotinic receptors function has been less studied. Here, after briefly reviewing relevant results regarding muscarinic receptors expression and function, I will focus on striatal nicotinic receptor expressed presynaptically on glutamatergic and dopaminergic afferents and postsynaptically on diverse striatal interneurons populations. I will also review recent evidence suggesting the involvement of different GABAergic sources in two distinct nicotinic-receptor-mediated striatal circuits: the disynaptic inhibition of striatal projection neurons and the recurrent inhibition among CINs. A better understanding of striatal nicotinic receptors expression and function may help to develop targeted pharmacological interventions to treat brain disorders such as Parkinson's disease, Tourette syndrome, dystonia, or nicotine addiction.
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Segregated Cholinergic Transmission in the ventral tegmental area
2020Co-Authors: Daniel Dautan, Albert Souza, Icnelia Huerta-ocampo, Miguel Valencia, Maxime Assous, Ilana B Witten, Karl Deisseroth, James Tepper, Paul J Bolam, Todor V GerdjikovAbstract:Abstract Dopamine neurons in the ventral tegmental area (VTA) receive Cholinergic innervation from brainstem structures associated with either movement or reward. While Cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. Here we used optogenetic methods combined with in vivo juxtacellular recording and labeling to dissect the influence of brainstem Cholinergic innervation of distinct subpopulations of neurons in the VTA. We found that LDT Cholinergic axons selectively enhance the bursting activity of mesolimbic dopamine neurons that are excited by aversive stimulation. In contrast, PPN Cholinergic axons activate and change the discharge properties of VTA neurons that are integrated in distinct functional circuits and are inhibited by aversive stimulation. While both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of Cholinergic Transmission operate in the VTA and segregate neurons involved in different reward circuits.
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segregated Cholinergic Transmission modulates dopamine neurons integrated in distinct functional circuits
Nature Neuroscience, 2016Co-Authors: Daniel Dautan, Miguel Valencia, Maxime Assous, Albert Schiaveto De Souza, Icnelia Huertaocampo, Ilana B WittenAbstract:Dopamine neurons in the ventral tegmental area (VTA) receive Cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas Cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem Cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT Cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN Cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of Cholinergic Transmission operate in the VTA and segregate the neurons involved in different reward circuits.
Fabio Buttari - One of the best experts on this subject based on the ideXlab platform.
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treatment with dimethyl fumarate enhances Cholinergic Transmission in multiple sclerosis
CNS Drugs, 2019Co-Authors: Carolina Gabri Nicoletti, Doriana Landi, Fabrizia Monteleone, Giorgia Mataluni, Maria Albanese, Benedetta Lauretti, Camilla Rocchi, Ilaria Simonelli, Laura Boffa, Fabio ButtariAbstract:Dimethyl fumarate (DMF) exerts anti-inflammatory effects in multiple sclerosis by activating the Nrf2 antioxidant pathway, which is also stimulated by acetylcholine via alpha-7 nicotinic acetylcholine receptors. In animal models, Nrf2 potentiates Cholinergic synaptic plasticity. The aim of this study was to test whether treatment with DMF modulates Cholinergic pathways in relapsing-remitting multiple sclerosis (RRMS). Patients starting DMF (20) or IFN-β 1a (20) and healthy subjects (20) were enrolled. Short-latency afferent inhibition (SAI), which is a transcranial stimulation measure of central Cholinergic Transmission, was recorded in patients and controls at baseline and, in patients only, after 6 months of treatment. Patients treated with DMF also underwent autonomic function testing to further explore peripheral and central Cholinergic tone. At baseline, SAI was similar in patients and in controls (p = 0.983). Treatment with DMF significantly increased SAI (p = 0.01), while IFNβ had no effect (p = 0.80). In the cold face test, DMF treatment also increased reflex bradycardia (p = 0.013), and reduced diastolic blood pressure variation (p = 0.010), further indicating its ability to stimulate Cholinergic Transmission. Treatment of MS patients with DMF results in increased Cholinergic stimulation, with possible implications for neuroinflammation and neuroprotection.