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1.
Nat Commun ; 11(1): 4602, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929071

RESUMO

Human behaviors are extremely sophisticated, relying on the adaptive, plastic and event-driven network of sensory neurons. Such neuronal system analyzes multiple sensory cues efficiently to establish accurate depiction of the environment. Here, we develop a bimodal artificial sensory neuron to implement the sensory fusion processes. Such a bimodal artificial sensory neuron collects optic and pressure information from the photodetector and pressure sensors respectively, transmits the bimodal information through an ionic cable, and integrates them into post-synaptic currents by a synaptic transistor. The sensory neuron can be excited in multiple levels by synchronizing the two sensory cues, which enables the manipulating of skeletal myotubes and a robotic hand. Furthermore, enhanced recognition capability achieved on fused visual/haptic cues is confirmed by simulation of a multi-transparency pattern recognition task. Our biomimetic design has the potential to advance technologies in cyborg and neuromorphic systems by endowing them with supramodal perceptual capabilities.


Assuntos
Células Receptoras Sensoriais/fisiologia , Tato/fisiologia , Visão Ocular/fisiologia , Animais , Linhagem Celular , Eletrodos , Humanos , Camundongos , Movimento (Física) , Nanotubos de Carbono/química , Reconhecimento Automatizado de Padrão
2.
PLoS Comput Biol ; 16(9): e1008146, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32970679

RESUMO

According to the efficient coding hypothesis, sensory systems are adapted to maximize their ability to encode information about the environment. Sensory neurons play a key role in encoding by selectively modulating their firing rate for a subset of all possible stimuli. This pattern of modulation is often summarized via a tuning curve. The optimally efficient distribution of tuning curves has been calculated in variety of ways for one-dimensional (1-D) stimuli. However, many sensory neurons encode multiple stimulus dimensions simultaneously. It remains unclear how applicable existing models of 1-D tuning curves are for neurons tuned across multiple dimensions. We describe a mathematical generalization that builds on prior work in 1-D to predict optimally efficient multidimensional tuning curves. Our results have implications for interpreting observed properties of neuronal populations. For example, our results suggest that not all tuning curve attributes (such as gain and bandwidth) are equally useful for evaluating the encoding efficiency of a population.


Assuntos
Biologia Computacional/métodos , Modelos Neurológicos , Células Receptoras Sensoriais/fisiologia , Encéfalo/fisiologia , Humanos
3.
Science ; 369(6505): 842-846, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32792398

RESUMO

How is neuropathic pain regulated in peripheral sensory neurons? Importins are key regulators of nucleocytoplasmic transport. In this study, we found that importin α3 (also known as karyopherin subunit alpha 4) can control pain responsiveness in peripheral sensory neurons in mice. Importin α3 knockout or sensory neuron-specific knockdown in mice reduced responsiveness to diverse noxious stimuli and increased tolerance to neuropathic pain. Importin α3-bound c-Fos and importin α3-deficient neurons were impaired in c-Fos nuclear import. Knockdown or dominant-negative inhibition of c-Fos or c-Jun in sensory neurons reduced neuropathic pain. In silico screens identified drugs that mimic importin α3 deficiency. These drugs attenuated neuropathic pain and reduced c-Fos nuclear localization. Thus, perturbing c-Fos nuclear import by importin α3 in peripheral neurons can promote analgesia.


Assuntos
Dor Crônica/fisiopatologia , Neuralgia/fisiopatologia , Células Receptoras Sensoriais/fisiologia , alfa Carioferinas/fisiologia , Transporte Ativo do Núcleo Celular , Animais , Benzofenonas/farmacologia , Dor Crônica/genética , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Isoxazóis/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/genética , Proteínas Proto-Oncogênicas c-fos/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-fos/metabolismo , Fator de Transcrição AP-1/metabolismo , alfa Carioferinas/genética
4.
Nat Commun ; 11(1): 4175, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826903

RESUMO

Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.


Assuntos
Neurogênese/genética , Células Receptoras Sensoriais/citologia , Células Receptoras Sensoriais/fisiologia , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Animais , Diferenciação Celular , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/fisiologia , Células-Tronco
5.
PLoS One ; 15(8): e0237440, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790784

RESUMO

We have previously described a novel temporal encoding mechanism in the somatosensory system, where mechanical pulses grouped into periodic bursts create a perceived tactile frequency based on the duration of the silent gap between bursts, rather than the mean rate or the periodicity. This coding strategy may offer new opportunities for transmitting information to the brain using various sensory neural prostheses and haptic interfaces. However, it was not known whether the same coding mechanisms apply when using electrical stimulation, which recruits a different spectrum of afferents. Here, we demonstrate that the predictions of the burst gap coding model for frequency perception apply to burst stimuli delivered with electrical pulses, re-emphasising the importance of the temporal structure of spike patterns in neural processing and perception of tactile stimuli. Reciprocally, the electrical stimulation data confirm that the results observed with mechanical stimulation do indeed depend on neural processing mechanisms in the central nervous system, and are not due to skin mechanical factors and resulting patterns of afferent activation.


Assuntos
Estimulação Elétrica , Percepção do Tato/fisiologia , Potenciais de Ação , Adulto , Axônios/fisiologia , Feminino , Humanos , Masculino , Células Receptoras Sensoriais/fisiologia , Adulto Jovem
6.
Nat Commun ; 11(1): 3689, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32704144

RESUMO

While neurons principally mediate brain function, astrocytes are emerging as cells with important neuromodulatory actions in brain physiology. In addition to homeostatic roles, astrocytes respond to neurotransmitters with calcium transients stimulating the release of gliotransmitters that regulate synaptic and neuronal functions. We investigated astrocyte-neuronal network interactions in vivo by combining two-photon microscopy to monitor astrocyte calcium and electrocorticogram to record neuronal network activity in the somatosensory cortex during sensory stimulation. We found astrocytes respond to sensory stimuli in a stimulus-dependent manner. Sensory stimuli elicit a surge of neuronal network activity in the gamma range (30-50 Hz) followed by a delayed astrocyte activity that dampens the steady-state gamma activity. This sensory-evoked gamma activity increase is enhanced in transgenic mice with impaired astrocyte calcium signaling and is decreased by pharmacogenetic stimulation of astrocytes. Therefore, cortical astrocytes respond to sensory inputs and regulate sensory-evoked neuronal network activity maximizing its dynamic range.


Assuntos
Astrócitos/metabolismo , Rede Nervosa/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Cálcio/metabolismo , Estimulação Elétrica , Feminino , Ritmo Gama/fisiologia , Masculino , Camundongos , Córtex Somatossensorial/citologia
7.
Nat Commun ; 11(1): 2753, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488078

RESUMO

Imbuing bio-inspired sensory devices with intelligent functions of human sensory organs has been limited by challenges in emulating the preprocessing abilities of sensory organs such as reception, filtering, adaptation, and sensory memory at the device level itself. Merkel cells, which is a part of tactile sensory organs, form synapse-like connections with afferent neuron terminals referred to as Merkel cell-neurite complexes. Here, inspired by structure and intelligent functions of Merkel cell-neurite complexes, we report a flexible, artificial, intrinsic-synaptic tactile sensory organ that mimics synapse-like connections using an organic synaptic transistor with ferroelectric nanocomposite gate dielectric of barium titanate nanoparticles and poly(vinylidene fluoride-trifluoroethylene). Modulation of the post-synaptic current of the device induced by ferroelectric dipole switching due to triboelectric-capacitive coupling under finger touch allowed reception and slow adaptation. Modulation of synaptic weight by varying the nanocomposite composition of gate dielectric layer enabled tuning of filtering and sensory memory functions.


Assuntos
Órgãos Artificiais , Células Receptoras Sensoriais/fisiologia , Tato/fisiologia , Técnicas Biossensoriais/instrumentação , Humanos , Aprendizagem/fisiologia , Memória/fisiologia , Células de Merkel , Neuritos , Sinapses/fisiologia , Percepção do Tato , Transistores Eletrônicos
8.
Nat Commun ; 11(1): 2076, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350283

RESUMO

Learning and memory are regulated by neuromodulatory pathways, but the contribution and temporal requirement of most neuromodulators in a learning circuit are unknown. Here we identify the evolutionarily conserved neuromedin U (NMU) neuropeptide family as a regulator of C. elegans gustatory aversive learning. The NMU homolog CAPA-1 and its receptor NMUR-1 are required for the retrieval of learned salt avoidance. Gustatory aversive learning requires the release of CAPA-1 neuropeptides from sensory ASG neurons that respond to salt stimuli in an experience-dependent manner. Optogenetic silencing of CAPA-1 neurons blocks the expression, but not the acquisition, of learned salt avoidance. CAPA-1 signals through NMUR-1 in AFD sensory neurons to modulate two navigational strategies for salt chemotaxis. Aversive conditioning thus recruits NMU signaling to modulate locomotor programs for expressing learned avoidance behavior. Because NMU signaling is conserved across bilaterian animals, our findings incite further research into its function in other learning circuits.


Assuntos
Aprendizagem da Esquiva/fisiologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Rede Nervosa/fisiologia , Neuropeptídeos/metabolismo , Transdução de Sinais , Cloreto de Sódio/efeitos adversos , Paladar/fisiologia , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Comportamento Animal , Proteínas de Caenorhabditis elegans/química , Cálcio/metabolismo , Alimentos , Modelos Biológicos , Mutação/genética , Filogenia , Células Receptoras Sensoriais/fisiologia
9.
Nat Commun ; 11(1): 2675, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32472088

RESUMO

Abnormal sensory processing has been observed in autism, including superior visual motion discrimination, but the neural basis for these sensory changes remains unknown. Leveraging well-characterized suppressive neural circuits in the visual system, we used behavioral and fMRI tasks to demonstrate a significant reduction in neural suppression in young adults with autism spectrum disorder (ASD) compared to neurotypical controls. MR spectroscopy measurements revealed no group differences in neurotransmitter signals. We show how a computational model that incorporates divisive normalization, as well as narrower top-down gain (that could result, for example, from a narrower window of attention), can explain our observations and divergent previous findings. Thus, weaker neural suppression is reflected in visual task performance and fMRI measures in ASD, and may be attributable to differences in top-down processing.


Assuntos
Transtorno Autístico/patologia , Percepção de Movimento/fisiologia , Acuidade Visual/fisiologia , Adolescente , Adulto , Atenção/fisiologia , Mapeamento Encefálico , Cognição/fisiologia , Simulação por Computador , Discriminação Psicológica/fisiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Células Receptoras Sensoriais/fisiologia , Adulto Jovem
10.
Nature ; 580(7801): 100-105, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238928

RESUMO

How the brain processes information accurately despite stochastic neural activity is a longstanding question1. For instance, perception is fundamentally limited by the information that the brain can extract from the noisy dynamics of sensory neurons. Seminal experiments2,3 suggest that correlated noise in sensory cortical neural ensembles is what limits their coding accuracy4-6, although how correlated noise affects neural codes remains debated7-11. Recent theoretical work proposes that how a neural ensemble's sensory tuning properties relate statistically to its correlated noise patterns is a greater determinant of coding accuracy than is absolute noise strength12-14. However, without simultaneous recordings from thousands of cortical neurons with shared sensory inputs, it is unknown whether correlated noise limits coding fidelity. Here we present a 16-beam, two-photon microscope to monitor activity across the mouse primary visual cortex, along with analyses to quantify the information conveyed by large neural ensembles. We found that, in the visual cortex, correlated noise constrained signalling for ensembles with 800-1,300 neurons. Several noise components of the ensemble dynamics grew proportionally to the ensemble size and the encoded visual signals, revealing the predicted information-limiting correlations12-14. Notably, visual signals were perpendicular to the largest noise mode, which therefore did not limit coding fidelity. The information-limiting noise modes were approximately ten times smaller and concordant with mouse visual acuity15. Therefore, cortical design principles appear to enhance coding accuracy by restricting around 90% of noise fluctuations to modes that do not limit signalling fidelity, whereas much weaker correlated noise modes inherently bound sensory discrimination.


Assuntos
Células Receptoras Sensoriais/fisiologia , Acuidade Visual/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Animais , Feminino , Masculino , Camundongos , Estimulação Luminosa , Processos Estocásticos
11.
Cell Prolif ; 53(5): e12803, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32246537

RESUMO

OBJECTIVES: The aim of this study is to investigate the role of sensory nerve in tooth homeostasis and its effect on mesenchymal stromal/stem cells (MSCs) in dental pulp. MATERIALS AND METHODS: We established the rat denervated incisor models to identify the morphological and histological changes of tooth. The groups were as follows: IANx (inferior alveolar nerve section), SCGx (superior cervical ganglion removal), IANx + SCGx and Sham group. The biological behaviour of dental pulp stromal/stem cells (DPSCs) was evaluated. Finally, we applied activin B to DPSCs from sensory nerve-deficient microenvironment to analyse the changes of proliferation and apoptosis. RESULTS: Incisor of IANx and IANx + SCGx groups exhibited obvious disorganized tooth structure, while SCGx group only showed slight decrease of dentin thickness, implying sensory nerve, not sympathetic nerve, contributes to the tooth homeostasis. Moreover, we found sensory nerve injury led to disfunction of DPSCs via activin B/SMAD2/3 signalling in vitro. Supplementing activin B promoted proliferation and reduced apoptosis of DPSCs in sensory nerve-deficient microenvironment. CONCLUSIONS: This research first demonstrates that sensory nerve-deficient microenvironment impairs tooth haemostasis by inducing apoptosis of DPSCs via activin B/SMAD2/3 signalling. Our study provides the evidence for the crucial role of sensory nerve in tooth homeostasis.


Assuntos
Apoptose/fisiologia , Polpa Dentária/fisiologia , Homeostase/fisiologia , Células Receptoras Sensoriais/fisiologia , Células-Tronco/fisiologia , Dente/fisiologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Microambiente Celular/fisiologia , Técnicas de Cocultura/métodos , Polpa Dentária/metabolismo , Dentina/metabolismo , Dentina/fisiologia , Feminino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo , Dente/metabolismo
13.
Nat Rev Gastroenterol Hepatol ; 17(6): 338-351, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32152479

RESUMO

The gastrointestinal tract is the only internal organ to have evolved with its own independent nervous system, known as the enteric nervous system (ENS). This Review provides an update on advances that have been made in our understanding of how neurons within the ENS coordinate sensory and motor functions. Understanding this function is critical for determining how deficits in neurogenic motor patterns arise. Knowledge of how distension or chemical stimulation of the bowel evokes sensory responses in the ENS and central nervous system have progressed, including critical elements that underlie the mechanotransduction of distension-evoked colonic peristalsis. Contrary to original thought, evidence suggests that mucosal serotonin is not required for peristalsis or colonic migrating motor complexes, although it can modulate their characteristics. Chemosensory stimuli applied to the lumen can release substances from enteroendocrine cells, which could subsequently modulate ENS activity. Advances have been made in optogenetic technologies, such that specific neurochemical classes of enteric neurons can be stimulated. A major focus of this Review will be the latest advances in our understanding of how intrinsic sensory neurons in the ENS detect and respond to sensory stimuli and how these mechanisms differ from extrinsic sensory nerve endings in the gut that underlie the gut-brain axis.


Assuntos
Sistema Nervoso Entérico/fisiologia , Motilidade Gastrointestinal/fisiologia , Sensação/fisiologia , Células Receptoras Sensoriais/fisiologia , Vias Aferentes/fisiologia , Fibras Autônomas Pré-Ganglionares/fisiologia , Vias Eferentes/fisiologia , Sistema Nervoso Entérico/metabolismo , Células Enteroendócrinas/metabolismo , Células Enteroendócrinas/fisiologia , Humanos , Mecanotransdução Celular/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Vias Neurais/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Neurotransmissores/metabolismo , Células Receptoras Sensoriais/metabolismo , Serotonina/metabolismo
14.
PLoS Comput Biol ; 16(2): e1007526, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32027645

RESUMO

We approach the C. elegans connectome as an information processing network that receives input from about 90 sensory neurons, processes that information through a highly recurrent network of about 80 interneurons, and it produces a coordinated output from about 120 motor neurons that control the nematode's muscles. We focus on the feedforward flow of information from sensory neurons to motor neurons, and apply a recently developed network analysis framework referred to as the "hourglass effect". The analysis reveals that this feedforward flow traverses a small core ("hourglass waist") that consists of 10-15 interneurons. These are mostly the same interneurons that were previously shown (using a different analytical approach) to constitute the "rich-club" of the C. elegans connectome. This result is robust to the methodology that separates the feedforward from the feedback flow of information. The set of core interneurons remains mostly the same when we consider only chemical synapses or the combination of chemical synapses and gap junctions. The hourglass organization of the connectome suggests that C. elegans has some similarities with encoder-decoder artificial neural networks in which the input is first compressed and integrated in a low-dimensional latent space that encodes the given data in a more efficient manner, followed by a decoding network through which intermediate-level sub-functions are combined in different ways to compute the correlated outputs of the network. The core neurons at the hourglass waist represent the information bottleneck of the system, balancing the representation accuracy and compactness (complexity) of the given sensory information.


Assuntos
Caenorhabditis elegans/fisiologia , Conectoma , Animais , Biologia Computacional , Junções Comunicantes/fisiologia , Interneurônios/fisiologia , Neurônios Motores/fisiologia , Células Receptoras Sensoriais/fisiologia , Sinapses/fisiologia
15.
16.
Nat Commun ; 11(1): 746, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029727

RESUMO

Stimuli are represented in the brain by the collective population responses of sensory neurons, and an object presented under varying conditions gives rise to a collection of neural population responses called an 'object manifold'. Changes in the object representation along a hierarchical sensory system are associated with changes in the geometry of those manifolds, and recent theoretical progress connects this geometry with 'classification capacity', a quantitative measure of the ability to support object classification. Deep neural networks trained on object classification tasks are a natural testbed for the applicability of this relation. We show how classification capacity improves along the hierarchies of deep neural networks with different architectures. We demonstrate that changes in the geometry of the associated object manifolds underlie this improved capacity, and shed light on the functional roles different levels in the hierarchy play to achieve it, through orchestrated reduction of manifolds' radius, dimensionality and inter-manifold correlations.


Assuntos
Modelos Neurológicos , Redes Neurais de Computação , Percepção Visual/fisiologia , Algoritmos , Encéfalo/fisiologia , Aprendizado Profundo , Humanos , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa , Células Receptoras Sensoriais/fisiologia
17.
Nat Commun ; 11(1): 872, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054847

RESUMO

Natural scenes sparsely activate neurons in the primary visual cortex (V1). However, how sparsely active neurons reliably represent complex natural images and how the information is optimally decoded from these representations have not been revealed. Using two-photon calcium imaging, we recorded visual responses to natural images from several hundred V1 neurons and reconstructed the images from neural activity in anesthetized and awake mice. A single natural image is linearly decodable from a surprisingly small number of highly responsive neurons, and the remaining neurons even degrade the decoding. Furthermore, these neurons reliably represent the image across trials, regardless of trial-to-trial response variability. Based on our results, diverse, partially overlapping receptive fields ensure sparse and reliable representation. We suggest that information is reliably represented while the corresponding neuronal patterns change across trials and collecting only the activity of highly responsive neurons is an optimal decoding strategy for the downstream neurons.


Assuntos
Células Receptoras Sensoriais/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Animais , Feminino , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa
18.
PLoS Genet ; 16(2): e1008626, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32059017

RESUMO

Neuronal pruning is a commonly observed phenomenon for the developing nervous systems to ensure precise wiring of neural circuits. The function of Ik2 kinase and its downstream mediator, Spindle-F (Spn-F), are essential for dendrite pruning of Drosophila sensory neurons during development. However, little is known about how Ik2/Spn-F signaling is transduced in neurons and ultimately results in dendrite pruning. Our genetic analyses and rescue experiments demonstrated that the small GTPase Rab11, especially the active GTP-bound form, is required for dendrite pruning. We also found that Rab11 shows genetic interactions with spn-F and ik2 on pruning. Live imaging of single neurons and antibody staining reveal normal Ik2 kinase activation in Rab11 mutant neurons, suggesting that Rab11 could have a functional connection downstream of and/or parallel to the Ik2 kinase signaling. Moreover, we provide biochemical evidence that both the Ik2 kinase activity and the formation of Ik2/Spn-F/Rab11 complexes are central to promote Rab11 activation in cells. Together, our studies reveal that a critical role of Ik2/Spn-F signaling in neuronal pruning is to promote Rab11 activation, which is crucial for dendrite pruning in neurons.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Quinase I-kappa B/metabolismo , Plasticidade Neuronal/genética , Células Receptoras Sensoriais/fisiologia , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Animais Geneticamente Modificados , Linhagem Celular , Dendritos/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Embrião não Mamífero , Técnicas de Silenciamento de Genes , Microscopia Intravital , Proteínas Associadas aos Microtúbulos/metabolismo , Células Receptoras Sensoriais/citologia , Transdução de Sinais/fisiologia , Imagem com Lapso de Tempo , Proteínas rab de Ligação ao GTP/genética
19.
PLoS Genet ; 16(2): e1008589, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32059010

RESUMO

Nervous systems have the ability to select appropriate actions and action sequences in response to sensory cues. The circuit mechanisms by which nervous systems achieve choice, stability and transitions between behaviors are still incompletely understood. To identify neurons and brain areas involved in controlling these processes, we combined a large-scale neuronal inactivation screen with automated action detection in response to a mechanosensory cue in Drosophila larva. We analyzed behaviors from 2.9x105 larvae and identified 66 candidate lines for mechanosensory responses out of which 25 for competitive interactions between actions. We further characterize in detail the neurons in these lines and analyzed their connectivity using electron microscopy. We found the neurons in the mechanosensory network are located in different regions of the nervous system consistent with a distributed model of sensorimotor decision-making. These findings provide the basis for understanding how selection and transition between behaviors are controlled by the nervous system.


Assuntos
Potenciais de Ação/fisiologia , Ligação Competitiva , Mecanotransdução Celular/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Células Receptoras Sensoriais/fisiologia , Transmissão Sináptica/fisiologia , Animais , Animais Geneticamente Modificados , Ligação Competitiva/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Mapeamento Encefálico , Sinais (Psicologia) , Drosophila melanogaster/genética , Vias Neurais/metabolismo , Neurônios/metabolismo , Fenótipo
20.
Proc Natl Acad Sci U S A ; 117(10): 5494-5501, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32079727

RESUMO

Somatosensory neurons have historically been classified by a variety of approaches, including structural, anatomical, and genetic markers; electrophysiological properties; pharmacological sensitivities; and more recently, transcriptional profile differentiation. These methodologies, used separately, have yielded inconsistent classification schemes. Here, we describe phenotypic differences in response to pharmacological agents as measured by changes in cytosolic calcium concentration for the rapid classification of neurons in vitro; further analysis with genetic markers, whole-cell recordings, and single-cell transcriptomics validated these findings in a functional context. Using this general approach, which we refer to as tripartite constellation analysis (TCA), we focused on large-diameter dorsal-root ganglion (L-DRG) neurons with myelinated axons. Divergent responses to the K-channel antagonist, κM-conopeptide RIIIJ (RIIIJ), reliably identified six discrete functional cell classes. In two neuronal subclasses (L1 and L2), block with RIIIJ led to an increase in [Ca] i Simultaneous electrophysiology and calcium imaging showed that the RIIIJ-elicited increase in [Ca] i corresponded to different patterns of action potentials (APs), a train of APs in L1 neurons, and sporadic firing in L2 neurons. Genetically labeled mice established that L1 neurons are proprioceptors. The single-cell transcriptomes of L1 and L2 neurons showed that L2 neurons are Aδ-low-threshold mechanoreceptors. RIIIJ effects were replicated by application of the Kv1.1 selective antagonist, Dendrotoxin-K, in several L-DRG subclasses (L1, L2, L3, and L5), suggesting the presence of functional Kv1.1/Kv1.2 heteromeric channels. Using this approach on other neuronal subclasses should ultimately accelerate the comprehensive classification and characterization of individual somatosensory neuronal subclasses within a mixed population.


Assuntos
Gânglios Espinais/citologia , Células Receptoras Sensoriais/classificação , Células Receptoras Sensoriais/fisiologia , Animais , Cálcio/metabolismo , Conotoxinas/farmacologia , Citosol/metabolismo , Gânglios Espinais/efeitos dos fármacos , Canal de Potássio Kv1.1/antagonistas & inibidores , Camundongos , Camundongos Transgênicos , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Células Receptoras Sensoriais/efeitos dos fármacos , Análise de Célula Única , Transcriptoma
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