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1.
Nat Commun ; 12(1): 3916, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168153

RESUMO

Integration of information across the senses is critical for perception and is a common property of neurons in the cerebral cortex, where it is thought to arise primarily from corticocortical connections. Much less is known about the role of subcortical circuits in shaping the multisensory properties of cortical neurons. We show that stimulation of the whiskers causes widespread suppression of sound-evoked activity in mouse primary auditory cortex (A1). This suppression depends on the primary somatosensory cortex (S1), and is implemented through a descending circuit that links S1, via the auditory midbrain, with thalamic neurons that project to A1. Furthermore, a direct pathway from S1 has a facilitatory effect on auditory responses in higher-order thalamic nuclei that project to other brain areas. Crossmodal corticofugal projections to the auditory midbrain and thalamus therefore play a pivotal role in integrating multisensory signals and in enabling communication between different sensory cortical areas.


Assuntos
Córtex Auditivo/fisiologia , Vias Neurais/fisiologia , Córtex Somatossensorial/fisiologia , Estimulação Acústica , Animais , Eletrofisiologia/métodos , Feminino , Neurônios GABAérgicos/fisiologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Interneurônios/fisiologia , Masculino , Mesencéfalo/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Optogenética , Células Receptoras Sensoriais/fisiologia , Córtex Somatossensorial/citologia , Tálamo/citologia , Tálamo/fisiologia
2.
Methods Mol Biol ; 2311: 177-184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34033086

RESUMO

Preparations of peripheral sensory neurons from rodents are essential for studying the molecular mechanism of neuronal survival and physiology. Although, isolating and culturing these neurons proves difficult, often these preparations are contaminated with nonneuronal proliferating cells. Here, we describe an isolation method using a Percoll gradient and an antimitotic reagent to significantly reduce the nonneuronal cell contamination while maintaining the integrity of the rodent sensory dorsal root ganglia (DRG) neurons.


Assuntos
Separação Celular , Gânglios Espinais/embriologia , Células Receptoras Sensoriais/fisiologia , Animais , Técnicas de Cultura de Células , Células Cultivadas , Centrifugação , Idade Gestacional , Camundongos , Povidona/química , Ratos , Dióxido de Silício/química
3.
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
4.
Cell Mol Life Sci ; 78(12): 5069-5082, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33871676

RESUMO

The vomeronasal organ (VNO) is sensory organ located in the ventral region of the nasal cavity in rodents. The VNO develops from the olfactory placode during the secondary invagination of olfactory pit. The embryonic vomeronasal structure appears as a neurogenic area where migratory neuronal populations like endocrine gonadotropin-releasing hormone-1 (GnRH-1) neurons form. Even though embryonic vomeronasal structures are conserved across most vertebrate species, many species including humans do not have a functional VNO after birth. The vomeronasal epithelium (VNE) of rodents is composed of two major types of vomeronasal sensory neurons (VSNs): (1) VSNs distributed in the apical VNE regions that express vomeronasal type-1 receptors (V1Rs) and the G protein subunit Gαi2, and (2) VSNs in the basal territories of the VNE that express vomeronasal type-2 receptors (V2Rs) and the G subunit Gαo. Recent studies identified a third subclass of Gαi2 and Gαo VSNs that express the formyl peptide receptor family. VSNs expressing V1Rs or V2Rs send their axons to distinct regions of the accessory olfactory bulb (AOB). Together, VNO and AOB form the accessory olfactory system (AOS), an olfactory subsystem that coordinates the social and sexual behaviors of many vertebrate species. In this review, we summarize our current understanding of cellular and molecular mechanisms that underlie VNO development. We also discuss open questions for study, which we suggest will further enhance our understanding of VNO morphogenesis at embryonic and postnatal stages.


Assuntos
Morfogênese , Células Receptoras Sensoriais/fisiologia , Órgão Vomeronasal/embriologia , Órgão Vomeronasal/crescimento & desenvolvimento , Animais , Humanos , Células Receptoras Sensoriais/citologia
5.
PLoS Biol ; 19(4): e3001204, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33891586

RESUMO

Many cell types display the remarkable ability to alter their cellular phenotype in response to specific external or internal signals. Such phenotypic plasticity is apparent in the nematode Caenorhabditis elegans when adverse environmental conditions trigger entry into the dauer diapause stage. This entry is accompanied by structural, molecular, and functional remodeling of a number of distinct tissue types of the animal, including its nervous system. The transcription factor (TF) effectors of 3 different hormonal signaling systems, the insulin-responsive DAF-16/FoxO TF, the TGFß-responsive DAF-3/SMAD TF, and the steroid nuclear hormone receptor, DAF-12/VDR, a homolog of the vitamin D receptor (VDR), were previously shown to be required for entering the dauer arrest stage, but their cellular and temporal focus of action for the underlying cellular remodeling processes remained incompletely understood. Through the generation of conditional alleles that allowed us to spatially and temporally control gene activity, we show here that all 3 TFs are not only required to initiate tissue remodeling upon entry into the dauer stage, as shown before, but are also continuously required to maintain the remodeled state. We show that DAF-3/SMAD is required in sensory neurons to promote and then maintain animal-wide tissue remodeling events. In contrast, DAF-16/FoxO or DAF-12/VDR act cell-autonomously to control anatomical, molecular, and behavioral remodeling events in specific cell types. Intriguingly, we also uncover non-cell autonomous function of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling, indicating the presence of several insulin-dependent interorgan signaling axes. Our findings provide novel perspectives into how hormonal systems control tissue remodeling.


Assuntos
Proteínas de Caenorhabditis elegans/fisiologia , Comunicação Celular/genética , Plasticidade Celular/genética , Fatores de Transcrição Forkhead/fisiologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica no Desenvolvimento , Sistema Nervoso/crescimento & desenvolvimento , Sistema Nervoso/metabolismo , Especificidade de Órgãos/genética , Organogênese/genética , Comunicação Parácrina/genética , Receptores de Calcitriol/genética , Receptores de Calcitriol/fisiologia , Receptores Citoplasmáticos e Nucleares/genética , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais/genética
6.
Dev Cell ; 56(7): 976-984.e3, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33823136

RESUMO

Axon remodeling through sprouting and pruning contributes to the refinement of developing neural circuits. A prominent example is the pruning of developing sensory axons deprived of neurotrophic support, which is mediated by a caspase-dependent (apoptotic) degeneration process. Distal sensory axons possess a latent apoptotic pathway, but a cell body-derived signal that travels anterogradely down the axon is required for pathway activation. The signaling mechanisms that underlie this anterograde process are poorly understood. Here, we show that the tumor suppressor P53 is required for anterograde signaling. Interestingly loss of P53 blocks axonal but not somatic (i.e., cell body) caspase activation. Unexpectedly, P53 does not appear to have an acute transcriptional role in this process and instead appears to act in the cytoplasm to directly activate the mitochondrial apoptotic pathway in axons. Our data support the operation of a cytoplasmic role for P53 in the anterograde death of developing sensory axons.


Assuntos
Axônios/fisiologia , Células Receptoras Sensoriais/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Animais , Axônios/enzimologia , Axônios/metabolismo , Caspases/metabolismo , Células Cultivadas , Citoplasma/metabolismo , Camundongos , Domínios Proteicos , Células Receptoras Sensoriais/enzimologia , Células Receptoras Sensoriais/metabolismo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Proteína bcl-X/antagonistas & inibidores
7.
Science ; 372(6540): 385-393, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33888637

RESUMO

Motor and sensory functions of the spinal cord are mediated by populations of cardinal neurons arising from separate progenitor lineages. However, each cardinal class is composed of multiple neuronal types with distinct molecular, anatomical, and physiological features, and there is not a unifying logic that systematically accounts for this diversity. We reasoned that the expansion of new neuronal types occurred in a stepwise manner analogous to animal speciation, and we explored this by defining transcriptomic relationships using a top-down approach. We uncovered orderly genetic tiers that sequentially divide groups of neurons by their motor-sensory, local-long range, and excitatory-inhibitory features. The genetic signatures defining neuronal projections were tied to neuronal birth date and conserved across cardinal classes. Thus, the intersection of cardinal class with projection markers provides a unifying taxonomic solution for systematically identifying distinct functional subsets.


Assuntos
Vias Neurais , Neurônios/fisiologia , Medula Espinal/citologia , Transcriptoma , Animais , Medula Cervical/citologia , Feminino , Masculino , Camundongos , Neurônios Motores/fisiologia , Propriocepção , RNA-Seq , Células Receptoras Sensoriais/fisiologia , Análise de Célula Única , Análise Espacial , Medula Espinal/embriologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
8.
Nat Commun ; 12(1): 2143, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837210

RESUMO

Spiking neural networks (SNNs) promise to bridge the gap between artificial neural networks (ANNs) and biological neural networks (BNNs) by exploiting biologically plausible neurons that offer faster inference, lower energy expenditure, and event-driven information processing capabilities. However, implementation of SNNs in future neuromorphic hardware requires hardware encoders analogous to the sensory neurons, which convert external/internal stimulus into spike trains based on specific neural algorithm along with inherent stochasticity. Unfortunately, conventional solid-state transducers are inadequate for this purpose necessitating the development of neural encoders to serve the growing need of neuromorphic computing. Here, we demonstrate a biomimetic device based on a dual gated MoS2 field effect transistor (FET) capable of encoding analog signals into stochastic spike trains following various neural encoding algorithms such as rate-based encoding, spike timing-based encoding, and spike count-based encoding. Two important aspects of neural encoding, namely, dynamic range and encoding precision are also captured in our demonstration. Furthermore, the encoding energy was found to be as frugal as ≈1-5 pJ/spike. Finally, we show fast (≈200 timesteps) encoding of the MNIST data set using our biomimetic device followed by more than 91% accurate inference using a trained SNN.


Assuntos
Materiais Biomiméticos , Redes Neurais de Computação , Transistores Eletrônicos , Potenciais de Ação/fisiologia , Algoritmos , Biomimética/instrumentação , Conjuntos de Dados como Assunto , Humanos , Rede Nervosa/citologia , Rede Nervosa/fisiologia , Células Receptoras Sensoriais/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia
9.
Nat Commun ; 12(1): 2000, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790301

RESUMO

A crucial role of cortical networks is the conversion of sensory inputs into perception. In the cortical somatosensory network, neurons of the primary somatosensory cortex (S1) show invariant sensory responses, while frontal lobe neuronal activity correlates with the animal's perceptual behavior. Here, we report that in the secondary somatosensory cortex (S2), neurons with invariant sensory responses coexist with neurons whose responses correlate with perceptual behavior. Importantly, the vast majority of the neurons fall along a continuum of combined sensory and categorical dynamics. Furthermore, during a non-demanding control task, the sensory responses remain unaltered while the sensory information exhibits an increase. However, perceptual responses and the associated categorical information decrease, implicating a task context-dependent processing mechanism. Conclusively, S2 neurons exhibit intriguing dynamics that are intermediate between those of S1 and frontal lobe. Our results contribute relevant evidence about the role that S2 plays in the conversion of touch into perception.


Assuntos
Macaca mulatta/fisiologia , Neurônios/fisiologia , Células Receptoras Sensoriais/fisiologia , Córtex Somatossensorial/fisiologia , Percepção do Tato/fisiologia , Algoritmos , Animais , Lobo Frontal/citologia , Lobo Frontal/fisiologia , Modelos Neurológicos , Estimulação Física/métodos , Córtex Somatossensorial/citologia
10.
Elife ; 102021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33759761

RESUMO

Glia in the central nervous system engulf neuron fragments to remodel synapses and recycle photoreceptor outer segments. Whether glia passively clear shed neuronal debris or actively prune neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here, we report our discovery of glia-directed neuron pruning in Caenorhabditis elegans. Adult C. elegans AMsh glia engulf sensory endings of the AFD thermosensory neuron by repurposing components of the conserved apoptotic corpse phagocytosis machinery. The phosphatidylserine (PS) flippase TAT-1/ATP8A functions with glial PS-receptor PSR-1/PSR and PAT-2/α-integrin to initiate engulfment. This activates glial CED-10/Rac1 GTPase through the ternary GEF complex of CED-2/CrkII, CED-5/DOCK180, CED-12/ELMO. Execution of phagocytosis uses the actin-remodeler WSP-1/nWASp. This process dynamically tracks AFD activity and is regulated by temperature, the AFD sensory input. Importantly, glial CED-10 levels regulate engulfment rates downstream of neuron activity, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underlying glia-dependent engulfment in a peripheral sense-organ and demonstrate that glia actively engulf neuron fragments, with profound consequences on neuron shape and animal sensory behavior.


Assuntos
Comportamento Animal/fisiologia , Caenorhabditis elegans/fisiologia , Neuroglia/fisiologia , Fagocitose , Células Receptoras Sensoriais/fisiologia , Animais
11.
Biochem Pharmacol ; 188: 114520, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33741328

RESUMO

Abnormal outgrowth of sensory nerves is one of the important contributors to pain associated with cancer and its treatments. Primary neuronal cultures derived from dorsal root ganglia (DRG) have been widely used to study pain-associated signal transduction and electrical activity of sensory nerves. However, there are only a few studies using primary DRG neuronal culture to investigate neurite outgrowth alterations due to underlying cancer-related factors and chemotherapeutic agents. In this study, primary DRG sensory neurons derived from mouse, non-human primate, and human were established in serum and growth factor-free conditions. A bovine serum albumin gradient centrifugation method improved the separation of sensory neurons from satellite cells. The purified DRG neurons were able to maintain their heterogeneous subpopulations, and displayed an increase in neurite growth when exposed to cancer-derived conditioned medium, while they showed a reduction in neurite length when treated with a neurotoxic chemotherapeutic agent. Additionally, a semi-automated quantification method was developed to measure neurite length in an accurate and time-efficient manner. Finally, these exogenous factors altered the gene expression patterns of murine primary sensory neurons, which are related to nerve growth, and neuro-inflammatory pain and nociceptor development. Together, the primary DRG neuronal culture in combination with a semi-automated quantification method can be a useful tool for further understanding the impact of exogenous factors on the growth of sensory nerve fibers and gene expression changes in sensory neurons.


Assuntos
Dor do Câncer/fisiopatologia , Crescimento Neuronal/fisiologia , Células Receptoras Sensoriais/fisiologia , Células A549 , Adulto , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/etiologia , Carcinoma Pulmonar de Lewis/complicações , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/fisiopatologia , Células Cultivadas , Feminino , Humanos , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Crescimento Neuronal/efeitos dos fármacos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Células Receptoras Sensoriais/efeitos dos fármacos
12.
Clin Neurophysiol ; 132(5): 1157-1162, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33780722

RESUMO

Electrophysiology plays a determinant role in Guillain-Barré syndrome (GBS) diagnosis, classification, and prognostication. However, traditional electrodiagnostic (EDX) criteria for GBS rely on motor nerve conduction studies (NCS) and are suboptimal early in the course of the disease or in the setting of GBS variants. Sensory nerve conduction studies, including the sural-sparing pattern and the sensory ratio are not yet included in EDX criteria despite their well-established role in GBS diagnosis. The aim of this review is to discuss the diagnostic value of sensory NCS in GBS, their role in establishing the diagnosis and predicting the outcome according to the various subtypes of the disease.


Assuntos
Eletrodiagnóstico/métodos , Síndrome de Guillain-Barré/diagnóstico , Condução Nervosa , Células Receptoras Sensoriais/fisiologia , Eletrodiagnóstico/normas , Humanos , Nervos Periféricos/fisiopatologia
13.
Genetics ; 217(1): 1-34, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33683373

RESUMO

Genetic approaches in the fruit fly, Drosophila melanogaster, have led to a major triumph in the field of sensory biology-the discovery of multiple large families of sensory receptors and channels. Some of these families, such as transient receptor potential channels, are conserved from animals ranging from worms to humans, while others, such as "gustatory receptors," "olfactory receptors," and "ionotropic receptors," are restricted to invertebrates. Prior to the identification of sensory receptors in flies, it was widely assumed that these proteins function in just one modality such as vision, smell, taste, hearing, and somatosensation, which includes thermosensation, light, and noxious mechanical touch. By employing a vast combination of genetic, behavioral, electrophysiological, and other approaches in flies, a major concept to emerge is that many sensory receptors are multitaskers. The earliest example of this idea was the discovery that individual transient receptor potential channels function in multiple senses. It is now clear that multitasking is exhibited by other large receptor families including gustatory receptors, ionotropic receptors, epithelial Na+ channels (also referred to as Pickpockets), and even opsins, which were formerly thought to function exclusively as light sensors. Genetic characterizations of these Drosophila receptors and the neurons that express them also reveal the mechanisms through which flies can accurately differentiate between different stimuli even when they activate the same receptor, as well as mechanisms of adaptation, amplification, and sensory integration. The insights gleaned from studies in flies have been highly influential in directing investigations in many other animal models.


Assuntos
Proteínas de Drosophila/metabolismo , Canais Iônicos/metabolismo , Receptores de Superfície Celular/metabolismo , Células Receptoras Sensoriais/metabolismo , Animais , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster , Canais Iônicos/química , Canais Iônicos/genética , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genética , Sensação , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais
14.
Nat Commun ; 12(1): 1789, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741976

RESUMO

Sensory perception and metabolic homeostasis are known to deteriorate with ageing, impairing the health of aged animals, while mechanisms underlying their deterioration remain poorly understood. The potential interplay between the declining sensory perception and the impaired metabolism during ageing is also barely explored. Here, we report that the intraflagellar transport (IFT) in the cilia of sensory neurons is impaired in the aged nematode Caenorhabditis elegans due to a daf-19/RFX-modulated decrease of IFT components. We find that the reduced IFT in sensory cilia thus impairs sensory perception with ageing. Moreover, we demonstrate that whereas the IFT-dependent decrease of sensory perception in aged worms has a mild impact on the insulin/IGF-1 signalling, it remarkably suppresses AMP-activated protein kinase (AMPK) signalling across tissues. We show that upregulating daf-19/RFX effectively enhances IFT, sensory perception, AMPK activity and autophagy, promoting metabolic homeostasis and longevity. Our study determines an ageing pathway causing IFT decay and sensory perception deterioration, which in turn disrupts metabolism and healthy ageing.


Assuntos
Envelhecimento , Caenorhabditis elegans/metabolismo , Cílios/metabolismo , Flagelos/metabolismo , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais/fisiologia , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Animais Geneticamente Modificados , Transporte Biológico , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Longevidade/genética , Percepção/fisiologia , Interferência de RNA , Fator Regulador X1/genética , Fator Regulador X1/metabolismo , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
15.
Nat Commun ; 12(1): 1401, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658516

RESUMO

Effective treatments for patients suffering from heat hypersensitivity are lacking, mostly due to our limited understanding of the pathogenic mechanisms underlying this disorder. In the nervous system, activating transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation. Here, we show that ATF4 plays an important role in heat nociception. Indeed, loss of ATF4 in mouse dorsal root ganglion (DRG) neurons selectively impairs heat sensitivity. Mechanistically, we show that ATF4 interacts with transient receptor potential cation channel subfamily M member-3 (TRPM3) and mediates the membrane trafficking of TRPM3 in DRG neurons in response to heat. Loss of ATF4 also significantly decreases the current and KIF17-mediated trafficking of TRPM3, suggesting that the KIF17/ATF4/TRPM3 complex is required for the neuronal response to heat stimuli. Our findings unveil the non-transcriptional role of ATF4 in the response to heat stimuli in DRG neurons.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Nociceptividade/fisiologia , Células Receptoras Sensoriais/fisiologia , Canais de Cátion TRPM/metabolismo , Fator 4 Ativador da Transcrição/genética , Animais , Membrana Celular/metabolismo , Quimiocina CXCL12/metabolismo , Gânglios Espinais/citologia , Gânglios Espinais/fisiologia , Células HEK293 , Temperatura Alta , Humanos , Injeções Espinhais , Cinesina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Técnicas de Patch-Clamp , Transporte Proteico , Receptores CXCR4/metabolismo , Canais de Cátion TRPM/genética
16.
PLoS One ; 16(2): e0247416, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33617549

RESUMO

Early electroencephalographic studies that focused on finding brain correlates of psychic events led to the discovery of the P300. Since then, the P300 has become the focus of many basic and clinical neuroscience studies. However, despite its wide applications, the underlying function of the P300 is not yet clearly understood. One line of research among the many studies that have attempted to elucidate the underlying subroutine of the P300 in the brain has suggested that the physiological function of the P300 is related to inhibition. While some intracranial, behavioral, and event-related potential studies have provided support for this theory, little is known about the inhibitory mechanism. In this study, using alpha event-related desynchronization (ERD) and effective connectivity, based on the causal (one-way directed) relationship between alpha ERD and P300 sources, we demonstrated that P300's associated inhibition is implemented at a higher information processing stage in a localized brain region. We discuss how inhibition as the primary function of the P300 is not inconsistent with 'resource allocation' and 'working memory updating' theories about its cognitive function. In light of our findings regarding the scope and information processing stage of inhibition of the P300, we reconcile the inhibitory account of the P300 with working memory updating theory. Finally, based on the compensatory behavior of alpha ERD at the time of suppression of the P300, we propose two distinct yet complementary working memory mechanisms (inhibition and desynchronizing excitation) that render target perception possible.


Assuntos
Potencial Evocado P300/fisiologia , Células Receptoras Sensoriais/fisiologia , Vias Visuais/fisiologia , Adulto , Ritmo alfa/fisiologia , Encéfalo/fisiologia , Cognição/fisiologia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Adulto Jovem
17.
Nat Genet ; 53(3): 379-391, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33603234

RESUMO

Rapid cellular responses to environmental stimuli are fundamental for development and maturation. Immediate early genes can be transcriptionally induced within minutes in response to a variety of signals. How their induction levels are regulated and their untimely activation by spurious signals prevented during development is poorly understood. We found that in developing sensory neurons, before perinatal sensory-activity-dependent induction, immediate early genes are embedded into a unique bipartite Polycomb chromatin signature, carrying active H3K27ac on promoters but repressive Ezh2-dependent H3K27me3 on gene bodies. This bipartite signature is widely present in developing cell types, including embryonic stem cells. Polycomb marking of gene bodies inhibits mRNA elongation, dampening productive transcription, while still allowing for fast stimulus-dependent mark removal and bipartite gene induction. We reveal a developmental epigenetic mechanism regulating the rapidity and amplitude of the transcriptional response to relevant stimuli, while preventing inappropriate activation of stimulus-response genes.


Assuntos
Cromatina/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes Precoces , Proteínas do Grupo Polycomb/genética , Animais , Cromatina/metabolismo , Células-Tronco Embrionárias/fisiologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética , Histonas/metabolismo , Camundongos Transgênicos , Mutação , Proteínas do Grupo Polycomb/metabolismo , Regiões Promotoras Genéticas , RNA Polimerase II/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rombencéfalo/efeitos dos fármacos , Rombencéfalo/embriologia , Células Receptoras Sensoriais/fisiologia
18.
Neuron ; 109(7): 1188-1201.e7, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33577748

RESUMO

Proprioception is essential for behavior and provides a sense of our body movements in physical space. Proprioceptor organs are thought to be only in the periphery. Whether the central nervous system can intrinsically sense its own movement remains unclear. Here we identify a segmental organ of proprioception in the adult zebrafish spinal cord, which is embedded by intraspinal mechanosensory neurons expressing Piezo2 channels. These cells are late-born, inhibitory, commissural neurons with unique molecular and physiological profiles reflecting a dual sensory and motor function. The central proprioceptive organ locally detects lateral body movements during locomotion and provides direct inhibitory feedback onto rhythm-generating interneurons responsible for the central motor program. This dynamically aligns central pattern generation with movement outcome for efficient locomotion. Our results demonstrate that a central proprioceptive organ monitors self-movement using hybrid neurons that merge sensory and motor entities into a unified network.


Assuntos
Retroalimentação Sensorial/fisiologia , Movimento/fisiologia , Propriocepção/fisiologia , Peixe-Zebra/fisiologia , Animais , Geradores de Padrão Central/fisiologia , Feminino , Interneurônios/fisiologia , Canais Iônicos/fisiologia , Locomoção/fisiologia , Masculino , Mecanotransdução Celular , Neurônios Motores/fisiologia , Rede Nervosa/citologia , Rede Nervosa/fisiologia , RNA/genética , Células Receptoras Sensoriais/fisiologia , Medula Espinal/diagnóstico por imagem , Medula Espinal/fisiologia , Tomografia Computadorizada por Raios X , Proteínas de Peixe-Zebra/fisiologia
19.
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
20.
Sci Rep ; 11(1): 374, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431991

RESUMO

Regeneration failure after spinal cord injury (SCI) results in part from the lack of a pro-regenerative response in injured neurons, but the response to SCI has not been examined specifically in injured sensory neurons. Using RNA sequencing of dorsal root ganglion, we determined that thoracic SCI elicits a transcriptional response distinct from sciatic nerve injury (SNI). Both SNI and SCI induced upregulation of ATF3 and Jun, yet this response failed to promote growth in sensory neurons after SCI. RNA sequencing of purified sensory neurons one and three days after injury revealed that unlike SNI, the SCI response is not sustained. Both SCI and SNI elicited the expression of ATF3 target genes, with very little overlap between conditions. Pathway analysis of differentially expressed ATF3 target genes revealed that fatty acid biosynthesis and terpenoid backbone synthesis were downregulated after SCI but not SNI. Pharmacologic inhibition of fatty acid synthase, the enzyme generating palmitic acid, decreased axon growth and regeneration in vitro. These results support the notion that decreased expression of lipid metabolism-related genes after SCI, including fatty acid synthase, may restrict axon regenerative capacity after SCI.


Assuntos
Metabolismo dos Lipídeos/genética , Células Receptoras Sensoriais/fisiologia , Traumatismos da Medula Espinal , Animais , Células Cultivadas , Regulação para Baixo/genética , Embrião de Mamíferos , Feminino , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Regeneração Nervosa/genética , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Raízes Nervosas Espinhais/metabolismo , Raízes Nervosas Espinhais/patologia
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