Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23.949
Filtrar
1.
Toxicol Lett ; 331: 33-41, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32445661

RESUMO

This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20∼postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.


Assuntos
Dexametasona/toxicidade , Ácido Glutâmico/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ácido gama-Aminobutírico/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Animais Recém-Nascidos , Arginina Vasopressina/metabolismo , Corticosterona/sangue , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/metabolismo , Glutamato Descarboxilase/metabolismo , Sistema Hipotálamo-Hipofisário/embriologia , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Neurônios Aferentes/metabolismo , Núcleo Hipotalâmico Paraventricular/embriologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/embriologia , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos
2.
Nat Commun ; 11(1): 1739, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269213

RESUMO

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.


Assuntos
Neurônios Colinérgicos/fisiologia , Mesencéfalo/fisiologia , Neostriado/fisiologia , Rede Nervosa/fisiologia , Neurônios Aferentes/fisiologia , Animais , Comportamento Animal , Feminino , Objetivos , Interneurônios/fisiologia , Masculino , Camundongos , Optogenética , Fosforilação , Ratos Long-Evans , Sinapses/fisiologia
3.
J Oral Sci ; 62(2): 147-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224567

RESUMO

Pain can be divided into nociceptive, inflammatory, and neuropathic pain. It is important to understanding the molecular mechanism of pain signaling in the development of pain relief therapies. Twenty years ago, extracellular signal-regulated kinases (ERK) 1 and 2, which are members of the mitogen-activated protein kinase superfamily, were identified as molecules activated in neurons by the exposure of peripheral tissues to noxious stimuli. Further studies have revealed that peripheral nerve injury induces ERK activation in glial cells, sensory neurons, and second-order neurons, albeit at different time points. Moreover, inhibition of ERK suppresses pathological pain in animals with peripheral nerve injury. Therefore, ERK is currently recognized as an important molecule in pain signaling and a potential novel target for pain treatment. This review introduces recent advances in revealing the regulation of ERK in pain research.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , Neuralgia , Animais , Neuroglia , Neurônios Aferentes
4.
Neuron ; 106(5): 816-829.e6, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32229307

RESUMO

Sodium taste regulates salt intake. The amiloride-sensitive epithelial sodium channel (ENaC) is the Na+ sensor in taste cells mediating attraction to sodium salts. However, cells and intracellular signaling underlying sodium taste in taste buds remain long-standing enigmas. Here, we show that a subset of taste cells with ENaC activity fire action potentials in response to ENaC-mediated Na+ influx without changing the intracellular Ca2+ concentration and form a channel synapse with afferent neurons involving the voltage-gated neurotransmitter-release channel composed of calcium homeostasis modulator 1 (CALHM1) and CALHM3 (CALHM1/3). Genetic elimination of ENaC in CALHM1-expressing cells as well as global CALHM3 deletion abolished amiloride-sensitive neural responses and attenuated behavioral attraction to NaCl. Together, sodium taste is mediated by cells expressing ENaC and CALHM1/3, where oral Na+ entry elicits suprathreshold depolarization for action potentials driving voltage-dependent neurotransmission via the channel synapse. Thus, all steps in sodium taste signaling are voltage driven and independent of Ca2+ signals. This work also reveals ENaC-independent salt attraction.


Assuntos
Potenciais de Ação/fisiologia , Cálcio/metabolismo , Canais Epiteliais de Sódio/metabolismo , Sódio/metabolismo , Papilas Gustativas/citologia , Paladar/fisiologia , Potenciais de Ação/efeitos dos fármacos , Amilorida/farmacologia , Animais , Canais de Cálcio/metabolismo , Células Quimiorreceptoras/metabolismo , Células Quimiorreceptoras/fisiologia , Bloqueadores do Canal de Sódio Epitelial/farmacologia , Camundongos , Neurônios Aferentes/metabolismo , Técnicas de Patch-Clamp , Transdução de Sinais/efeitos dos fármacos , Transmissão Sináptica , Papilas Gustativas/metabolismo , Papilas Gustativas/fisiologia
5.
J Vis Exp ; (156)2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32116290

RESUMO

Tooth innervation allows teeth to sense pressure, temperature and inflammation, all of which are crucial to the use and maintenance of the tooth organ. Without sensory innervation, daily oral activities would cause irreparable damage. Despite its importance, the roles of innervation in tooth development and maintenance have been largely overlooked. Several studies have demonstrated that DP cells secrete extracellular matrix proteins and paracrine signals to attract and guide TG axons into and throughout the tooth. However, few studies have provided detailed insight into the crosstalk between the DP mesenchyme and neuronal afferents. To address this gap in knowledge, researchers have begun to utilize co-cultures and a variety of techniques to investigate these interactions. Here, we demonstrate the multiple steps involved in co-culturing primary DP cells with TG neurons dispersed on an overlying transwell filter with large diameter pores to allow axonal growth through the pores. Primary DP cells with the gene of interest flanked by loxP sites were utilized to facilitate gene deletion using an Adenovirus-Cre-GFP recombinase system. Using TG neurons from the Thy1-YFP mouse allowed for precise afferent imaging, with expression well above background levels by confocal microscopy. The DP responses can be investigated via protein or RNA collection and analysis, or alternatively, through immunofluorescent staining of DP cells plated on removable glass coverslips. Media can be analyzed using techniques such as proteomic analyses, although this will require albumin depletion due to the presence of fetal bovine serum in the media. This protocol provides a simple method that can be manipulated to study the morphological, genetic, and cytoskeletal responses of TG neurons and DP cells in response to the controlled environment of a co-culture assay.


Assuntos
Técnicas de Cocultura/métodos , Polpa Dentária/metabolismo , Crescimento Neuronal , Comunicação Parácrina , Animais , Dissecação , Imageamento Tridimensional , Mesoderma , Camundongos , Neurônios Aferentes/fisiologia
6.
Neuron ; 106(4): 624-636.e4, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-32191871

RESUMO

The ventral tegmental area (VTA) is a major target of addictive drugs and receives multiple GABAergic projections originating outside the VTA. We describe differences in synaptic plasticity and behavior when optogenetically driving two opiate-sensitive GABAergic inputs to the VTA, the rostromedial tegmental nucleus (RMTg), and the periaqueductal gray (PAG). Activation of GABAergic RMTg terminals in the VTA in vivo is aversive, and low-frequency stimulation induces long-term depression in vitro. Low-frequency stimulation of PAG afferents in vitro unexpectedly causes long-term potentiation. Opioid receptor activation profoundly depresses PAG and RMTg inhibitory synapses but prevents synaptic plasticity only at PAG synapses. Activation of the GABAergic PAG terminals in the VTA promotes immobility, and optogenetically-driven immobility is blocked by morphine. Our data reveal the PAG as a source of highly opioid-sensitive GABAergic afferents and support the idea that different GABAergic pathways to the VTA control distinct behaviors.


Assuntos
Analgésicos Opioides/farmacologia , Plasticidade Neuronal/fisiologia , Neurônios Aferentes/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Feminino , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Tegmento Mesencefálico , Área Tegmentar Ventral/efeitos dos fármacos
7.
Am J Physiol Cell Physiol ; 318(4): C787-C796, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32073876

RESUMO

Cholecystokinin (CCK) is a gut-derived peptide that potently promotes satiety and facilitates gastric function in part by activating G protein-coupled CCK1 receptors on primary vagal afferent neurons. CCK signaling is dynamic and rapidly desensitizes, due to decreases in either receptor function and the resulting signal cascade, ion channel effectors, or both. Here we report a decay-time analytical approach using fluorescent calcium imaging that relates peak and steady-state calcium responses in dissociated vagal afferent neurons, enabling discrimination between receptor and ion channel effector functions. We found desensitization of CCK-induced activation was predictable, consistent across cells, and strongly concentration dependent. The decay-time constant (tau) was inversely proportional to CCK concentration, apparently reflecting the extent of receptor activation. To test this possibility, we directly manipulated the ion channel effector(s) with either decreased bath calcium or the broad-spectrum pore blocker ruthenium red. Conductance inhibition diminished the magnitude of the CCK responses without altering decay kinetics, confirming changes in tau reflect changes in receptor function selectively. Next, we investigated the contributions of the PKC and PKA signaling cascades on the magnitude and decay-time constants of CCK calcium responses. While inhibition of either PKC or PKA increased CCK calcium response magnitude, only general PKC inhibition significantly decreased the decay-time constant. These findings suggest that PKC alters CCK receptor signaling dynamics, while PKA alters the ion channel effector of the CCK response. This analytical approach should prove useful in understanding receptor/effector changes underlying acute desensitization of G-protein coupled signaling and provide insight into CCK receptor dynamics.


Assuntos
Colecistocinina/farmacologia , Neurônios Aferentes/efeitos dos fármacos , Gânglio Nodoso/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Animais , Cálcio/metabolismo , Neurônios/efeitos dos fármacos , Neurônios Aferentes/citologia , Neurônios Aferentes/fisiologia , Gânglio Nodoso/citologia , Gânglio Nodoso/fisiologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
10.
Proc Natl Acad Sci U S A ; 117(1): 698-707, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31848242

RESUMO

Group III/IV muscle afferents transduce nociceptive signals and modulate exercise pressor reflexes (EPRs). However, the mechanisms governing afferent responsiveness to dually modulate these processes are not well characterized. We and others have shown that ischemic injury can induce both nociception-related behaviors and exacerbated EPRs in the same mice. This correlated with primary muscle afferent sensitization and increased expression of glial cell line-derived neurotrophic factor (GDNF) in injured muscle and increased expression of GDNF family receptor α1 (GFRα1) in dorsal root ganglia (DRG). Here, we report that increased GDNF/GFRα1 signaling to sensory neurons from ischemia/reperfusion-affected muscle directly modulated nociceptive-like behaviors and increased exercise-mediated reflexes and group III/IV muscle afferent sensitization. This appeared to have taken effect through increased cyclic adenosine monophosphate (cAMP) response element binding (CREB)/CREB binding protein-mediated expression of the purinergic receptor P2X5 in the DRGs. Muscle GDNF signaling to neurons may, therefore, play an important dual role in nociception and sympathetic reflexes and could provide a therapeutic target for treating complications from ischemic injuries.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Mialgia/etiologia , Nociceptividade/fisiologia , Reflexo/fisiologia , Traumatismo por Reperfusão/patologia , Animais , Proteína de Ligação a CREB/metabolismo , Sistema Cardiovascular/inervação , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Exercício Físico/fisiologia , Gânglios Espinais/metabolismo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Frequência Cardíaca/fisiologia , Humanos , Masculino , Camundongos , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Mialgia/patologia , Neurônios Aferentes/fisiologia , Receptores Purinérgicos P2X5/metabolismo , Traumatismo por Reperfusão/complicações , Transdução de Sinais/fisiologia
11.
J Pharmacol Exp Ther ; 372(1): 73-82, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31771994

RESUMO

Itch stimuli are detected by specialized primary afferents that convey the signal to the spinal cord, but how itch transmission is regulated is still not completely known. Here, we investigated the roles of the neuropeptide Y (NPY)/Y2 receptor system on scratch behavior. The inhibitory Y2 receptor is expressed on mouse primary afferents, and intrathecal administration of the Y2 agonist peptide YY (PYY)3-36 reduced scratch episode frequency and duration induced by compound 48/80, an effect that could be reversed by intrathecal preadministration of the Y2 antagonist BIIE0246. Also, scratch episode duration induced by histamine could be reduced by PYY3-36 In contrast, scratch behavior induced by α-methyl-5HT, protease-activated receptor-2-activating peptide SLIGRL, chloroquine, topical dust mite extract, or mechanical itch induced by von Frey filaments was unaffected by stimulation of Y2 Primary afferent neurons expressing the Npy2r gene were found to coexpress itch-associated markers such as natriuretic peptide precursor b, oncostatin M receptor, and interleukin (IL) 31 receptor A. Accordingly, intrathecal PYY3-36 reduced the scratch behavior induced by IL-31. Our findings imply that the NPY/Y2 system reduces histaminergic and IL-31-associated itch through presynaptic inhibition of a subpopulation of itch-associated primary afferents. SIGNIFICANCE STATEMENT: The spinal neuropeptide Y system dampens scratching behavior induced by histaminergic compounds and interleukin 31, a cytokine involved in atopic dermatitis, through interactions with the Y2 receptor. The Y2 receptor is expressed by primary afferent neurons that are rich in itch-associated neurotransmitters and receptors such as somatostatin, natriuretic peptide precursor b, and interleukin 31 receptors.


Assuntos
Antipruriginosos/farmacologia , Dermatite Atópica/metabolismo , Neurônios Aferentes/metabolismo , Fragmentos de Peptídeos/farmacologia , Peptídeo YY/farmacologia , Prurido/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Animais , Antipruriginosos/administração & dosagem , Antipruriginosos/uso terapêutico , Arginina/análogos & derivados , Arginina/toxicidade , Benzazepinas/toxicidade , Células Cultivadas , Cloroquina/farmacologia , Dermatite Atópica/tratamento farmacológico , Gânglios Espinais/citologia , Histamina/farmacologia , Histamina/toxicidade , Interleucinas/farmacologia , Interleucinas/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/uso terapêutico , Peptídeo YY/administração & dosagem , Peptídeo YY/uso terapêutico , Prurido/tratamento farmacológico , Prurido/etiologia , Receptores de Neuropeptídeo Y/genética , Receptores de Oncostatina M/genética , Receptores de Oncostatina M/metabolismo , Serotonina/farmacologia
12.
Exp Neurol ; 323: 113092, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31697943

RESUMO

Dramatic impairment of gastrointestinal (GI) function accompanies high-thoracic spinal cord injury (T3-SCI). The vagus nerve contains mechano- and chemosensory fibers as well as the motor fibers necessary for the central nervous system (CNS) control of GI reflexes. Cell bodies for the vagal afferent fibers are located within the nodose gangla (NG) and the majority of vagal afferent axons are unmyelinated C fibers that are sensitive to capsaicin through activation of transient receptor potential vanilloid-1 (TRPV1) channels. Vagal afferent fibers also express receptors for GI hormones, including cholecystokinin (CCK). Previously, T3-SCI provokes a transient GI inflammatory response as well as a reduction of both gastric emptying and centrally-mediated vagal responses to GI peptides, including CCK. TRPV1 channels and CCK-A receptors (CCKar) expressed in vagal afferents are upregulated in models of visceral inflammation. The present study investigated whether T3-SCI attenuates peripheral vagal afferent sensitivity through plasticity of TRPV1 and CCK receptors. Vagal afferent response to graded mechanical stimulation of the stomach was significantly attenuated by T3-SCI at 3-day and 3-week recovery. Immunocytochemical labeling for CCKar and TRPV1 demonstrated expression on dissociated gastric-projecting NG neurons. Quantitative assessment of mRNA expression by qRT-PCR revealed significant elevation of CCKar and TRPV1 in the whole NG following T3-SCI in 3-day recovery, but levels returned to normal after 3-weeks. Three days after injury, systemic administration of CCK-8 s showed a significantly diminished gastric vagal afferent response in T3-SCI rats compared to control rats while systemic capsaicin infusion revealed a significant elevation of vagal response in T3-SCI vs control rats. These findings demonstrate that T3-SCI provokes peripheral remodeling and prolonged alterations in the response of vagal afferent fibers to the physiological signals associated with digestion.


Assuntos
Neurônios Aferentes/metabolismo , Receptores da Colecistocinina/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Canais de Cátion TRPV/metabolismo , Nervo Vago/fisiopatologia , Animais , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Masculino , Plasticidade Neuronal/fisiologia , Ratos , Ratos Wistar , Traumatismos da Medula Espinal/complicações , Estômago/inervação , Vértebras Torácicas , Nervo Vago/metabolismo
13.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31824648

RESUMO

The transient receptor potential vanilloid 1 (TRPV1) is densely expressed in spinal sensory neurons as well as in cranial sensory neurons, including their central terminal endings. Recent work in the less familiar cranial sensory neurons, despite their many similarities with spinal sensory neurons, suggest that TRPV1 acts as a calcium channel to release a discrete population of synaptic vesicles. The modular and independent regulation of release offers new questions about nanodomain organization of release and selective actions of G protein-coupled receptors.


Assuntos
Transdução de Sinais , Animais , Potenciais Pós-Sinápticos Excitadores , Neurônios Aferentes , Núcleo Solitário , Canais de Cátion TRPV
14.
Acta Neurobiol Exp (Wars) ; 79(4): 432-444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885399

RESUMO

Previous studies have shown that Roux­en­Y gastric bypass (RYGB), one of the most effective weight loss treatments for obesity, results in neurodegenerative responses in vagal afferent gut­brain connection reflected by microglia activation and reduced sensory input to the nucleus tractus solitarius (NTS). However, it is not known whether RYGB­induced microglia activation is the cause or an effect of the reported neuronal damage. Therefore, the aim of this study was to establish the order of neurodegenerative responses in vagal afferents after RYGB in the nodose ganglia (NG) and NTS in male and female rats. Sprague­Dawley rats were fed regular chow or an energy­dense diet for two weeks followed by RYGB or sham surgery. Twenty­four hours later, animals were sacrificed and NG and NTS were collected. Neuronal cell damage was determined by TUNEL assay. Microglia activation was determined by quantifying the fluorescent staining against the ionizing calcium adapter­binding molecule 1. Reorganization of vagal afferents was evaluated by fluorescent staining against isolectin 4. Results of the study revealed significantly increased DNA fragmentation in vagal neurons in the NG when observed at 24 h after RYGB. The surgery did not produce rapid changes in the density of vagal afferents and microglia activation in the NTS. These data indicate that decreased density of vagal afferents and increased microglia activation in the NTS likely ensue as a res ult of RYGB­induced neuronal damage.


Assuntos
Fragmentação do DNA , Ingestão de Energia , Comportamento Alimentar , Derivação Gástrica/efeitos adversos , Complicações Intraoperatórias/metabolismo , Microglia/metabolismo , Neurônios Aferentes/metabolismo , Gânglio Nodoso/metabolismo , Núcleo Solitário/metabolismo , Traumatismos do Nervo Vago/metabolismo , Nervo Vago/metabolismo , Vias Aferentes/fisiopatologia , Animais , Composição Corporal , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Feminino , Complicações Intraoperatórias/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismos do Nervo Vago/etiologia
15.
Nihon Yakurigaku Zasshi ; 154(5): 255-258, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735754

RESUMO

Bladder afferent nerves are composed by myelinated Aδ- and unmyelinated C-fibers. During the storage phase of urine, distention of the bladder has long been considered to evoke afferent activity via Aδ-fibers connected in series with the smooth muscle fibers. In contrast, a previous study in cats revealed that more than 90% of C-fibers do not respond to normal bladder distension, being so called 〝silent〟 fibers. However, at least in rats, C-fibers can respond to normal bladder distension like Aδ-fibers, although they may also fulfill a potentially different role in the bladder sensory function in response to abnormal stimuli. The symptoms of overactive bladder (OAB) or interstitial cystitis (IC) are believed to be commonly related to the sensory (afferent) function. In addition, it has been suggested that bladder myogenic microcontractions or micromotions may partly contribute to the development of urgency in OAB related to bladder outlet obstruction (BOO), which is one of cause of benign prostatic hyperplasia (BPH). We have investigated the direct effects of drugs (anticholinergics, ß3-adrenoceptor agonists, α1-adrenoceptor antagonists, PDE type5 inhibitors, etc.) on the bladder afferent function in rodents. In our results, almost all drugs may act on the bladder afferent function, and some of drug (e.g. mirabegron) inhibits the afferent activities through the suppression of the bladder myogenic microcontractions in normal or pathophysiological conditions.


Assuntos
Vias Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Bexiga Urinária Hiperativa/fisiopatologia , Bexiga Urinária/inervação , Animais , Gatos , Fibras Nervosas Amielínicas , Ratos , Sensação
16.
Neuron ; 104(5): 987-999.e4, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31627985

RESUMO

Persistence of reward seeking despite punishment or other negative consequences is a defining feature of mania and addiction, and numerous brain regions have been implicated in such punishment learning, but in disparate ways that are difficult to reconcile. We now show that the ability of an aversive punisher to inhibit reward seeking depends on coordinated activity of three distinct afferents to the rostromedial tegmental nucleus (RMTg) arising from cortex, brainstem, and habenula that drive triply dissociable RMTg responses to aversive cues, outcomes, and prediction errors, respectively. These three pathways drive correspondingly dissociable aspects of punishment learning. The RMTg in turn drives negative, but not positive, valence encoding patterns in the ventral tegmental area (VTA). Hence, punishment learning involves pathways and functions that are highly distinct, yet tightly coordinated.


Assuntos
Aprendizagem/fisiologia , Vias Neurais/fisiologia , Punição , Recompensa , Tegmento Mesencefálico/fisiologia , Animais , Masculino , Neurônios Aferentes/fisiologia , Ratos , Ratos Sprague-Dawley , Área Tegmentar Ventral/fisiologia
17.
Elife ; 82019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570121

RESUMO

It has been known for more than a century that, in adult vertebrates, the maintenance of taste buds depends on their afferent nerves. However, the initial formation of taste buds is proposed to be nerve-independent in amphibians, and evidence to the contrary in mammals has been endlessly debated, mostly due to indirect and incomplete means to impede innervation during the protracted perinatal period of taste bud differentiation. Here, by genetically ablating, in mice, all somatic (i.e. touch) or visceral (i.e. taste) neurons for the oral cavity, we show that the latter but not the former are absolutely required for the proper formation of their target organs, the taste buds.


Assuntos
Boca/inervação , Neurônios Aferentes/fisiologia , Organogênese , Papilas Gustativas/crescimento & desenvolvimento , Animais , Camundongos
18.
Neuron ; 104(5): 960-971.e7, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31630908

RESUMO

Rapid conduction of nerve impulses is critical in life and relies on action potential (AP) leaps through the nodes of Ranvier (NRs) along myelinated nerves. While NRs are the only sites where APs can be regenerated during nerve conduction on myelinated nerves, ion channel mechanisms underlying the regeneration and conduction of APs at mammalian NRs remain incompletely understood. Here, we show that TREK-1 and TRAAK, the thermosensitive and mechanosensitive two-pore-domain potassium (K2P) channels, are clustered at NRs of rat trigeminal Aß-afferent nerves with a density over 3,000-fold higher than that on their somas. These K2P channels, but not voltage-gated K+ channels as in other parts of nerves, are required for rapid AP repolarization at the NRs. Furthermore, these channels permit high-speed and high-frequency AP conduction along the myelinated afferent nerves, and loss of function of these channels at NRs retards nerve conduction and impairs sensory behavioral responses in animals.


Assuntos
Potenciais de Ação/fisiologia , Condução Nervosa/fisiologia , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Canais de Potássio/metabolismo , Nós Neurofibrosos/metabolismo , Animais , Masculino , Fibras Nervosas Mielinizadas/metabolismo , Neurônios Aferentes/metabolismo , Ratos , Ratos Sprague-Dawley
19.
Dev Cogn Neurosci ; 39: 100703, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31487608

RESUMO

Preterm birth is a significant risk factor for a range of long-term health problems and developmental disabilities. Though touch plays a central role in many perinatal care strategies, the neurobiological basis of these approaches is seldom considered. C-Tactile afferents (CTs) are a class of unmyelinated nerve fibre activated by low force, dynamic touch. Consistent with an interoceptive function, touch specifically targeted to activate CTs activates posterior insular cortex and has been reported to reduce autonomic arousal. The present study compared the effect of 5 min of CT optimal velocity stroking touch to 5 min of static touch on the heart-rate and oxygen saturation levels of preterm infants between 28- & 37-weeks gestational age. CT touch produced a significant decrease in infants' heart-rates and increase in their blood oxygenation levels, which sustained throughout a 5-min post-touch period. In contrast, there was no significant change in heart-rate or blood oxygenation levels of infants receiving static touch. These findings provide support for the hypothesis that CTs signal the affective quality of nurturing touch, providing a neurobiological substrate for the apparent beneficial effects of neonatal tactile interventions and offering insight for their optimisation.


Assuntos
Nível de Alerta/fisiologia , Recém-Nascido Prematuro/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Neurônios Aferentes/fisiologia , Percepção do Tato/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Masculino , Distribuição Aleatória , Tato/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA