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1.
PLoS One ; 16(12): e0261060, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972120

RESUMO

Affective touch refers to the emotional and motivational facets of tactile sensation and has been linked to the activation of a specialised system of mechanosensory afferents (the CT system), that respond optimally to slow caress-like touch. Affective touch has been shown to play an important role in the building of the bodily self: the multisensory integrated global awareness of one's own body. Here we investigated the effects of affective touch on subsequent tactile awareness and multisensory integration using the Somatic Signal Detection Task (SSDT). During the SSDT, participants were required to detect near-threshold tactile stimulation on their cheek, in the presence/absence of a concomitant light. Participants repeated the SSDT twice, before and after receiving a touch manipulation. Participants were divided into two groups: one received affective touch (CT optimal; n = 32), and the second received non-affective touch (non-CT optimal; n = 34). Levels of arousal (skin conductance levels, SCLs) and mood changes after the touch manipulation were also measured. Affective touch led to an increase in tactile accuracy, as indicated by less false reports of touch and a trend towards higher tactile sensitivity during the subsequent SSDT. Conversely, non-affective touch was found to induce a partial decrease in the correct detection of touch possibly due to a desensitization of skin mechanoreceptors. Both affective and non-affective touch induced a more positive mood and higher SCLs in participants. The increase in SCLs was greater after affective touch. We conclude that receiving affective touch enhances the sense of bodily self therefore increasing perceptual accuracy and awareness. Higher SCLs are suggested to be a possible mediator linking affective touch to a greater tactile accuracy. Clinical implications are discussed.


Assuntos
Afeto/fisiologia , Fenômenos Fisiológicos da Pele , Análise e Desempenho de Tarefas , Percepção do Tato/fisiologia , Tato/fisiologia , Adulto , Vias Aferentes/fisiologia , Nível de Alerta , Feminino , Resposta Galvânica da Pele , Humanos , Pessoa de Meia-Idade , Autorrelato , Inquéritos e Questionários , Adulto Jovem
2.
PLoS One ; 16(12): e0260663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34905543

RESUMO

Short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) occur when the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) is reduced by the delivery of a preceding peripheral nerve stimulus. The intra-individual variability in SAI and LAI is considerable, and the influence of sample demographics (e.g., age and biological sex) and testing context (e.g., time of day) is not clear. There are also no established normative values for these measures, and their reliability varies from study-to-study. To address these issues and facilitate the interpretation of SAI and LAI research, we pooled data from studies published by our lab between 2014 and 2020 and performed several retrospective analyses. Patterns in the depth of inhibition with respect to age, biological sex and time of testing were investigated, and the relative reliability of measurements from studies with repeated baseline SAI and LAI assessments was examined. Normative SAI and LAI values with respect to the mean and standard deviation were also calculated. Our data show no relationship between the depth of inhibition for SAI and LAI with either time of day or age. Further, there was no significant difference in SAI or LAI between males and females. Intra-class correlation coefficients (ICC) for repeated measurements of SAI and LAI ranged from moderate (ICC = 0.526) to strong (ICC = 0.881). The mean value of SAI was 0.71 ± 0.27 and the mean value of LAI was 0.61 ± 0.34. This retrospective study provides normative values, reliability estimates, and an exploration of demographic and testing influences on these measures as assessed in our lab. To further facilitate the interpretation of SAI and LAI data, similar studies should be performed by other labs that use these measures.


Assuntos
Vias Aferentes/fisiologia , Potencial Evocado Motor/fisiologia , Nervo Mediano/fisiologia , Córtex Motor/fisiologia , Inibição Neural/fisiologia , Adulto , Fatores Etários , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/anatomia & histologia , Tempo de Reação/fisiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores Sexuais , Estimulação Magnética Transcraniana
3.
Nat Commun ; 12(1): 3730, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140480

RESUMO

Acid taste, evoked mainly by protons (H+), is a core taste modality for many organisms. The hedonic valence of acid taste is bidirectional: animals prefer slightly but avoid highly acidic foods. However, how animals discriminate low from high acidity remains poorly understood. To explore the taste perception of acid, we use the fruit fly as a model organism. We find that flies employ two competing taste sensory pathways to detect low and high acidity, and the relative degree of activation of each determines either attractive or aversive responses. Moreover, we establish one member of the fly Otopetrin family, Otopetrin-like a (OtopLa), as a proton channel dedicated to the gustatory detection of acid. OtopLa defines a unique subset of gustatory receptor neurons and is selectively required for attractive rather than aversive taste responses. Loss of otopla causes flies to reject normally attractive low-acid foods. Therefore, the identification of OtopLa as a low-acid sensor firmly supports our competition model of acid taste sensation. Altogether, we have discovered a binary acid-sensing mechanism that may be evolutionarily conserved between insects and mammals.


Assuntos
Ácidos/metabolismo , Vias Aferentes/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Neurônios/metabolismo , Vias Aferentes/fisiologia , Animais , Animais Geneticamente Modificados , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Eletrofisiologia , Células HEK293 , Humanos , Concentração de Íons de Hidrogênio , Imuno-Histoquímica , Malatos/metabolismo , Microscopia Confocal , Mutação , Neurônios/fisiologia , Receptores de Superfície Celular/metabolismo , Proteínas Recombinantes , Paladar/fisiologia , Percepção Gustatória/fisiologia
4.
Clin Neurophysiol ; 132(7): 1462-1480, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030051

RESUMO

Transcranial magnetic stimulation (TMS) paired with nerve stimulation evokes short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI), which are non-invasive assessments of the excitability of the sensorimotor system. SAI and LAI are abnormally reduced in various special populations in comparison to healthy controls. However, the relationship between afferent inhibition and human behavior remains unclear. The purpose of this review is to survey the current literature and synthesize observations and patterns that affect the interpretation of SAI and LAI in the context of human behavior. We discuss human behaviour across the motor and cognitive domains, and in special and control populations. Further, we discuss future considerations for research in this field and the potential for clinical applications. By understanding how human behavior is mediated by changes in SAI and LAI, this can allow us to better understand the neurophysiological underpinnings of human motor control.


Assuntos
Comportamento/fisiologia , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Estimulação Magnética Transcraniana/métodos , Vias Aferentes/fisiologia , Humanos
5.
Nutrients ; 13(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807524

RESUMO

Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is under circadian control and fluctuates depending on the time of day. These rhythms are highly correlated with meal size, with a nadir in VA sensitivity and increase in meal size during the dark phase and a peak in sensitivity and decrease in meal size during the light phase in mice. These rhythms are disrupted in diet-induced obesity and simulated shift work conditions and associated with disrupted food intake patterns. In diet-induced obesity the dampened responses during the light phase are not simply reversed by reverting back to a normal diet. However, time restricted feeding prevents loss of diurnal rhythms in VA signalling in high fat diet-fed mice and, therefore, provides a potential strategy to reset diurnal rhythms in VA signalling to a pre-obese phenotype. This review discusses the role of the circadian system in the regulation of gastrointestinal VA signals and the impact of factors, such as diet-induced obesity and shift work, on these rhythms.


Assuntos
Vias Aferentes/fisiologia , Regulação do Apetite/fisiologia , Ritmo Circadiano/fisiologia , Trato Gastrointestinal/inervação , Nervo Vago/fisiologia , Animais , Dieta Hiperlipídica/efeitos adversos , Jejum/fisiologia , Humanos , Camundongos , Obesidade/fisiopatologia
6.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800863

RESUMO

The ability to sense and move within an environment are complex functions necessary for the survival of nearly all species. The spinal cord is both the initial entry site for peripheral information and the final output site for motor response, placing spinal circuits as paramount in mediating sensory responses and coordinating movement. This is partly accomplished through the activation of complex spinal microcircuits that gate afferent signals to filter extraneous stimuli from various sensory modalities and determine which signals are transmitted to higher order structures in the CNS and to spinal motor pathways. A mechanistic understanding of how inhibitory interneurons are organized and employed within the spinal cord will provide potential access points for therapeutics targeting inhibitory deficits underlying various pathologies including sensory and movement disorders. Recent studies using transgenic manipulations, neurochemical profiling, and single-cell transcriptomics have identified distinct populations of inhibitory interneurons which express an array of genetic and/or neurochemical markers that constitute functional microcircuits. In this review, we provide an overview of identified neural components that make up inhibitory microcircuits within the dorsal and ventral spinal cord and highlight the importance of inhibitory control of sensorimotor pathways at the spinal level.


Assuntos
Vias Aferentes/fisiologia , Interneurônios/fisiologia , Movimento/fisiologia , Inibição Neural/fisiologia , Sensação/fisiologia , Filtro Sensorial/fisiologia , Medula Espinal/citologia , Animais , Células do Corno Anterior/química , Células do Corno Anterior/classificação , Células do Corno Anterior/fisiologia , Humanos , Interneurônios/química , Interneurônios/classificação , Modelos Neurológicos , Neurônios Motores/fisiologia , Transtornos dos Movimentos/fisiopatologia , Fibras Nervosas/fisiologia , Proteínas do Tecido Nervoso/análise , Neuropeptídeos/análise , Células do Corno Posterior/química , Células do Corno Posterior/classificação , Transtornos das Sensações/fisiopatologia , Células Receptoras Sensoriais/fisiologia , Medula Espinal/fisiologia , Sinapses/fisiologia
7.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33688051

RESUMO

For neuronal circuits in the brain to mature, necessary synapses must be maintained and redundant synapses eliminated through experience-dependent mechanisms. However, the functional differentiation of these synapse types during the refinement process remains elusive. Here, we addressed this issue by distinct labeling and direct recordings of presynaptic terminals fated for survival and for elimination in the somatosensory thalamus. At surviving terminals, the number of total releasable vesicles was first enlarged, and then calcium channels and fast-releasing synaptic vesicles were tightly coupled in an experience-dependent manner. By contrast, transmitter release mechanisms did not mature at terminals fated for elimination, irrespective of sensory experience. Nonetheless, terminals fated for survival and for elimination both exhibited developmental shortening of action potential waveforms that was experience independent. Thus, we dissected experience-dependent and -independent developmental maturation processes of surviving and eliminated presynaptic terminals during neuronal circuit refinement.


Assuntos
Terminações Pré-Sinápticas/fisiologia , Potenciais de Ação , Vias Aferentes/fisiologia , Animais , Canais de Cálcio/metabolismo , Camundongos , Rede Nervosa/fisiologia , Neurotransmissores/metabolismo , Vesículas Sinápticas/metabolismo , Núcleos do Trigêmeo/fisiologia , Núcleos Ventrais do Tálamo/fisiologia , Vibrissas/inervação , Vibrissas/fisiologia
8.
J Neurophysiol ; 125(4): 1517-1531, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33689491

RESUMO

The rat whisker system connects the tactile environment with the somatosensory thalamocortical system using only two synaptic stages. Encoding properties of the first stage, the primary afferents with somas in the trigeminal ganglion (TG), has been well studied, whereas much less is known from the second stage, the brainstem trigeminal nuclei (TN). The TN are a computational hub giving rise to parallel ascending tactile pathways and receiving feedback from many brain sites. We asked the question, whether encoding properties of TG neurons are kept by two trigeminal nuclei, the principalis (Pr5) and the spinalis interpolaris (Sp5i), respectively giving rise to two "lemniscal" and two "nonlemniscal" pathways. Single units were recorded in anesthetized rats while a single whisker was deflected on a band-limited white noise trajectory. Using information theoretic methods and spike-triggered mixture models (STM), we found that both nuclei encode the stimulus locally in time, i.e., stimulus features more than 10 ms in the past do not significantly influence spike generation. They further encode stimulus kinematics in multiple, distinct response fields, indicating encoding characteristics beyond previously described directional responses. Compared with TG, Pr5 and Sp5i gave rise to lower spike and information rates, but information rate per spike was on par with TG. Importantly, both brainstem nuclei were found to largely keep encoding properties of primary afferents, i.e. local encoding and kinematic response fields. The preservation of encoding properties in channels assumed to serve different functions seems surprising. We discuss the possibility that it might reflect specific constraints of frictional whisker contact with object surfaces.NEW & NOTEWORTHY We studied two trigeminal nuclei containing the second neuron on the tactile pathway of whisker-related tactile information in rats. We found that the subnuclei, traditionally assumed to give rise to functional tactile channels, nevertheless transfer primary afferent information with quite similar properties in terms of integration time and kinematic profile. We discuss whether such commonality may be due the requirement to adapt to physical constraints of frictional whisker contact.


Assuntos
Fenômenos Eletrofisiológicos/fisiologia , Neurônios Aferentes/fisiologia , Percepção do Tato/fisiologia , Núcleos do Trigêmeo/fisiologia , Vibrissas/fisiologia , Vias Aferentes/fisiologia , Animais , Fenômenos Biomecânicos , Ratos , Fatores de Tempo
9.
Neurosci Lett ; 748: 135719, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33587987

RESUMO

Transient Receptor Potential (TRP) channels expressed in specific subsets of airway sensory nerves function as transducers and integrators of a diverse range of sensory inputs including chemical, mechanical and thermal signals. These TRP sensors can detect inhaled irritants as well as endogenously released chemical substances. They play an important role in generating the afferent activity carried by these sensory nerves and regulating the centrally mediated pulmonary defense reflexes. Increasing evidence reported in recent investigations has revealed important involvements of several TRP channels (TRPA1, TRPV1, TRPV4 and TRPM8) in the manifestation of various symptoms and pathogenesis of certain acute and chronic airway diseases. This mini-review focuses primarily on these recent findings of the responses of these TRP sensors to the biological stresses emerging under the pathophysiological conditions of the lung and airways.


Assuntos
Vias Aferentes/fisiologia , Pulmão/fisiologia , Células Receptoras Sensoriais/fisiologia , Canais de Potencial de Receptor Transitório/fisiologia , Animais , Humanos , Pulmão/inervação , Sistema Nervoso Periférico , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
10.
Annu Rev Physiol ; 83: 429-450, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33566672

RESUMO

Renal sympathetic (efferent) nerves play an important role in the regulation of renal function, including glomerular filtration, sodium reabsorption, and renin release. The kidney is also innervated by sensory (afferent) nerves that relay information to the brain to modulate sympathetic outflow. Hypertension and other cardiometabolic diseases are linked to overactivity of renal sympathetic and sensory nerves, but our mechanistic understanding of these relationships is limited. Clinical trials of catheter-based renal nerve ablation to treat hypertension have yielded promising results. Therefore, a greater understanding of how renal nerves control the kidney under physiological and pathophysiological conditions is needed. In this review, we provide an overview of the current knowledge of the anatomy of efferent and afferent renal nerves and their functions in normal and pathophysiological conditions. We also suggest further avenues of research for development of novel therapies targeting the renal nerves.


Assuntos
Vias Aferentes/fisiologia , Hipertensão/fisiopatologia , Rim/inervação , Rim/fisiologia , Animais , Ablação por Cateter/métodos , Humanos , Rim/fisiopatologia
11.
Mol Pain ; 17: 1744806921992620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33586515

RESUMO

BACKGROUND: Spinal GABAergic neurons act as a critical modulator in sensory transmission like pain or itch. The monosynaptic or polysynaptic primary afferent inputs onto GABAergic neurons, along with other interneurons or projection neurons make up the direct and feed-forward inhibitory neural circuits. Previous research indicates that spinal GABAergic neurons mainly receive excitatory inputs from Aδ and C fibers. However, whether they are controlled by other inhibitory sending signals is not well understood. METHODS: We applied a transgenic mouse line in which neurons co-expressed the GABA-synthesizing enzyme Gad65 and the enhanced red fluorescence (td-Tomato) to characterize the features of morphology and electrophysiology of GABAergic neurons. Patch-clamp whole cell recordings were used to record the evoked postsynaptic potentials of fluorescent neurons in spinal slices in response to dorsal root stimulation. RESULTS: We demonstrated that GABAergic neurons not only received excitatory drive from peripheral Aß, Aδ and C fibers, but also received inhibitory inputs driven by Aδ and C fibers. The evoked inhibitory postsynaptic potentials (eIPSPs) mediated by C fibers were mainly Glycinergic (66.7%) as well as GABAergic mixed with Glycinergic (33.3%), whereas the inhibition mediated by Aδ fibers was predominately both GABA and Glycine-dominant (57.1%), and the rest of which was purely Glycine-dominant (42.9%). CONCLUSION: These results indicated that spinal GABAergic inhibitory neurons are under feedforward inhibitory control driven by primary C and Aδ fibers, suggesting that this feed-forward inhibitory pathway may play an important role in balancing the excitability of GABAergic neurons in spinal dorsal horn.


Assuntos
Neurônios GABAérgicos/fisiologia , Glutamato Descarboxilase/metabolismo , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Inibição Neural/fisiologia , Medula Espinal/fisiologia , Potenciais de Ação/fisiologia , Vias Aferentes/fisiologia , Animais , Glicina/metabolismo , Interneurônios/fisiologia , Camundongos Transgênicos , Ácido gama-Aminobutírico/metabolismo
12.
Neurosci Lett ; 744: 135604, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-33387662

RESUMO

Airway afferents monitor the local chemical and physical micro-environments in the airway wall and lungs and send this information centrally to regulate neural circuits involved in setting autonomic tone, evoking reflex and volitional respiratory motor outflows, encoding perceivable sensations and contributing to higher order cognitive processing. In this mini-review we present a current overview of the central wiring of airway afferent circuits in the brainstem and brain, highlighting recent discoveries that augment our understanding of airway sensory processing. We additionally explore how advances in describing the molecular diversity of airway afferents may influence future research efforts aimed at defining central mesoscale connectivity of airway afferent pathways. A refined understanding of how functionally distinct airway afferent pathways are organized in the brain will provide deeper insight into the physiology of airway afferent-evoked responses and may foster opportunities for targeted modulation of specific pathways involved in disease.


Assuntos
Vias Aferentes/fisiologia , Tronco Encefálico/fisiologia , Rede Nervosa/fisiologia , Fenômenos Fisiológicos Respiratórios , Sistema Respiratório/inervação , Nervo Vago/fisiologia , Vias Aferentes/diagnóstico por imagem , Animais , Tronco Encefálico/diagnóstico por imagem , Humanos , Rede Nervosa/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Sistema Respiratório/diagnóstico por imagem , Núcleo Solitário/diagnóstico por imagem , Núcleo Solitário/fisiologia , Nervo Vago/diagnóstico por imagem
13.
Am J Physiol Gastrointest Liver Physiol ; 320(2): G183-G192, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33206550

RESUMO

Gastric vagal afferents (GVAs) sense food-related mechanical stimuli and signal to the central nervous system, to integrate control of meal termination. Pregnancy is characterized by increased maternal food intake, which is essential for normal fetal growth and to maximize progeny survival and health. However, it is unknown whether GVA function is altered during pregnancy to promote food intake. This study aimed to determine the mechanosensitivity of GVAs and food intake during early, mid-, and late stages of pregnancy in mice. Pregnant mice consumed more food compared with nonpregnant mice, notably in the light phase during mid- and late pregnancy. The increased food intake was predominantly due to light-phase increases in meal size across all stages of pregnancy. The sensitivity of GVA tension receptors to gastric distension was significantly attenuated in mid- and late pregnancy, whereas the sensitivity of GVA mucosal receptors to mucosal stroking was unchanged during pregnancy. To determine whether pregnancy-associated hormonal changes drive these adaptations, the effects of estradiol, progesterone, prolactin, and growth hormone on GVA tension receptor mechanosensitivity were determined in nonpregnant female mice. The sensitivity of GVA tension receptors to gastric distension was augmented by estradiol, attenuated by growth hormone, and unaffected by progesterone or prolactin. Together, the data indicate that the sensitivity of GVA tension receptors to tension is reduced during pregnancy, which may attenuate the perception of gastric fullness and explain increased food intake. Further, these adaptations may be driven by increases in maternal circulating growth hormone levels during pregnancy.NEW & NOTEWORTHY This study provides first evidence that gastric vagal afferent signaling is attenuated during pregnancy and inversely associated with meal size. Growth hormone attenuated mechanosensitivity of gastric vagal afferents, adding support that increases in maternal growth hormone may mediate adaptations in gastric vagal afferent signaling during pregnancy. These findings have important implications for the peripheral control of food intake during pregnancy.


Assuntos
Vias Aferentes/fisiologia , Plasticidade Neuronal/fisiologia , Estômago/inervação , Nervo Vago/fisiologia , Animais , Feminino , Camundongos , Gravidez
14.
Respir Physiol Neurobiol ; 287: 103595, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33309786

RESUMO

Bronchopulmonary mechanosensors play an important role in the regulation of breathing and airway defense. Regarding the mechanosensory unit, investigators have conventionally adhered to 2 doctrines: one-sensor theory (one afferent fiber connects to a single sensor) and line-labeled theory. Accordingly, lung inflation activates 2 types of mechanosensors: slowly adapting receptors (SARs) and rapidly adapting receptors (RARs) that also respond to lung deflation to produce Hering-Breuer deflation reflex. RARs send signals to a particular brain region to stimulate breathing (labeled as excitatory line) and SARs to a different region to inhibit breathing (inhibitory line). Conventionally, RARs are believed to be mechanosensors, but are also stimulated by a variety of chemicals and mediators. They are activated during different disease conditions and evoke various respiratory responses. In the literature, RARs are the most debatable sensors in the airway. Recent physiological and morphological studies demonstrate that a mechanosensory unit consists of numerous sensors with 4 types, i.e., an afferent fiber connects to multiple homogeneous or heterogeneous sensors (multiple-sensor theory). In addition to SARs and RARs, there are deflation-activated receptors (DARs), which can adapt slowly or rapidly. Each type senses a specific force and generates a unique response. For example, RAR (or SAR) units may respond to deflation if they house DARs responsible for the Hering-Breuer deflation reflex. Multiple-sensor theory requires a conceptual shift because 4 different types of information from numerous sensors carried in an afferent pathway violates conventional theories. Data generated over last eight decades under one-sensor theory require re-interpretation. Mechanosensors and their reflex functions need re-definition. This detailed review of the RARs represents our understanding of RARs under the conventional doctrines, thus it provides a very useful background for interpretation of RAR properties and reflex function against the new proposed multiple-sensor theory.


Assuntos
Adaptação Fisiológica/fisiologia , Vias Aferentes/fisiologia , Pneumopatias/fisiopatologia , Receptores Pulmonares de Alongamento/fisiologia , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/fisiopatologia , Animais , Receptores Pulmonares de Alongamento/efeitos dos fármacos , Receptores Pulmonares de Alongamento/fisiopatologia
15.
Gastroenterology ; 160(3): 875-888.e11, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33121946

RESUMO

BACKGROUND AND AIMS: Destroying visceral sensory nerves impacts pancreatic islet function, glucose metabolism, and diabetes onset, but how islet endocrine cells interact with sensory neurons has not been studied. METHODS: We characterized the anatomical pattern of pancreatic sensory innervation by combining viral tracing, immunohistochemistry, and reporter mouse models. To assess the functional interactions of ß-cells with vagal sensory neurons, we recorded Ca2+ responses in individual nodose neurons in vivo while selectively stimulating ß-cells with chemogenetic and pharmacologic approaches. RESULTS: We found that pancreatic islets are innervated by vagal sensory axons expressing Phox2b, substance P, calcitonin-gene related peptide, and the serotonin receptor 5-HT3R. Centrally, vagal neurons projecting to the pancreas terminate in the commissural nucleus of the solitary tract. Nodose neurons responded in vivo to chemogenetic stimulation of ß-cells and to pancreas infusion with serotonin, but were not sensitive to insulin. Responses to chemogenetic and pharmacologic stimulation of ß-cells were blocked by a 5-HT3R antagonist and were enhanced by increasing serotonin levels in ß-cells. We further confirmed directly in living pancreas slices that sensory terminals in the islet were sensitive to serotonin. CONCLUSIONS: Our study establishes that pancreatic ß-cells communicate with vagal sensory neurons, likely using serotonin signaling as a transduction mechanism. Serotonin is coreleased with insulin and may therefore convey information about the secretory state of ß-cells via vagal afferent nerves.


Assuntos
Vias Aferentes/fisiologia , Comunicação Celular , Células Secretoras de Insulina/fisiologia , Gânglio Nodoso/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Feminino , Insulina/metabolismo , Microscopia Intravital , Masculino , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Modelos Animais , Gânglio Nodoso/citologia , Serotonina/metabolismo , Transdução de Sinais/fisiologia
16.
PLoS Genet ; 16(11): e1009120, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33137117

RESUMO

Animals typically avoid unwanted situations with stereotyped escape behavior. For instance, Drosophila larvae often escape from aversive stimuli to the head, such as mechanical stimuli and blue light irradiation, by backward locomotion. Responses to these aversive stimuli are mediated by a variety of sensory neurons including mechanosensory class III da (C3da) sensory neurons and blue-light responsive class IV da (C4da) sensory neurons and Bolwig's organ (BO). How these distinct sensory pathways evoke backward locomotion at the circuit level is still incompletely understood. Here we show that a pair of cholinergic neurons in the subesophageal zone, designated AMBs, evoke robust backward locomotion upon optogenetic activation. Anatomical and functional analysis shows that AMBs act upstream of MDNs, the command-like neurons for backward locomotion. Further functional analysis indicates that AMBs preferentially convey aversive blue light information from C4da neurons to MDNs to elicit backward locomotion, whereas aversive information from BO converges on MDNs through AMB-independent pathways. We also found that, unlike in adult flies, MDNs are dispensable for the dead end-evoked backward locomotion in larvae. Our findings thus reveal the neural circuits by which two distinct blue light-sensing pathways converge on the command-like neurons to evoke robust backward locomotion, and suggest that distinct but partially redundant neural circuits including the command-like neurons might be utilized to drive backward locomotion in response to different sensory stimuli as well as in adults and larvae.


Assuntos
Neurônios Colinérgicos/fisiologia , Drosophila melanogaster/fisiologia , Reação de Fuga/fisiologia , Células Receptoras Sensoriais/fisiologia , Comportamento Estereotipado/fisiologia , Vias Aferentes/fisiologia , Animais , Animais Geneticamente Modificados , Proteínas de Bactérias/genética , Encéfalo/fisiologia , Channelrhodopsins/genética , Proteínas de Drosophila/genética , Reação de Fuga/efeitos da radiação , Feminino , Larva/fisiologia , Luz , Proteínas Luminescentes/genética , Masculino , Optogenética , Comportamento Estereotipado/efeitos da radiação , Fatores de Transcrição/genética
17.
Sci Rep ; 10(1): 18415, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116243

RESUMO

The gastrointestinal tract transmits feeding-regulatory signals to the brain via neuronal and hormonal pathways. Here we studied the interaction between the orexigenic gastric peptide, ghrelin, and the anorectic intestinal peptide, glucagon-like peptide 1 (GLP-1), in terms of feeding regulation via the vagal afferents. GLP-1 preadministration 30 min before ghrelin administration to rats and mice abolished ghrelin-induced food intake, while ghrelin preadministration abolished the anorectic effect of GLP-1. Ghrelin preadministration suppressed GLP-1-induced Fos expression in the nodose ganglia (NG). Electrophysiological assessment confirmed that the initially administered peptide abolished the vagal afferent electrical alteration induced by the subsequently administered peptide. Both the growth hormone secretagogue receptor (GHSR) and the GLP-1 receptor (GLP-1R) are co-localised in a major proportion of NG neurons that innervate the stomach. In these Ghsr+Glp1r+ neurons, ghrelin preadministration abolished the GLP-1-induced calcium response. Ghrelin generated a hyperpolarising current and GLP-1 generated a depolarising current in isolated NG neurons in a patch-clamp experiment. Ghrelin and GLP-1 potently influenced each other in terms of vagally mediated feeding regulation. This peptidergic interaction allows for fine control of the electrophysiological properties of NG neurons.


Assuntos
Vias Aferentes/fisiologia , Regulação do Apetite , Grelina/fisiologia , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Gânglio Nodoso/fisiologia , Animais , Cálcio/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Ratos Wistar , Receptores de Grelina/metabolismo
18.
J Integr Neurosci ; 19(3): 413-420, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070519

RESUMO

Electrical stimulation in the brain is an emerging therapy for treating a wide range of neurological disorders. Although electrical pulses are commonly used in the clinic, other electrical waveforms such as sinusoidal-waves have been investigated to improve the therapeutic efficacy, to reduce the risk of tissue damage induced by stimulation, and to decrease the consumption of electrical energy. However, the effects of sinusoidal stimulation on neuronal activity are still unclear. In the present study, we investigated the neuronal responses to the stimulation of 50-Hz sinusoidal-waves applied on the afferent fibers of the neurons in the hippocampal CA1 region of Sprague-Dawley rat in vivo. Results show that the stimulation increased the firing rate of both pyramidal neurons and interneurons in the downstream region of stimulation. Also, the stimulation eliminated the original theta rhythms (2-5 Hz) in the single-unit activity of the two types of neurons and entrained these neurons to fire at the stimulation rhythm. These results provide new clues for the mechanisms of brain stimulation to suppress the pathological rhythms in the neuronal activity, and for the application of sinusoidal waveforms in brain stimulation therapy.


Assuntos
Vias Aferentes/fisiologia , Região CA1 Hipocampal/fisiologia , Estimulação Elétrica/métodos , Neurônios/fisiologia , Potenciais de Ação , Animais , Axônios/fisiologia , Masculino , Ratos Sprague-Dawley
19.
J Neurosci ; 40(49): 9426-9439, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33115928

RESUMO

The nodose and jugular vagal ganglia supply sensory innervation to the airways and lungs. Jugular vagal airway sensory neurons wire into a brainstem circuit with ascending projections into the submedius thalamic nucleus (SubM) and ventrolateral orbital cortex (VLO), regions known to regulate the endogenous analgesia system. Here we investigate whether the SubM-VLO circuit exerts descending regulation over airway vagal reflexes in male and female rats using a range of neuroanatomical tracing, reflex physiology, and chemogenetic techniques. Anterograde and retrograde neuroanatomical tracing confirmed the connectivity of the SubM and VLO. Laryngeal stimulation in anesthetized rats reduced respiration, a reflex that was potently inhibited by activation of SubM. Conversely, inhibition of SubM potentiated laryngeal reflex responses, while prior lesions of VLO abolished the effects of SubM stimulation. In conscious rats, selective chemogenetic activation of SubM neurons specifically projecting to VLO significantly inhibited respiratory responses evoked by inhalation of the nociceptor stimulant capsaicin. Jugular vagal inputs to SubM via the medullary paratrigeminal nucleus were confirmed using anterograde transsynaptic conditional herpes viral tracing. Respiratory responses evoked by microinjections of capsaicin into the paratrigeminal nucleus were significantly attenuated by SubM stimulation, whereas those evoked via the nucleus of the solitary tract were unaltered. These data suggest that jugular vagal sensory pathways input to a nociceptive thalamocortical circuit capable of regulating jugular sensory processing in the medulla. This circuit organization suggests an intersection between vagal sensory pathways and the endogenous analgesia system, potentially important for understanding vagal sensory processing in health and mechanisms of hypersensitivity in disease.SIGNIFICANCE STATEMENT Jugular vagal sensory pathways are increasingly recognized for their important role in defensive respiratory responses evoked from the airways. Jugular ganglia neurons wire into a central circuit that is notable for overlapping with somatosensory processing networks in the brain rather than the viscerosensory circuits in receipt of inputs from the nodose vagal ganglia. Here we demonstrate a novel and functionally relevant example of intersection between vagal and somatosensory processing in the brain. The findings of the study offer new insights into interactions between vagal and spinal sensory processing, including the medullary targets of the endogenous analgesia system, and offer new insights into the central processes involved in airway defense in health and disease.


Assuntos
Tronco Encefálico/fisiologia , Laringe/fisiologia , Núcleos Posteriores do Tálamo/fisiologia , Sensação/fisiologia , Nervo Vago/fisiologia , Vias Aferentes/fisiologia , Anestesia por Inalação , Animais , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Feminino , Veias Jugulares/inervação , Masculino , Microinjeções , Nociceptores/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Sprague-Dawley , Reflexo/fisiologia , Mecânica Respiratória/fisiologia
20.
J Neurosci ; 40(40): 7714-7723, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32913109

RESUMO

Injury induces synaptic, circuit, and systems reorganization. After unilateral amputation or stroke, this functional loss disrupts the interhemispheric interaction between intact and deprived somatomotor cortices to recruit deprived cortex in response to intact limb stimulation. This recruitment has been implicated in enhanced intact sensory function. In other patients, maladaptive consequences such as phantom limb pain can occur. We used unilateral whisker denervation in male and female mice to detect circuitry alterations underlying interhemispheric cortical reorganization. Enhanced synaptic strength from the intact cortex via the corpus callosum (CC) onto deep neurons in deprived primary somatosensory barrel cortex (S1BC) has previously been detected. It was hypothesized that specificity in this plasticity may depend on to which area these neurons projected. Increased connectivity to somatomotor areas such as contralateral S1BC, primary motor cortex (M1) and secondary somatosensory cortex (S2) may underlie beneficial adaptations, while increased connectivity to pain areas like anterior cingulate cortex (ACC) might underlie maladaptive pain phenotypes. Neurons from the deprived S1BC that project to intact S1BC were hyperexcitable, had stronger responses and reduced inhibitory input to CC stimulation. M1-projecting neurons also showed increases in excitability and CC input strength that was offset with enhanced inhibition. S2 and ACC-projecting neurons showed no changes in excitability or CC input. These results demonstrate that subgroups of output neurons undergo dramatic and specific plasticity after peripheral injury. The changes in S1BC-projecting neurons likely underlie enhanced reciprocal connectivity of S1BC after unilateral deprivation consistent with the model that interhemispheric takeover supports intact whisker processing.SIGNIFICANCE STATEMENT Amputation, peripheral injury, and stroke patients experience widespread alterations in neural activity after sensory loss. A hallmark of this reorganization is the recruitment of deprived cortical space which likely aids processing and thus enhances performance on intact sensory systems. Conversely, this recruitment of deprived cortical space has been hypothesized to underlie phenotypes like phantom limb pain and hinder recovery. A mouse model of unilateral denervation detected remarkable specificity in alterations in the somatomotor circuit. These changes underlie increased reciprocal connectivity between intact and deprived cortical hemispheres. This increased connectivity may help explain the enhanced intact sensory processing detected in humans.


Assuntos
Corpo Caloso/fisiologia , Plasticidade Neuronal , Córtex Somatossensorial/fisiologia , Vibrissas/inervação , Vias Aferentes/citologia , Vias Aferentes/fisiologia , Animais , Corpo Caloso/citologia , Feminino , Lateralidade Funcional , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Córtex Somatossensorial/citologia
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