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Cinda J. Helke - One of the best experts on this subject based on the ideXlab platform.
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neurotrophins alter the numbers of neurotransmitter ir mature vagal glossopharyngeal Visceral Afferent neurons in vitro
Brain Research, 2000Co-Authors: Cinda J. Helke, Dominik VerdierpinardAbstract:Abstract Mature nodose and petrosal ganglia neurons (placodally derived Afferent neurons of the vagal and glossopharyngeal nerves) contain TrkA and TrkC, and transport specific neurotrophins [nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)]. This study evaluated neurotrophin influences on the presence of neuropeptides and/or neurotransmitter enzymes in these Visceral sensory neurons. NGF, NT-3 and NT-4 (10–100 ng/ml) were applied (5 days) to dissociated, enriched, cultures of mature nodose/petrosal ganglia neurons, and the neurons processed for tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neurofilament (NF-200) immunocytochemistry. Addition of NGF to nodose/petrosal ganglia neuron-enriched cultures significantly increased the number of TH-immunoreactive (ir) neurons, decreased the number of VIP-ir neurons in the cultures, and did not affect the numbers of CGRP-ir neurons. The addition of an NGF neutralizing antibody attenuated the effects of NGF on TH and VIP-ir neurons. NT-3 increased the number of VIP-ir neurons in the nodose/petrosal ganglia cultures and did not alter the numbers of TH-, or CGRP-ir neurons. The addition of an NT-3 neutralizing antibody attenuated the effects of NT-3 on VIP-ir neurons. NT-4 had no significant effects on the numbers of TH, VIP and CGRP-ir neurons. The absence of neurotrophin-induced changes in the numbers of NF-200-ir neurons in culture showed the lack of neurotrophin-mediated changes in survival of mature vagal Afferent neurons. These data demonstrate that specific neurotrophins influence the numbers of neurons labeled for specific neurochemicals in nodose/petrosal ganglia cultures. These data, coupled with previous evidence for the presence of TrkA and TrkC mRNA and of the retrograde transport of NGF and NT-3, suggest important roles for NGF and NT-3 in the maintenance of transmitter phenotype of these mature Visceral Afferent neurons.
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axonal transport of neurotrophins by Visceral Afferent and efferent neurons of the vagus nerve of the rat
The Journal of Comparative Neurology, 1998Co-Authors: Cinda J. Helke, K M Adryan, J Fedorowicz, H Zhuo, John S Park, Rory A J Curtis, H E Radley, Peter S DistefanoAbstract:The receptor-mediated axonal transport of [125I]-labeled neurotrophins by Afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal Afferent neurons retrogradely transported [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal Afferent neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor specificity of neurotrophin transport was examined by applying [125I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal Afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these Visceral sensory and motor neurons in vivo. J. Comp. Neurol. 393:102–117, 1998. Published 1998 Wiley-Liss, Inc.1
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Axonal transport of neurotrophins by Visceral Afferent and efferent neurons of the vagus nerve of the rat
The Journal of comparative neurology, 1998Co-Authors: Cinda J. Helke, K M Adryan, J Fedorowicz, H Zhuo, John S Park, Rory A J Curtis, H E Radley, Peter S DistefanoAbstract:The receptor-mediated axonal transport of [125I]-labeled neurotrophins by Afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal Afferent neurons retrogradely transported [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal Afferent neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor specificity of neurotrophin transport was examined by applying [125I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal Afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these Visceral sensory and motor neurons in vivo.
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presence and localization of neurotrophin receptor tyrosine kinase trka trkb trkc mrnas in Visceral Afferent neurons of the nodose and petrosal ganglia
Molecular Brain Research, 1996Co-Authors: Huang Zhou, Cinda J. HelkeAbstract:The presence of mRNAs to the high affinity tyrosine kinase (Trk) receptors for neurotrophins was studied in Visceral Afferent neurons of the nodose and petrosal ganglia of adult and neonatal rats using in situ hybridization histochemistry. Neurons containing TrkA mRNA were found in the adult nodose and petrosal ganglia. About 10% of nodose ganglion neurons and 38% of petrosal ganglion neurons contained TrkA mRNA. The nodose and petrosal ganglia from 1 day old neonates also expressed TrkA mRNA. No TrkB mRNA-containing neurons were detected in the adult nodose and petrosal ganglia, whereas TrkB mRNA was detected in 1 day old neonatal nodose and petrosal ganglia. TrkC mRNA was found in about 9% of nodose ganglion neurons and 11% of petrosal ganglion neurons of adult rats. Likewise, low but detectable levels of TrkC mRNA were seen in 1 day old neonatal nodose and petrosal ganglia. These data demonstrate the presence of TrkA and TrkC in the adult nodose and petrosal ganglia and provide a substrate for the ongoing neurotrophin-induced regulation of these placodally derived Visceral Afferent neurons. The altered expression of Trk receptor mRNAs in the nodose and petrosal ganglia between the adult and neonatal rats may reflect developmentally regulated changes in neurotrophin responsiveness.
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inhibition of axoplasmic transport in the rat vagus nerve alters the numbers of neuropeptide and tyrosine hydroxylase messenger rna containing and immunoreactive Visceral Afferent neurons of the nodose ganglion
Neuroscience, 1995Co-Authors: Huang Zhuo, A C Lewin, E T Phillips, C Sinclair, Cinda J. HelkeAbstract:Abstract Previous work showed that axotomy-induced deAfferentation of the placode-derived Visceral Afferent neurons of the nodose ganglion altered their expression of some neuropeptides and tyrosine hydroxylase. The present studies were designed to selectively evaluate the loss of axonal transport on the numbers of vasoactive intestinal polypeptide, tyrosine hydroxylase, and calcitonin gene-related peptide mRNA-containing and immunoreactive neurons in the nodose ganglion of the adult rat. Vinblastine (0.15 mM) application to the cervical vagus nerve was used to block axonal tranport between ganglionic perikarya and peripheral targets. In situ hybridization histochemistry with 35 S-labeled oligonucleotide probes was used to both quantify the number of mRNA-containing neurons and to assess the density of mRNA expression per neuron, and immunocytochemistryk was used to visualize the number of immunoreactive neurons. The efficacy of vinblastine to inhibit axonal transport was verified by evaluating the build-up of calcitonin gene-related peptide immunoreactive in the vagus nerve immediately rostral to the site of drug application. The absence of vinblastine-induced neuronal damage was verified by the relative absence of degenerating nerves in the vagus nerve caudal to the site of drug application. Vinblastine treatment of the vagus nerve increased the numbers of vasoactive intestinal peptide mRNA-containing neurons and vasoactive intestinal peptide-immunoreactive neurons in the nodose ganglion at three, seven and 14 days, and increased the numbers of calcitonin gene-related peptide mRNA-containing and calcitonin gene-related peptide-immunoreactive neurons in the nodose ganglion at one, three and seven days. The average labeling density of vasoactive intestinal peptide mRNA-containing neurons was also increased following vinblastine treatment. Vinblastine treatment of the cervical vagus nerve, however, led to the appearance of low-labeling density calcitonin gene-related peptide mRNA-neurons and resulted in reduction of the average labeling density for calcitonin gene-related peptide mRNA-containing neurons. In contrast, application of vinblastine to the cervical vagus nerve, decreased the number of tyrosine hydroxylase mRNA-containing and tyrosine hydroxylase-immunoreactive neurons in the nodose ganglion. In summary, inhibition of the axoplasmic transport between the periphery and the Visceral sensory perikarya appeared to alter vasoactive intestinal peptide, calcitonin gene-related peptide, and tyrosine hydroxylase expression and content in Visceral sensory neurons of the nodose ganglion. These data suggest the presence of an axonally transported influence on the regulation of neuropeptide and neurotransmitter enzyme synthesis in mature placode-derived Visceral sensory neurons.
Youngho Jin - One of the best experts on this subject based on the ideXlab platform.
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prostaglandin potentiates 5 ht responses in stomach and ileum innervating Visceral Afferent sensory neurons
Biochemical and Biophysical Research Communications, 2015Co-Authors: Sojin Kim, Zhenhua Jin, Goeun Lee, Yong Seek Park, Cheungseog Park, Youngho JinAbstract:Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on Visceral Afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in Visceral Afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.
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ginger and its pungent constituents non competitively inhibit serotonin currents on Visceral Afferent neurons
The Korean Journal of Physiology and Pharmacology, 2014Co-Authors: Zhenhua Jin, Sojin Kim, Goeun Lee, Yong Seek Park, Cheungseog Park, Youngho JinAbstract:Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate Visceral vagal Afferent nerve activity. Thus, 5-HT mediated vagal Afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed Visceral Afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal Afferent neurons.
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transient receptor potential trp a1 activated currents in trpv1 and cholecystokinin sensitive cranial Visceral Afferent neurons
Brain Research, 2011Co-Authors: Myungjin Choi, Zhenhua Jin, Yong Seek Park, Young Kyoung Rhee, Youngho JinAbstract:Abstract Culinary use of the pungent spices has potential health benefits including a reduction in food intake. Pungent spices often contain ingredients that activate members of the transient receptor potential (TRP) family A1 and evoke pain from capsaicin-sensitive somatosensory neurons. TRPA1 channel have also been identified on cranial Visceral Afferent neurons but their distribution and functional contributions are poorly understood. Visceral vagal neurons transduce mechanical and chemical signals from peripheral organs to the nucleus tractus solitarii. Many capsaicin-sensitive vagal Afferents participate in peripheral satiety signaling that includes cholecystokinin (CCK) sensitive neurons. To assess signaling, the TRPA1 selective agonist allyl isothiocyanate (AITC) was tested together with CCK and capsaicin (200 nM), a TRPV1 specific agonist. In isolated nodose neurons, AITC (0.05–0.2 mM) evoked concentration-dependent inward currents in 38% of the tested neurons. The TRPA1 specific antagonist HC-030031 (10 μM) blocked AITC responses. TRPA1 responses were mixed across neurons that were capsaicin-sensitive and -insensitive. However CCK evoked inward currents only on capsaicin-sensitive neurons and 28% of the CCK-sensitive neurons expressed TRPA1. Our results indicate that TRPA1 is co-expressed with TRPV1 in CCK-sensitive nodose neurons. The findings indicate a potential mechanism by which spices can act within cranial Visceral Afferent pathways mediating satiety and contribute to the reduction of the food intake associated with spiced diets.
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cellular heterogeneity within the solitary tract nucleus and Visceral Afferent processing electrophysiological approaches to discerning pathway performance
Tzu Chi Medical Journal, 2007Co-Authors: Michael C Andresen, James H Peters, Stuart J Mcdougall, Youngho Jin, Timothy W Bailey, Sue A AicherAbstract:Many homeostatic reflexes depend on autonomic central nervous system mechanisms to systemically coordinate Visceral organ function. The nucleus of the solitary tract (NTS) is the common entry of cranial Visceral Afferents into these regulatory pathways. Such NTS neurons initiate adjustments in cardiovascular, respiratory, gastrointestinal and other Visceral systems. Diversity of neurons within the NTS appears integral to such processing but is daunting to approach experimentally. This review outlines three experimental approaches to understanding cellular heterogeneity within NTS and its relation to function. Brainstem slice preparations coupled with patch recordings afford cellular-molecular resolution with substantial links to the more intact system. Pharmacological approaches based on Visceral Afferent phenotype have helped identify myelinated and unmyelinated solitary tract inputs to NTS neurons. An interesting outcome has been the robust association of A-type potassium currents with NTS neurons receiving unmyelinated Afferents. Neuroanatomical tracers offer a second, complementary approach. Anterograde transport of fluorescent dye identifies cranial Visceral Afferent terminals on second order neurons that cluster on or proximal to the soma-a highly unusual distribution in the central nervous system. Thus, second order baroreceptive neurons can be identified neuroanatomically in vitro. Equally helpful has been identification of NTS projection neurons by retrograde tracers injected into target regions of the hypothalamus or brainstem and this approach indicates substantial specialization-relative homogeneous neurons within the overall heterogeneity of NTS. Lastly, transgenic mouse strains, particularly those expressing marker chromophores, have identified phenotypic subtypes such as GABAergic inhibitory neurons within NTS. Combined methodologies are forging new understanding of NTS and autonomic regulation.
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vanilloid receptors presynaptically modulate cranial Visceral Afferent synaptic transmission in nucleus tractus solitarius
The Journal of Neuroscience, 2002Co-Authors: Mark W Doyle, Youngho Jin, Timothy W Bailey, Michael C AndresenAbstract:Although the central terminals of cranial Visceral Afferents express vanilloid receptor 1 (VR1), little is known about their functional properties at this first synapse within the nucleus tractus solitarius (NTS). Here, we examined whether VR1 modulates Afferent synaptic transmission. In horizontal brainstem slices, solitary tract (ST) activation evoked EPSCs. Monosynaptic EPSCs had low synaptic jitter (SD of latency to successive shocks) averaging 84.03 ± 3.74 μsec ( n = 72) and were completely blocked by the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[ f ]quinoxaline (NBQX). Sustained exposure to the VR1 agonist capsaicin (CAP; 100 nm) blocked ST EPSCs (CAP-sensitive) in some neurons but not others (CAP-resistant). CAP-sensitive EPSCs had longer latencies than CAP-resistant EPSCs (4.65 ± 0.27 msec, n = 48 vs 3.53 ± 0.28 msec, n = 24, respectively; p = 0.011), but they had similar jitter. CAP evoked two transient responses in CAP-sensitive neurons: a rapidly developing inward current ( I cap) (108.1 ± 22.9 pA; n = 21) and an increase in spontaneous synaptic activity. After 3–5 min in CAP, I cap subsided and ST EPSCs disappeared. NBQX completely blocked I cap. The VR1 antagonist capsazepine (10–20 μm) attenuated CAP responses. Anatomically, second-order NTS neurons were identified by 4-(4-dihexadecylamino)styryl)- N -methylpyridinium iodide transported from the cervical aortic depressor nerve (ADN) to stain central terminals. Neurons with fluorescent ADN contacts had CAP-sensitive EPSCs ( n = 5) with latencies and jitter similar to those of unlabeled monosynaptic neurons. Thus, consistent with presynaptic VR1 localization, CAP selectively activates a subset of ST axons to release glutamate that acts on non-NMDA receptors. Because the CAP sensitivity of cranial Afferents is exclusively associated with unmyelinated axons, VR1 identifies C-fiber Afferent pathways within the brainstem.
Michael C Andresen - One of the best experts on this subject based on the ideXlab platform.
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Cranial Visceral Afferent Pathways through the Nucleus of the Solitary Tract to Caudal Ventrolateral Medulla or Paraventricular Hypothalamus: Target-Specific Synaptic Reliability and Convergence Patterns
2013Co-Authors: Timothy W Bailey, Michael C Andresen, Sam M Hermes, Sue A AicherAbstract:Cranial Visceral Afferents activate central pathways that mediate systemic homeostatic processes. Afferent information arrives in the brainstem nucleus of the solitary tract (NTS) and is relayed to other CNS sites for integration into autonomic responses and complex behaviors. Little is known about the organization or nature of processing within NTS. We injected fluorescent retrograde tracers into two nuclei to identify neurons that project to sites involved in autonomic regulation: the caudal ventrolateral medulla (CVLM) or paraventricular nucleus of the hypothalamus (PVN). We found distinct differences in synaptic connections and performance in the Afferent path through NTS to these neurons. Anatomical studies using confocal and electron microscopy found prominent, primary Afferent synapses directly on somata and dendrites of CVLM-projecting NTS neurons identifying them as second-order neurons. In brainstem slices, Afferent activation evoked large, constant latency EPSCs in CVLM-projecting NTS neurons that were consistent with the precise timing and rare failures of monosynaptic contacts on second-order neurons. In contrast, most PVN-projecting NTS neurons lacked direct Afferent input and responded to Afferent stimuli with highly variable, intermittently failing synaptic responses, indicating polysynaptic pathways to higher-order neurons. The Afferent-evoked EPSCs in most PVN-projecting NTS neurons were smaller and unreliable but also often included multiple, convergent polysynaptic responses not observed in CVLM-projecting neurons. A few PVN-projecting NTS neurons had monosynaptic EPSC characteristics. Together, we found that cranial Visceral Afferent pathways are structured distinctly within NTS depending on the projection target. Such, intra-NTS pathway architecture will substantially impact performance of autonomi
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opioids inhibit Visceral Afferent activation of catecholamine neurons in the solitary tract nucleus
Neuroscience, 2012Co-Authors: Ran Ji Cui, Michael C Andresen, Brandon L Roberts, Huan Zhao, Suzanne M AppleyardAbstract:Brainstem A2/C2 catecholamine (CA) neurons within the solitary tract nucleus (NTS) influence many homeostatic functions, including food intake, stress, respiratory and cardiovascular reflexes. They also play a role in both opioid reward and withdrawal. Injections of opioids into the NTS modulate many autonomic functions influenced by catecholamine neurons including food intake and cardiac function. We recently showed that NTS-CA neurons are directly activated by incoming Visceral Afferent inputs. Here we determined whether opioid agonists modulate Afferent activation of NTS-CA neurons using transgenic mice with EGFP expressed under the control of the tyrosine hydroxylase promoter (TH-EGFP) to identify catecholamine neurons. The opioid agonist Met-enkephalin (Met-Enk) significantly attenuated solitary tract-evoked excitatory postsynaptic currents (ST-EPSCs) in NTS TH-EGFP neurons by 80%, an effect reversed by wash or the mu opioid receptor-specific antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP). Met-Enk had a significantly greater effect to inhibit Afferent inputs onto TH-EGFP-positive neurons than EGFP-negative neurons, which were only inhibited by 50%. The mu agonist, DAMGO, also inhibited the ST-EPSC in TH-EGFP neurons in a dose-dependent manner. In contrast, neither the delta agonist DPDPE, nor the kappa agonist, U69,593, consistently inhibited the ST-EPSC amplitude. Met-Enk and DAMGO increased the paired pulse ratio, decreased the frequency, but not amplitude, of mini-EPSCs and had no effect on holding current, input resistance or current-voltage relationships in TH-EGFP neurons, suggesting a presynaptic mechanism of action on Afferent terminals. Met-Enk significantly reduced both the basal firing rate of NTS TH-EGFP neurons and the ability of Afferent stimulation to evoke an action potential. These results suggest that opioids inhibit NTS-CA neurons by reducing an excitatory Afferent drive onto these neurons through presynaptic inhibition of glutamate release and elucidate one potential mechanism by which opioids could control autonomic functions and modulate reward and opioid withdrawal symptoms at the level of the NTS.
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cellular heterogeneity within the solitary tract nucleus and Visceral Afferent processing electrophysiological approaches to discerning pathway performance
Tzu Chi Medical Journal, 2007Co-Authors: Michael C Andresen, James H Peters, Stuart J Mcdougall, Youngho Jin, Timothy W Bailey, Sue A AicherAbstract:Many homeostatic reflexes depend on autonomic central nervous system mechanisms to systemically coordinate Visceral organ function. The nucleus of the solitary tract (NTS) is the common entry of cranial Visceral Afferents into these regulatory pathways. Such NTS neurons initiate adjustments in cardiovascular, respiratory, gastrointestinal and other Visceral systems. Diversity of neurons within the NTS appears integral to such processing but is daunting to approach experimentally. This review outlines three experimental approaches to understanding cellular heterogeneity within NTS and its relation to function. Brainstem slice preparations coupled with patch recordings afford cellular-molecular resolution with substantial links to the more intact system. Pharmacological approaches based on Visceral Afferent phenotype have helped identify myelinated and unmyelinated solitary tract inputs to NTS neurons. An interesting outcome has been the robust association of A-type potassium currents with NTS neurons receiving unmyelinated Afferents. Neuroanatomical tracers offer a second, complementary approach. Anterograde transport of fluorescent dye identifies cranial Visceral Afferent terminals on second order neurons that cluster on or proximal to the soma-a highly unusual distribution in the central nervous system. Thus, second order baroreceptive neurons can be identified neuroanatomically in vitro. Equally helpful has been identification of NTS projection neurons by retrograde tracers injected into target regions of the hypothalamus or brainstem and this approach indicates substantial specialization-relative homogeneous neurons within the overall heterogeneity of NTS. Lastly, transgenic mouse strains, particularly those expressing marker chromophores, have identified phenotypic subtypes such as GABAergic inhibitory neurons within NTS. Combined methodologies are forging new understanding of NTS and autonomic regulation.
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cranial Visceral Afferent pathways through the nucleus of the solitary tract to caudal ventrolateral medulla or paraventricular hypothalamus target specific synaptic reliability and convergence patterns
The Journal of Neuroscience, 2006Co-Authors: Timothy W Bailey, Michael C Andresen, Sam M Hermes, Sue A AicherAbstract:Cranial Visceral Afferents activate central pathways that mediate systemic homeostatic processes. Afferent information arrives in the brainstem nucleus of the solitary tract (NTS) and is relayed to other CNS sites for integration into autonomic responses and complex behaviors. Little is known about the organization or nature of processing within NTS. We injected fluorescent retrograde tracers into two nuclei to identify neurons that project to sites involved in autonomic regulation: the caudal ventrolateral medulla (CVLM) or paraventricular nucleus of the hypothalamus (PVN). We found distinct differences in synaptic connections and performance in the Afferent path through NTS to these neurons. Anatomical studies using confocal and electron microscopy found prominent, primary Afferent synapses directly on somata and dendrites of CVLM-projecting NTS neurons identifying them as second-order neurons. In brainstem slices, Afferent activation evoked large, constant latency EPSCs in CVLM-projecting NTS neurons that were consistent with the precise timing and rare failures of monosynaptic contacts on second-order neurons. In contrast, most PVN-projecting NTS neurons lacked direct Afferent input and responded to Afferent stimuli with highly variable, intermittently failing synaptic responses, indicating polysynaptic pathways to higher-order neurons. The Afferent-evoked EPSCs in most PVN-projecting NTS neurons were smaller and unreliable but also often included multiple, convergent polysynaptic responses not observed in CVLM-projecting neurons. A few PVN-projecting NTS neurons had monosynaptic EPSC characteristics. Together, we found that cranial Visceral Afferent pathways are structured distinctly within NTS depending on the projection target. Such, intra-NTS pathway architecture will substantially impact performance of autonomic or neuroendocrine reflex arcs.
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vanilloid receptors presynaptically modulate cranial Visceral Afferent synaptic transmission in nucleus tractus solitarius
The Journal of Neuroscience, 2002Co-Authors: Mark W Doyle, Youngho Jin, Timothy W Bailey, Michael C AndresenAbstract:Although the central terminals of cranial Visceral Afferents express vanilloid receptor 1 (VR1), little is known about their functional properties at this first synapse within the nucleus tractus solitarius (NTS). Here, we examined whether VR1 modulates Afferent synaptic transmission. In horizontal brainstem slices, solitary tract (ST) activation evoked EPSCs. Monosynaptic EPSCs had low synaptic jitter (SD of latency to successive shocks) averaging 84.03 ± 3.74 μsec ( n = 72) and were completely blocked by the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[ f ]quinoxaline (NBQX). Sustained exposure to the VR1 agonist capsaicin (CAP; 100 nm) blocked ST EPSCs (CAP-sensitive) in some neurons but not others (CAP-resistant). CAP-sensitive EPSCs had longer latencies than CAP-resistant EPSCs (4.65 ± 0.27 msec, n = 48 vs 3.53 ± 0.28 msec, n = 24, respectively; p = 0.011), but they had similar jitter. CAP evoked two transient responses in CAP-sensitive neurons: a rapidly developing inward current ( I cap) (108.1 ± 22.9 pA; n = 21) and an increase in spontaneous synaptic activity. After 3–5 min in CAP, I cap subsided and ST EPSCs disappeared. NBQX completely blocked I cap. The VR1 antagonist capsazepine (10–20 μm) attenuated CAP responses. Anatomically, second-order NTS neurons were identified by 4-(4-dihexadecylamino)styryl)- N -methylpyridinium iodide transported from the cervical aortic depressor nerve (ADN) to stain central terminals. Neurons with fluorescent ADN contacts had CAP-sensitive EPSCs ( n = 5) with latencies and jitter similar to those of unlabeled monosynaptic neurons. Thus, consistent with presynaptic VR1 localization, CAP selectively activates a subset of ST axons to release glutamate that acts on non-NMDA receptors. Because the CAP sensitivity of cranial Afferents is exclusively associated with unmyelinated axons, VR1 identifies C-fiber Afferent pathways within the brainstem.
Peter Holzer - One of the best experts on this subject based on the ideXlab platform.
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Visceral Afferent Neurons: Role in Gastric Mucosal Protection
2013Co-Authors: Peter Holzer, Maria Anna PabstAbstract:Gastric mucosal homeostasis requires rapid alarm of protective mechanisms in the face of pending injury. This article summarizes the evidence that spinal Afferent neurons monitor insults to the gastric mucosa and activate local mechanisms of defense and repair through release of transmitter peptides from their endings in the stomach. Nowhere else in the digestive system is the mucosa more endangered than in the gastroduodenal region, where it faces potential injury by noxious chemicals of endogenous and exogenous origin. Most tissues would rapidly disintegrate if exposed to the concentrations of HCl that bathe but do not harm the gastric surface epithelium. This is because a multitude of structural and physiological factors, collectively forming the gastric mucosal barrier, prevent hydrogen ions and other molecules from entering the tissue in quantities that produce cell damage. Although autonomic neurons have long been recognized to influence gastric mucosal defense against injury, the possibility that neurons constitute a rapid alarm system in the face of pending injury was hardly thought of. In particular, nociceptive Afferent neurons that innervate the stomach and whose role it is to monitor tissue damage and in turn activate mechanisms of protection have been little considered until recently. This neglect of sensory neurons is understandable, though, if judged against the multiple innervation of the gut by intrinsic enteric neurons and extrinsic autonomic and Afferent neurons, which has made a dissection of the specific roles played by Afferent neurons very difficult. Capsaicin as a probe for nociceptive neuron functions in the stomach The discovery that sensory neurons contribute to gastric mucosal homeostasis resulted from exploitation of a neuropharmacological trait that differentiates them from other neurons (3). Many primary Afferent neurons with C fibers and some with Aδ fibers are exclusively sensitive to th
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acid sensing by Visceral Afferent neurones
Acta Physiologica, 2011Co-Authors: Peter HolzerAbstract:Acidosis in the gastrointestinal tract can be both a physiological and pathological condition. While gastric acid serves digestion and protection from pathogens, pathological acidosis is associated with defective acid containment, inflammation and ischaemia. The pH in the oesophagus, stomach and intestine is surveyed by an elaborate network of acid-sensing mechanisms to maintain homeostasis. Deviations from physiological values of extracellular pH (7.4) are monitored by multiple acid sensors expressed by epithelial cells and sensory neurones. Protons evoke multiple currents in primary Afferent neurones, which are carried by several acid-sensitive ion channels. Among these, acid-sensing ion channels (ASICs) and transient receptor potential (TRP) vanilloid-1 (TRPV1) ion channels have been most thoroughly studied. ASICs survey moderate decreases in extracellular pH whereas TRPV1 is activated only by severe acidosis resulting in pH values below 6. Other molecular acid sensors comprise TRPV4, TRPC4, TRPC5, TRPP2 (PKD2L1), epithelial Na(+) channels, two-pore domain K(+) (K₂(P)) channels, ionotropic purinoceptors (P2X), inward rectifier K(+) channels, voltage-activated K(+) channels, L-type Ca²(+) channels and acid-sensitive G-protein-coupled receptors. Most of these acid sensors are expressed by primary sensory neurones, although to different degrees and in various combinations. As upregulation and overactivity of acid sensors appear to contribute to various forms of chronic inflammation and pain, acid-sensitive ion channels and receptors are also considered as targets for novel therapeutics.
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role of Visceral Afferent neurons in mucosal inflammation and defense
Current Opinion in Pharmacology, 2007Co-Authors: Peter HolzerAbstract:The maintenance of gastrointestinal (GI) mucosal integrity depends on the rapid alarm of protective mechanisms in the face of pending injury. Two populations of extrinsic primary Afferent neurons, vagal and spinal, subserve this goal through different mechanisms. These sensory neurons react to GI insults by triggering protective autonomic reflexes including the so-called cholinergic anti-inflammatory reflex. Spinal Afferents, in addition, can initiate protective tissue reactions at the site of assault through release of calcitonin gene-related peptide (CGRP) from their peripheral endings. The protective responses triggered by sensory neurons comprise alterations in GI blood flow, secretion, and motility as well as modifications of immune function. This article focusses on significant advances that during the past couple of years have been made in identifying molecular nocisensors on Afferent neurons and in dissecting the signaling mechanisms whereby Afferent neurons govern inflammatory processes in the gut.
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Visceral Afferent Neurons: Role in Gastric Mucosal Protection
Physiology, 1999Co-Authors: Peter Holzer, Maria Anna PabstAbstract:Gastric mucosal homeostasis requires rapid alarm of protective mechanisms in the face of pending injury. This article summarizes the evidence that spinal Afferent neurons monitor insults to the gastric mucosa and activate local mechanisms of defense and repair through release of transmitter peptides from their endings in the stomach.
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axonal transport of neurotrophins by Visceral Afferent and efferent neurons of the vagus nerve of the rat
The Journal of Comparative Neurology, 1998Co-Authors: Cinda J. Helke, K M Adryan, J Fedorowicz, H Zhuo, John S Park, Rory A J Curtis, H E Radley, Peter S DistefanoAbstract:The receptor-mediated axonal transport of [125I]-labeled neurotrophins by Afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal Afferent neurons retrogradely transported [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal Afferent neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor specificity of neurotrophin transport was examined by applying [125I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal Afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these Visceral sensory and motor neurons in vivo. J. Comp. Neurol. 393:102–117, 1998. Published 1998 Wiley-Liss, Inc.1
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Axonal transport of neurotrophins by Visceral Afferent and efferent neurons of the vagus nerve of the rat
The Journal of comparative neurology, 1998Co-Authors: Cinda J. Helke, K M Adryan, J Fedorowicz, H Zhuo, John S Park, Rory A J Curtis, H E Radley, Peter S DistefanoAbstract:The receptor-mediated axonal transport of [125I]-labeled neurotrophins by Afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal Afferent neurons retrogradely transported [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal Afferent neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor specificity of neurotrophin transport was examined by applying [125I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal Afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these Visceral sensory and motor neurons in vivo.
