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4.
Am J Physiol Regul Integr Comp Physiol ; 317(6): R879-R890, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618062

RESUMO

Although heart rate (HR) is governed by the sympathetic and parasympathetic nervous systems, a head-to-head comparison of the open-loop dynamic characteristics of the total arc from a baroreceptor pressure input to the HR response has yet to be performed. We estimated the transfer function from carotid sinus pressure input to the HR response (HCSP→HR) before and after bilateral vagotomy (n = 7) as well as before and after the administration of a ß-blocker propranolol (n = 8) in anesthetized male Wistar-Kyoto rats. The carotid sinus pressure was perturbed according to a Gaussian white noise signal so that the input power spectra were relatively flat between 0.01 and 1 Hz. The gain plot of HCSP→HR was V-shaped. Vagotomy reduced the dynamic gain at 1 Hz (0.0598 ± 0.0065 to 0.0025 ± 0.0004 beats·min-1·mmHg-1, P < 0.001) but not at 0.01 or 0.1 Hz. ß-Blockade reduced the dynamic gain at 0.01 Hz (0.247 ± 0.069 to 0.077 ± 0.017 beats·min-1·mmHg-1, P = 0.020) but not at 0.1 or 1 Hz. We also estimated the efferent limb transfer function from electrical vagal efferent stimulation to the HR response (HVN→HR) under ß-blockade conditions. We associated the model parameters of HVN→HR with the mean HR and the standard deviation of HR so that HVN→HR could be estimated based only on the HR data. We finally estimated the neural arc transfer function from a pressure input to efferent vagal nerve activity by dividing HCSP→HR by HVN→HR. The mathematically determined vagal neural arc showed derivative characteristics with its phase near zero radians at the lowest frequency.


Assuntos
Frequência Cardíaca/fisiologia , Sistema Nervoso Simpático/fisiologia , Nervo Vago/fisiologia , Animais , Barorreflexo , Pressão Sanguínea/fisiologia , Estimulação Elétrica , Masculino , Modelos Biológicos , Neurônios Eferentes , Propranolol , Ratos , Ratos Endogâmicos WKY
5.
Am J Physiol Gastrointest Liver Physiol ; 317(5): G694-G706, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31509431

RESUMO

The pancreas consists of both the exocrine (acini and ducts) and endocrine (islets) compartments to participate in and regulate the body's digestive and metabolic activities. These activities are subjected to neural modulation, but characterization of the human pancreatic afferent and efferent nerves remains difficult because of the lack of three-dimensional (3-D) image data. Here we prepare transparent human donor pancreases for 3-D histology to reveal the pancreatic microstructure, vasculature, and innervation in a global and integrated fashion. The pancreatic neural network consists of the substance P (SP)-positive sensory (afferent) nerves, the vesicular acetylcholine transporter (VAChT)-positive parasympathetic (efferent) nerves, and the tyrosine hydroxylase (TH)-positive sympathetic (efferent) nerves. The SP+ afferent nerves were found residing along the basal domain of the interlobular ducts. The VAChT+ and TH+ efferent nerves were identified at the peri-acinar and perivascular spaces, which follow the blood vessels to the islets. In the intrapancreatic ganglia, the SP+ (scattered minority, ~7%) and VAChT+ neurons co-localize, suggesting a local afferent-efferent interaction. Compared with the mouse pancreas, the human pancreas differs in 1) the lack of SP+ afferent nerves in the islet, 2) the lower ganglionic density, and 3) the obvious presence of VAChT+ and TH+ nerves around the intralobular adipocytes. The latter implicates the neural influence on the pancreatic steatosis. Overall, our 3-D image data reveal the human pancreatic afferent and efferent innervation patterns and provide the anatomical foundation for future high-definition analyses of neural remodeling in human pancreatic diseases.NEW & NOTEWORTHY Modern three-dimensional (3-D) histology with multiplex optical signals identifies the afferent and efferent innervation patterns of human pancreas, which otherwise cannot be defined with standard histology. Our 3-D image data reveal the unexpected association of sensory and parasympathetic nerves/neurons in the intrapancreatic ganglia and identify the sympathetic and parasympathetic nerve contacts with the infiltrated adipocytes. The multiplex approach offers a new way to characterize the human pancreas in remodeling (e.g., fatty infiltration and duct lesion progression).


Assuntos
Ilhotas Pancreáticas/citologia , Neurônios Aferentes/citologia , Neurônios Eferentes/citologia , Pâncreas Exócrino/citologia , Células Acinares/citologia , Tecido Adiposo/citologia , Tecido Adiposo/inervação , Adulto , Animais , Feminino , Humanos , Imageamento Tridimensional , Ilhotas Pancreáticas/inervação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Técnicas de Rastreamento Neuroanatômico , Neurônios Aferentes/metabolismo , Neurônios Eferentes/metabolismo , Pâncreas Exócrino/inervação , Substância P/genética , Substância P/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Proteínas Vesiculares de Transporte de Acetilcolina/genética , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo
6.
Elife ; 82019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31157617

RESUMO

In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial motor neurons (CrMN) are spared until late stages of the disease. Using a rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) to SpMNs and CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 and insoluble p62 than SpMNs over time. ESC-derived CrMNs have higher proteasome activity to degrade misfolded proteins and are intrinsically more resistant to chemically-induced proteostatic stress than SpMNs. Chemical and genetic activation of the proteasome rescues SpMN sensitivity to proteostatic stress. In agreement, the hSOD1 G93A mouse model reveals that ALS-resistant CrMNs accumulate less insoluble hSOD1 and p62-containing inclusions than SpMNs. Primary-derived ALS-resistant CrMNs are also more resistant than SpMNs to proteostatic stress. Thus, an ESC-based platform has identified a superior capacity to maintain a healthy proteome as a possible mechanism to resist ALS-induced neurodegeneration.


Assuntos
Esclerose Amiotrófica Lateral/genética , Glicoproteínas de Membrana/genética , Neurônios Motores/metabolismo , Neurônios Eferentes/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Superóxido Dismutase-1/genética , Esclerose Amiotrófica Lateral/patologia , Esclerose Amiotrófica Lateral/terapia , Animais , Diferenciação Celular/genética , Nervos Cranianos , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Transgênicos , Neurônios Motores/patologia , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Embrionárias Murinas/metabolismo , Neurônios Eferentes/efeitos dos fármacos , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/patologia
7.
Am J Physiol Regul Integr Comp Physiol ; 317(2): R337-R345, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31116019

RESUMO

Systemic anaphylaxis is a life-threatening and allergic reaction that affects various organs. We previously reported that, in the stomach, gastric vasoconstriction occurring at the late phase (15-55 min after injection of ovalbumin antigen) was observed in anesthetized rats sensitized with ovalbumin. In addition, anaphylaxis enhances gastric motility and delays emptying. However, the role of extrinsic autonomic nervous system on antigen-induced gastric alterations was not known. Thus, using the same rat anaphylaxis model, we aimed to determine the changes in the efferent and afferent autonomic nerve activities in the stomach during anaphylactic hypotension. The findings showed that injection of ovalbumin antigen caused substantial systemic hypotension in all sensitized rats. The efferent gastric sympathetic nerve activity (ef-GSNA), but not the efferent vagal nerve activity, increased only at the early phase (1-10 min after injection of ovalbumin antigen) and showed baroreceptor reflex, as evidenced by a stimulatory response to sodium nitroprusside-induced hypotension. In general, excitation of ef-GSNA could induce pylorus sphincter contraction and gastric vasoconstriction. In the present study, we found that sympathectomy attenuated the anaphylaxis-induced decrease in gastric flux but not the increase in gastric vascular resistance. Thus, the increase in ef-GSNA may cause anaphylactic pylorus sphincter contraction but not anaphylactic gastric vasoconstriction. On the other hand, the afferent gastric vagal nerve activity, but not the afferent sympathetic nerve activity, increased during the early phase of anaphylactic hypotension. However, vagotomy produced no effects on the anaphylactic gastric dysfunction. In conclusion, the gastric sympathetic nerves partly modulate stomach function during systemic anaphylaxis.


Assuntos
Anafilaxia/fisiopatologia , Estômago/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Nervo Vago/fisiopatologia , Anafilaxia/induzido quimicamente , Animais , Barorreflexo , Hipotensão/fisiopatologia , Masculino , Neurônios Eferentes , Nitroprussiato/farmacologia , Ratos Sprague-Dawley , Estômago/inervação , Nervo Vago/fisiologia , Resistência Vascular/fisiologia
8.
PLoS One ; 14(4): e0215036, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970000

RESUMO

OBJECTIVE: We aimed to refine electroneurogram techniques for monitoring hypogastric nerve activity during bladder filling, and then examined nerve activity in normal intact versus acutely decentralized bladders. METHODS: Effects of electrical stimulation of hypogastric nerves or lumbar ventral roots on detrusor pressure were examined, as were effects of isoflurane versus propofol anesthetics on hypogastric nerve stimulation evoked pressure. Hypogastric nerve activity was then recorded using custom-made bipolar cuff electrodes during bladder filling before and after its transection between the spinal cord and electrode to eliminate efferent nerve signals. RESULTS: Electrical stimulation of hypogastric nerves evoked low amplitude detrusor pressures that did not differ between the two anesthetics. Upper lumbar (L2) ventral root stimulation evoked detrusor pressures were suppressed, yet not eliminated, after transection of hypogastric nerves and all spinal roots below L5. Afferent and efferent hypogastric nerve activity did not change with bladder filling in neuronally intact bladders yet decreased in decentralized bladders. No change in afferent activity was observed during bladder filling in either intact or decentralized bladders. CONCLUSIONS: These findings indicate that a more complete decentralized bladder model should include transection of lumbosacral spinal roots innervating the bladder as well as hypogastric nerves. These refined electroneurogram recording methods may be suitable for evaluating the effectiveness of nerve transfer surgeries for bladder reinnervation by monitoring sensory activity in the transferred nerve.


Assuntos
Estimulação Elétrica , Raízes Nervosas Espinhais/fisiologia , Sistema Nervoso Simpático/fisiologia , Bexiga Urinária/fisiologia , Animais , Cães , Potenciais Evocados , Isoflurano/farmacologia , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Neurônios Eferentes/efeitos dos fármacos , Neurônios Eferentes/fisiologia , Propofol/farmacologia , Raízes Nervosas Espinhais/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos
9.
PLoS One ; 14(3): e0213088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30835756

RESUMO

Dopamine release in the nucleus accumbens from ventral tegmental area (VTA) efferent neurons is critical for orientation and response to novel stimuli in the environment. However, there are considerable differences between neuronal populations of the VTA and it is unclear which specific cell populations modulate behavioral responses to environmental novelty. A retroDREADDs (designer drugs exclusively activated by designer receptors) technique, comprising designer G protein-coupled receptors exclusively activated by designer drugs and modulated by retrograde transported Cre, was used to selectively stimulate neurons of the VTA which project to the nucleus accumbens shell (AcbSh). First, the selectivity and expression of the human M3 muscarinic receptor-based adeno-associated virus (AAV-hM3D) was confirmed in primary neuronal cell cultures. Second, AAV-CMV-GFP/Cre was infused into the AcbSh and AAV-hSyn-DIO-hM3D(Gq)-mCherry (a presynaptic enhancer in the presence of its cognate ligand clozapine-N-oxide) was infused into the VTA of ovariectomized female Fisher 344 rats to elicit hM3D(Gq)-mCherry production specifically in neurons of the VTA which synapse in the AcbSh. Finally, administration of clozapine-N-oxide significantly altered rodents' response to novelty (e.g. absence of white background noise) by activation of hM3D(Gq) receptors, without altering gross locomotor activity or auditory processing per se. Confocal imaging confirmed production of mCherry in neurons of the posterior aspect of the VTA (pVTA) suggesting these neurons contribute to novelty responses. These results suggest the pVTA-AcbSh circuit is potentially altered in motivational disorders such as apathy, depression, and drug addiction. Targeting the pVTA-AcbSh circuit, therefore, may be an effective target for pharmacological management of such psychopathologies.


Assuntos
Comportamento Exploratório , Neurônios Eferentes/citologia , Núcleo Accumbens/fisiologia , Receptor Muscarínico M3/metabolismo , Área Tegmentar Ventral/fisiologia , Animais , Células Cultivadas , Clozapina/análogos & derivados , Clozapina/farmacologia , Drogas Desenhadas/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Feminino , Humanos , Locomoção/efeitos dos fármacos , Neurônios Eferentes/efeitos dos fármacos , Neurônios Eferentes/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Ovariectomia , Ratos , Sinapses/fisiologia , Área Tegmentar Ventral/efeitos dos fármacos
11.
Elife ; 82019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30714901

RESUMO

For animals to perform coordinated movements requires the precise organization of neural circuits controlling motor function. Motor neurons (MNs), key components of these circuits, project their axons from the central nervous system and form precise terminal branching patterns at specific muscles. Focusing on the Drosophila leg neuromuscular system, we show that the stereotyped terminal branching of a subset of MNs is mediated by interacting transmembrane Ig superfamily proteins DIP-α and Dpr10, present in MNs and target muscles, respectively. The DIP-α/Dpr10 interaction is needed only after MN axons reach the vicinity of their muscle targets. Live imaging suggests that precise terminal branching patterns are gradually established by DIP-α/Dpr10-dependent interactions between fine axon filopodia and developing muscles. Further, different leg MNs depend on the DIP-α and Dpr10 interaction to varying degrees that correlate with the morphological complexity of the MNs and their muscle targets.


Assuntos
Proteínas de Drosophila/genética , Neurônios Motores/fisiologia , Neurogênese/genética , Fatores de Transcrição/genética , Animais , Axônios/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Neurônios Motores/metabolismo , Neurônios Eferentes/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Fatores de Transcrição/metabolismo
12.
Mol Neurobiol ; 56(2): 797-811, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29797183

RESUMO

While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A1-dopamine D1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D1 receptor-mediated signaling. A1-D1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.


Assuntos
Cafeína/farmacologia , Neurônios Motores/efeitos dos fármacos , Receptores de Dopamina D1/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Adenosina/farmacologia , Células Cultivadas , Dopamina/farmacologia , Humanos , Neurônios Eferentes/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos
13.
J Vis ; 18(13): 9, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30550620

RESUMO

To estimate object speed with respect to the self, retinal signals must be summed with extraretinal signals that encode the speed of eye and head movement. Prior work has shown that differences in perceptual estimates of object speed based on retinal and oculomotor signals lead to biased percepts such as the Aubert-Fleischl phenomenon (AF), in which moving targets appear slower when pursued. During whole-body movement, additional extraretinal signals, such as those from the vestibular system, may be used to transform object speed estimates from a head-centered to a world-centered reference frame. Here we demonstrate that whole-body pursuit in the form of passive yaw rotation, which stimulates the semicircular canals of the vestibular system, leads to a slowing of perceived object speed similar to the classic oculomotor AF. We find that the magnitude of the vestibular and oculomotor AF is comparable across a range of speeds, despite the different types of input signal involved. This covariation might hint at a common modality-independent mechanism underlying the AF in both cases.


Assuntos
Movimentos Oculares/fisiologia , Percepção de Movimento/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino , Neurônios Aferentes/fisiologia , Neurônios Eferentes/fisiologia , Adulto Jovem
14.
Curr Med Sci ; 38(6): 982-988, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30536059

RESUMO

The precise anatomy of the facial nerve branches innervating rat whisker pad and the distribution of their corresponding motor neurons in facial nucleus area were investigated. The extratemporal facial nerves of 6 rats were anatomically observed under a surgical microscope, and then the nerve specimens of facial nerve branches at 7 anatomical sites were taken and examined for the axons and myelin sheath using Luxol fast blue staining. The distribution of facial motor neurons innervating the facial branches was observed in 12 rats by retrograde labelling. The distal pes, a fusing architecture of the buccal and marginal mandibular branches, was found to furcate into superior, middle and inferior branches to innervate whisker pad. Histologically, the myelin sheath of each branch was morphologically consistent, and the nerve fiber bundles of facial nerve branches became increasingly thinner and scattered, particularly after crossing the distal pes site and innervating the whisker pad. The facial motor neurons innervating the buccal and marginal mandibular branches were clearly distributed in similar regions in facial nucleus. This study confirmed the highly spatial synergy between the buccal and marginal mandibular branches innervating the whisker pad from extratemporal anatomy and distribution of facial motor neurons.


Assuntos
Face/inervação , Nervo Facial/anatomia & histologia , Núcleo do Nervo Facial/anatomia & histologia , Vibrissas/inervação , Animais , Masculino , Neurônios Motores/fisiologia , Fenômenos Fisiológicos Musculoesqueléticos , Bainha de Mielina/fisiologia , Neurônios Eferentes/fisiologia , Ratos , Ratos Sprague-Dawley , Vibrissas/fisiologia
15.
Am J Physiol Regul Integr Comp Physiol ; 315(6): R1261-R1271, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30332305

RESUMO

Recent evidence suggests hypertension may be secondary to chronic inflammation that results from hypoactive neuro-immune regulatory mechanisms. To further understand this association, we used systemic lupus erythematosus (SLE) as a model of inflammation-induced hypertension. In addition to prevalent inflammatory kidney disease and hypertension, SLE patients suffer from dysautonomia in the form of decreased efferent vagal tone. Based on this, the cholinergic anti-inflammatory pathway, an endogenous vagus-to-spleen mechanism that, when activated results in decreases in systemic inflammation, may be compromised in SLE. We hypothesized that stimulation of the cholinergic anti-inflammatory pathway via pharmacological potentiation of the efferent vagus nerve would reduce inflammation and halt the development of hypertension and renal injury in SLE. Female NZBWF1 mice, an established model of murine SLE, and female control mice were treated with galantamine (4 mg/kg daily ip), an acetylcholinesterase inhibitor, or saline for 14 days. At the end of therapy, carotid catheters were surgically implanted and were used to measure mean arterial pressure before the animals were euthanized. Chronic galantamine administration attenuated both splenic and renal cortical inflammation, which likely explains why the hypertension and renal injury (i.e., glomerulosclerosis and fibrosis) typically observed in murine SLE was attenuated following therapy. Based on this, the anti-inflammatory, antihypertensive, and renoprotective effects of galantamine may be mediated through activation of the cholinergic anti-inflammatory pathway. It is possible that dysfunction of the cholinergic anti-inflammatory pathway exists in SLE at the level of the efferent vagus nerve and promoting restoration of its activity through central cholinergic receptor activation may be beneficial.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Galantamina/farmacologia , Hipertensão/tratamento farmacológico , Nervo Vago/efeitos dos fármacos , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos Transgênicos , Neurônios Eferentes/efeitos dos fármacos , Nervo Vago/fisiopatologia
16.
Curr Opin Neurobiol ; 53: 156-161, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30205323

RESUMO

Proprioceptive sensory input and descending supraspinal projections are two major inputs that feed into and influence spinal circuitry and locomotor behaviors. Here we review their influence on each other during development and after spinal cord injury. We highlight developmental mechanisms of circuit formation as they relate to the sensory-motor circuit and its reciprocal interactions with local spinal interneurons, as well as competitive interactions between proprioceptive and descending supraspinal inputs in the setting of spinal cord injury.


Assuntos
Interneurônios/fisiologia , Locomoção/fisiologia , Rede Nervosa/fisiologia , Neurônios Aferentes/fisiologia , Neurônios Eferentes/fisiologia , Propriocepção/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiologia , Animais , Humanos , Rede Nervosa/crescimento & desenvolvimento , Medula Espinal/crescimento & desenvolvimento
17.
Neuroreport ; 29(15): 1315-1322, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30169427

RESUMO

The vestibular center of the brainstem contains afferent and efferent vestibular neurons, which play an important role in information perception, processing, and sensory integration. Vestibular efferent neurons (VENs) can receive changes in vestibular afferent information and regulate peripheral vestibular function; however, it remains unclear how VENs change after vestibular afferent information increases or weakens. In this study, we used animal models with altered vestibular afferent information by electrically stimulating or destroying the vestibular medial nucleus (MVe). We confirmed the location of VENs in the brainstem by injecting five adult male Wistar rats in the vestibular region with a retrograde tracer. Following this, the MVe was stimulated electrically for 30 min in 20 naive rats. Rats were anesthetized and euthanized 1, 3, 6, and 12 h after stimulation. The MVe was electrolytically lesioned in another group (n=20); then, the rats were anesthetized and euthanized 1, 3, 5, and 7 days after lesioning. VENs were clearly identified dorsolateral to the genu of the facial nerve (g7) in coronal brainstem sections using choline acetyltransferase (ChAT) staining. The number of ChAT-positive VENs dorsolateral to g7 increased significantly on both sides compared with the control group 3 and 6 h after electrical stimulation. The number of ChAT-positive VENs dorsolateral to g7 was significantly greater on both sides compared with controls 3 and 5 days after electrolytic lesion. In summary, we found that the number of ChAT-positive VENs was significantly increased following a change in the excitability of MVe neurons. This suggests that VENs can respond to changes in afferent vestibular information and feedback, and regulate the peripheral vestibule. In addition, this shows that acetylcholine is an important neurotransmitter that plays an important role in the perception and fine regulation of the vestibular system.


Assuntos
Colina O-Acetiltransferase/metabolismo , Neurônios Eferentes/citologia , Neurônios Eferentes/metabolismo , Núcleos Vestibulares/citologia , Núcleos Vestibulares/metabolismo , Animais , Estimulação Elétrica , Imunofluorescência , Masculino , Potenciais da Membrana , Técnicas de Rastreamento Neuroanatômico , Neurônios Eferentes/patologia , Ratos Wistar , Núcleos Vestibulares/patologia
18.
Sci Rep ; 8(1): 11990, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-30097601

RESUMO

Peripheral nerve injury impairs motor and sensory function in humans, and its functional recovery largely depends on the axonal outgrowth required for the accurate reinnervation of appropriate targets. To better understand how motor and sensory nerve fibres select their terminal pathways, an unbiased cDNA microarray analysis was conducted to examine differential gene expression patterns in peripheral efferent and afferent fibres at different developmental stages in mice. Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analyses revealed common and distinct features of enrichment for differentially expressed genes during motor and sensory nerve fibre development. Ingenuity Pathway Analysis (IPA) further indicated that the key differentially expressed genes were associated with trans-synaptic neurexin-neuroligin signalling components and a variety of gamma-aminobutyric acid (GABA) receptors. The aim of this study was to generate a framework of gene networks regulated during motor and sensory neuron differentiation/maturation. These data may provide new clues regarding the underlying cellular and molecular mechanisms that determine the intrinsic capacity of neurons to regenerate after peripheral nerve injury. Our findings may thus facilitate further development of a potential intervention to manipulate the therapeutic efficiency of peripheral nerve repair in the clinic.


Assuntos
Perfilação da Expressão Gênica , Fibras Nervosas/metabolismo , Neurogênese/genética , Neurônios Aferentes/metabolismo , Neurônios Eferentes/metabolismo , Nervos Periféricos/metabolismo , Transcriptoma , Animais , Análise por Conglomerados , Biologia Computacional/métodos , Regulação da Expressão Gênica , Ontologia Genética , Camundongos , Neurônios Motores/metabolismo , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/patologia , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais
19.
Elife ; 72018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30113308

RESUMO

The neuromuscular junction (NMJ) is a synapse between motoneurons and skeletal muscles to control motor behavior. Unlike extensively investigated postsynaptic differentiation, less is known about mechanisms of presynaptic assembly. Genetic evidence of Wnt in mammalian NMJ development was missing due to the existence of multiple Wnts and their receptors. We show when Wnt secretion is abolished from motoneurons by mutating the Wnt ligand secretion mediator (Wls) gene, mutant mice showed muscle weakness and neurotransmission impairment. NMJs were unstable with reduced synaptic junctional folds and fragmented AChR clusters. Nerve terminals were swollen; synaptic vesicles were fewer and mislocated. The presynaptic deficits occurred earlier than postsynaptic deficits. Intriguingly, these phenotypes were not observed when deleting Wls in muscles or Schwann cells. We identified Wnt7A and Wnt7B as major Wnts for nerve terminal development in rescue experiments. These observations demonstrate a necessary role of motoneuron Wnts in NMJ development, in particular presynaptic differentiation.


Assuntos
Neurônios Motores/metabolismo , Junção Neuromuscular/crescimento & desenvolvimento , Proteínas Proto-Oncogênicas/genética , Proteínas Wnt/genética , Animais , Diferenciação Celular/genética , Camundongos , Neurônios Motores/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Mutação , Junção Neuromuscular/genética , Neurônios Eferentes/metabolismo , Receptores Colinérgicos/genética , Células de Schwann/citologia , Células de Schwann/metabolismo , Sinapses/genética , Via de Sinalização Wnt
20.
PLoS One ; 13(8): e0202822, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30142206

RESUMO

The stick insect is a well-established experimental animal to study the neural basis of walking. Here, we introduce a preparation that allows combining calcium imaging in efferent neurons with electrophysiological recordings of motor neuron activity in the stick insect thoracic nerve cord. The intracellular free calcium concentration in middle leg retractor coxae motor neurons and modulatory octopaminergic DUM neurons was monitored after backfilling lateral nerve nl5 that contains the axons of these neurons with the calcium indicator Oregon Green BAPTA-1. Rhythmic spike activity in retractor and protractor motor neurons was evoked by pharmacological activation of central pattern generating neuronal networks and recorded extracellularly from lateral nerves. A primary goal of this study was to investigate whether changes in the intracellular free calcium concentration observed in motor neurons during oscillatory activity depend on action potentials. We show that rhythmic spike activity in leg motor neurons induced either pharmacologically or by tactile stimulation of the animal is accompanied by a synchronous modulation in the intracellular free calcium concentration. Calcium oscillations in motor neurons do not appear to depend on calcium influx through voltage-sensitive calcium channels that are gated by action potentials because Calcium oscillations persist after pharmacologically blocking action potentials in the motor neurons. Calcium oscillations were also apparent in the modulatory DUM neurons innervating the same leg muscle. However, the timing of calcium oscillations varied not only between DUM neurons and motor neurons, but also among different DUM neurons. Therefore, we conclude that the motor neurons and the different DUM neurons receive independent central drive.


Assuntos
Cálcio/metabolismo , Neurônios Eferentes/fisiologia , Animais , Potenciais Evocados/efeitos dos fármacos , Feminino , Insetos/fisiologia , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , Neurônios Eferentes/efeitos dos fármacos , Neurônios Eferentes/enzimologia , Pilocarpina/farmacologia
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