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1.
Nat Neurosci ; 23(3): 337-350, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32112058

RESUMO

Tissue repair after spinal cord injury requires the mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core, which is surrounded by an astrocytic border. Here we elucidate a temporally distinct gene signature in injury-activated microglia and macrophages (IAMs) that engages axon guidance pathways. Plexin-B2 is upregulated in IAMs and is required for motor sensory recovery after spinal cord injury. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAMs away from colliding cells and facilitates matrix compaction. Our data therefore establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAMs with the injury microenvironment during wound healing.


Assuntos
Macrófagos/fisiologia , Microglia/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Traumatismos da Medula Espinal/patologia , Cicatrização/fisiologia , Animais , Axônios/fisiologia , Microambiente Celular , Locomoção/fisiologia , Camundongos , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Vias Neurais/fisiologia , Fagocitose , Recuperação de Função Fisiológica , Sensação/fisiologia , Traumatismos da Medula Espinal/metabolismo
2.
PLoS Biol ; 18(2): e3000361, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32078631

RESUMO

Sleep-active neurons depolarize during sleep to suppress wakefulness circuits. Wake-active wake-promoting neurons in turn shut down sleep-active neurons, thus forming a bipartite flip-flop switch. However, how sleep is switched on is unclear because it is not known how wakefulness is translated into sleep-active neuron depolarization when the system is set to sleep. Using optogenetics in Caenorhabditis elegans, we solved the presynaptic circuit for depolarization of the sleep-active RIS neuron during developmentally regulated sleep, also known as lethargus. Surprisingly, we found that RIS activation requires neurons that have known roles in wakefulness and locomotion behavior. The RIM interneurons-which are active during and can induce reverse locomotion-play a complex role and can act as inhibitors of RIS when they are strongly depolarized and as activators of RIS when they are modestly depolarized. The PVC command interneurons, which are known to promote forward locomotion during wakefulness, act as major activators of RIS. The properties of these locomotion neurons are modulated during lethargus. The RIMs become less excitable. The PVCs become resistant to inhibition and have an increased capacity to activate RIS. Separate activation of neither the PVCs nor the RIMs appears to be sufficient for sleep induction; instead, our data suggest that they act in concert to activate RIS. Forward and reverse circuit activity is normally mutually exclusive. Our data suggest that RIS may be activated at the transition between forward and reverse locomotion states, perhaps when both forward (PVC) and reverse (including RIM) circuit activity overlap. While RIS is not strongly activated outside of lethargus, altered activity of the locomotion interneurons during lethargus favors strong RIS activation and thus sleep. The control of sleep-active neurons by locomotion circuits suggests that sleep control may have evolved from locomotion control. The flip-flop sleep switch in C. elegans thus requires an additional component, wake-active sleep-promoting neurons that translate wakefulness into the depolarization of a sleep-active neuron when the worm is sleepy. Wake-active sleep-promoting circuits may also be required for sleep state switching in other animals, including in mammals.


Assuntos
Locomoção/fisiologia , Neurônios/fisiologia , Fases do Sono/fisiologia , Vigília/fisiologia , Animais , Nível de Alerta/fisiologia , Comportamento Animal/fisiologia , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Cálcio/metabolismo , Homeostase , Interneurônios/metabolismo , Interneurônios/fisiologia , Larva/fisiologia , Vias Neurais/fisiologia , Neurônios/metabolismo , Optogenética
3.
Nat Commun ; 11(1): 262, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937768

RESUMO

Navigation requires not only the execution of locomotor programs but also high arousal and real-time retrieval of spatial memory that is often associated with hippocampal theta oscillations. However, the neural circuits for coordinately controlling these important processes remain to be fully dissected. Here we show that the activity of the neuromedin B (NMB) neurons in the nucleus incertus (NI) is tightly correlated with mouse locomotor speed, arousal level, and hippocampal theta power. These processes are reversibly suppressed by optogenetic inhibition and rapidly promoted by optogenetic stimulation of NI NMB neurons. These neurons form reciprocal connections with several subcortical areas associated with arousal, theta oscillation, and premotor processing. Their projections to multiple downstream stations regulate locomotion and hippocampal theta, with the projection to the medial septum being particularly important for promoting arousal. Therefore, NI NMB neurons functionally impact the neural circuit for navigation control according to particular brains states.


Assuntos
Nível de Alerta/fisiologia , Hipocampo/fisiologia , Locomoção/fisiologia , Núcleos da Rafe/fisiologia , Animais , Feminino , Masculino , Camundongos , Vias Neurais/fisiologia , Neurocinina B/análogos & derivados , Neurocinina B/metabolismo , Neurônios/metabolismo , Optogenética , Núcleos da Rafe/citologia , Septo do Cérebro/fisiologia , Navegação Espacial/fisiologia , Ritmo Teta
4.
PLoS Comput Biol ; 16(1): e1007591, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999693

RESUMO

To develop a complete description of sensory encoding, it is necessary to account for trial-to-trial variability in cortical neurons. Using a linear model with terms corresponding to the visual stimulus, mouse running speed, and experimentally measured neuronal correlations, we modeled short term dynamics of L2/3 murine visual cortical neurons to evaluate the relative importance of each factor to neuronal variability within single trials. We find single trial predictions improve most when conditioning on the experimentally measured local correlations in comparison to predictions based on the stimulus or running speed. Specifically, accurate predictions are driven by positively co-varying and synchronously active functional groups of neurons. Including functional groups in the model enhances decoding accuracy of sensory information compared to a model that assumes neuronal independence. Functional groups, in encoding and decoding frameworks, provide an operational definition of Hebbian assemblies in which local correlations largely explain neuronal responses on individual trials.


Assuntos
Modelos Neurológicos , Neurônios , Estimulação Luminosa , Córtex Visual , Animais , Biologia Computacional , Feminino , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia
5.
PLoS One ; 15(1): e0228044, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978202

RESUMO

BACKGROUND: Locomotion is an energy costly behaviour, particularly when it entails raising weight against gravity. Minimization of locomotor costs appears a universal default. Avoidance of stair climbing helps humans minimise their energetic costs. In public access settings, demographic subgroups that raise more 'dead' weight than their comparison groups when climbing are more likely to avoid stairs by choosing the escalator. Individuals who minimise stair costs at work, however, can accumulate a deficit in energy expenditure in daily life with potential implications for weight gain. This paper tests the generality of avoidance of stairs in pedestrians encumbered by additional weight in three studies. METHODS: Pedestrian choices for stairs or the alternative were audited by trained observers who coded weight status, presence of large bags and sex for each pedestrian. Sex-specific silhouettes for BMIs of 25 facilitated coding of weight status. Choices between stairs and a lift to ascend and descend were coded in seven buildings (n = 26,981) and at an outdoor city centre site with the same alternatives (n = 7,433). A further study audited choices to ascend when the alternative to stairs was a sloped ramp in two locations (n = 16,297). Analyses employed bootstrapped logistic regression (1000 samples). RESULTS: At work and the city centre site, the overweight, those carrying a large bag and females avoided both stair climbing and descent more frequently than their comparison groups. The final study revealed greater avoidance of stairs in these demographic subgroups when the alternative means of ascent was a sloped ramp. DISCUSSION: Minimization of the physiological costs of transport-related walking biases behaviour towards avoidance of stair usage when an alternative is available. Weight carried is an encumbrance that can deter stair usage during daily life. This minimization of physical activity costs runs counter to public health initiatives to increase activity to improve population health.


Assuntos
Peso Corporal/fisiologia , Demografia , Locomoção/fisiologia , Feminino , Humanos , Masculino , Local de Trabalho
6.
PLoS One ; 15(1): e0224715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914121

RESUMO

Habits are automated behaviors that are insensitive to changes in behavioral outcomes. Habitual responding is thought to be mediated by the striatum, with medial striatum guiding goal-directed action and lateral striatum promoting habits. However, interspersed throughout the striatum are neurochemically differing subcompartments known as patches, which are characterized by distinct molecular profiles relative to the surrounding matrix tissue. These structures have been thoroughly characterized neurochemically and anatomically, but little is known regarding their function. Patches have been shown to be selectively activated during inflexible motor stereotypies elicited by stimulants, suggesting that patches may subserve habitual behaviors. To explore this possibility, we utilized transgenic mice (Sepw1 NP67) preferentially expressing Cre recombinase in striatal patch neurons to target these neurons for ablation with a virus driving Cre-dependent expression of caspase 3. Mice were then trained to press a lever for sucrose rewards on a variable interval schedule to elicit habitual responding. Mice were not impaired on the acquisition of this task, but lesioning striatal patches disrupted behavioral stability across training, and lesioned mice utilized a more goal-directed behavioral strategy during training. Similarly, when mice were forced to omit responses to receive sucrose rewards, habitual responding was impaired in lesioned mice. To rule out effects of lesion on motor behaviors, mice were then tested for impairments in motor learning on a rotarod and locomotion in an open field. We found that patch lesions partially impaired initial performance on the rotarod without modifying locomotor behaviors in open field. This work indicates that patches promote behavioral stability and habitual responding, adding to a growing literature implicating striatal patches in stimulus-response behaviors.


Assuntos
Comportamento Animal/fisiologia , Corpo Estriado/fisiologia , Neostriado/fisiologia , Neurônios/fisiologia , Animais , Caspase 3/genética , Estimulantes do Sistema Nervoso Central/farmacologia , Dopamina/metabolismo , Hábitos , Integrases/genética , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Motivação/genética , Motivação/fisiologia , Selenoproteína W
7.
Proc Natl Acad Sci U S A ; 117(1): 278-284, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871170

RESUMO

Oreopithecus bambolii (8.3-6.7 million years old) is the latest known hominoid from Europe, dating to approximately the divergence time of the Pan-hominin lineages. Despite being the most complete nonhominin hominoid in the fossil record, the O. bambolii skeleton IGF 11778 has been, for decades, at the center of intense debate regarding the species' locomotor behavior, phylogenetic position, insular paleoenvironment, and utility as a model for early hominin anatomy. Here we investigate features of the IGF 11778 pelvis and lumbar region based on torso preparations and supplemented by other O. bambolii material. We correct several crucial interpretations relating to the IGF 11778 anterior inferior iliac spine and lumbar vertebrae structure and identifications. We find that features of the early hominin Ardipithecus ramidus torso that are argued to have permitted both lordosis and pelvic stabilization during upright walking are not present in O. bambolii However, O. bambolii also lacks the complete reorganization for torso stiffness seen in extant great apes (i.e., living members of the Hominidae), and is more similar to large hylobatids in certain aspects of torso form. We discuss the major implications of the O. bambolii lower torso anatomy and how O. bambolii informs scenarios of hominoid evolution.


Assuntos
Fósseis , Hominidae/anatomia & histologia , Hominidae/classificação , Filogenia , Tronco/anatomia & histologia , Animais , Evolução Biológica , Hominidae/fisiologia , Humanos , Locomoção/fisiologia , Lordose , Vértebras Lombares/anatomia & histologia , Pelve/anatomia & histologia , Caminhada/fisiologia
8.
Proc Natl Acad Sci U S A ; 117(1): 472-478, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871184

RESUMO

The unique engulfment filtration strategy of microphagous rorqual whales has evolved relatively recently (<5 Ma) and exploits extreme predator/prey size ratios to overcome the maneuverability advantages of swarms of small prey, such as krill. Forage fish, in contrast, have been engaged in evolutionary arms races with their predators for more than 100 million years and have performance capabilities that suggest they should easily evade whale-sized predators, yet they are regularly hunted by some species of rorqual whales. To explore this phenomenon, we determined, in a laboratory setting, when individual anchovies initiated escape from virtually approaching whales, then used these results along with in situ humpback whale attack data to model how predator speed and engulfment timing affected capture rates. Anchovies were found to respond to approaching visual looming stimuli at expansion rates that give ample chance to escape from a sea lion-sized predator, but humpback whales could capture as much as 30-60% of a school at once because the increase in their apparent (visual) size does not cross their prey's response threshold until after rapid jaw expansion. Humpback whales are, thus, incentivized to delay engulfment until they are very close to a prey school, even if this results in higher hydrodynamic drag. This potential exaptation of a microphagous filter feeding strategy for fish foraging enables humpback whales to achieve 7× the energetic efficiency (per lunge) of krill foraging, allowing for flexible foraging strategies that may underlie their ecological success in fluctuating oceanic conditions.


Assuntos
Reação de Fuga/fisiologia , Comportamento Alimentar , Peixes/fisiologia , Jubarte/fisiologia , Comportamento Predatório/fisiologia , Animais , Evolução Biológica , Euphausiacea/fisiologia , Filtração , Jubarte/anatomia & histologia , Hidrodinâmica , Arcada Osseodentária/anatomia & histologia , Locomoção/fisiologia , Modelos Biológicos , Tamanho do Órgão/fisiologia , Fatores de Tempo
9.
Nat Commun ; 10(1): 5815, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31862889

RESUMO

Locomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.


Assuntos
Locomoção/fisiologia , Neurônios Motores/fisiologia , Fatores de Crescimento Neural/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Atrofia/patologia , Atrofia/fisiopatologia , Dendritos/patologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neurônios Motores/patologia , Vias Neurais/fisiopatologia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/patologia
10.
Int Rev Neurobiol ; 147: 199-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607355

RESUMO

Body-weight-supported locomotor training is an activity-based therapy used frequently to train individuals with spinal cord injury (SCI) for restoring walking ability. Locomotor training after SCI is developed on the basic scientific findings of activity-dependent neuroplasticity. Based on the research from animal SCI models, there exists a spinal neural networks for locomotion which can be reactivated by intense repetitive locomotor training. Notably, the effectiveness of locomotor training depends largely on the severity of injury and time after injury. Locomotor training, using body-weight-supported walking overground or on a treadmill, with assistance manually or robotically, with a variety of training intensity and training programs, has been shown to elicit improvements in locomotor function for incomplete SCI individuals. For chronic and motor complete SCI, other interventions with proven effectiveness such as epidural stimulation might be applied in addition to locomotor training to improve the chance of locomotor recovery. In this chapter, we review the factors that influence the functional outcomes of locomotor training. We also summarize the circuitry, cellular and molecular levels of mechanisms underlying the positive role of locomotor training in inducing neuroplasticity and functional recovery following SCI.


Assuntos
Locomoção/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Medula Espinal/fisiologia , Animais , Humanos
11.
PLoS Biol ; 17(10): e3000511, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31603894

RESUMO

Cognitive processes are almost exclusively investigated under highly controlled settings during which voluntary body movements are suppressed. However, recent animal work suggests differences in sensory processing between movement states by showing drastically changed neural responses in early visual areas between locomotion and stillness. Does locomotion also modulate visual cortical activity in humans, and what are the perceptual consequences? Our study shows that walking increased the contrast-dependent influence of peripheral visual input on central visual input. This increase is prevalent in stimulus-locked electroencephalogram (EEG) responses (steady-state visual evoked potential [SSVEP]) alongside perceptual performance. Ongoing alpha oscillations (approximately 10 Hz) further positively correlated with the walking-induced changes of SSVEP amplitude, indicating the involvement of an altered inhibitory process during walking. The results predicted that walking leads to an increased processing of peripheral visual input. A second study indeed showed an increased contrast sensitivity for peripheral compared to central stimuli when subjects were walking. Our work shows complementary neurophysiological and behavioural evidence corroborating animal findings that walking leads to a change in early visual neuronal activity in humans. That neuronal modulation due to walking is indeed linked to specific perceptual changes extends the existing animal work.


Assuntos
Potenciais Evocados Visuais/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Desempenho Psicomotor/fisiologia , Visão Ocular/fisiologia , Caminhada/fisiologia , Adulto , Ritmo alfa/fisiologia , Feminino , Humanos , Locomoção/fisiologia , Masculino , Estimulação Luminosa , Córtex Visual/fisiologia
12.
Behav Processes ; 169: 103980, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31580904

RESUMO

General locomotor activity is a highly variable phenotypic trait of animals. In domestic chickens it is different within and between breeds. The general locomotor activity is a substantially heritable trait and has been shown to be correlated with several other behavioural traits, such as for example feather pecking and anxiety in chickens. However, whether there is a relation between different levels of general locomotor activity and behavioural changes remained unclear. Therefore, a selection line model system has been established, where hens from the same founder population were selected over eight generations for either high or low general locomotor activity. The selection led to significant increases, respectively decreases in general locomotor activity and differences in growth. We here tested 128 hens of the 8th generation in three behavioural tests. We assumed fearfulness to be affected from selection on general locomotor activity, which we tested in a tonic immobility test. Socio-positive and socio-negative behaviours were tested in respective test paradigms. Fearfulness was higher in hens selected for high general locomotor activity. Social behavioural traits and feather pecking were not affected by selection for general locomotor activity. Evolutionary mechanisms that link fear and general locomotor activity are discussed and also why social behaviours and feather pecking seems not to be affected from selection on general locomotor activity. Our results provide interesting new insights on how selection on one trait, general locomotor activity, affects the behavioural phenotype in other dimensions too.


Assuntos
Comportamento Animal/fisiologia , Cruzamento , Locomoção/fisiologia , Comportamento Social , Animais , Galinhas , Feminino , Fenótipo
13.
Nat Commun ; 10(1): 4770, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628317

RESUMO

Animals perform or terminate particular behaviors by integrating external cues and internal states through neural circuits. Identifying neural substrates and their molecular modulators promoting or inhibiting animal behaviors are key steps to understand how neural circuits control behaviors. Here, we identify the Cholecystokinin-like peptide Drosulfakinin (DSK) that functions at single-neuron resolution to suppress male sexual behavior in Drosophila. We found that Dsk neurons physiologically interact with male-specific P1 neurons, part of a command center for male sexual behaviors, and function oppositely to regulate multiple arousal-related behaviors including sex, sleep and spontaneous walking. We further found that the DSK-2 peptide functions through its receptor CCKLR-17D3 to suppress sexual behaviors in flies. Such a neuropeptide circuit largely overlaps with the fruitless-expressing neural circuit that governs most aspects of male sexual behaviors. Thus DSK/CCKLR signaling in the sex circuitry functions antagonistically with P1 neurons to balance arousal levels and modulate sexual behaviors.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Oligopeptídeos/metabolismo , Fatores de Transcrição/metabolismo , Animais , Animais Geneticamente Modificados , Nível de Alerta/fisiologia , Comunicação Celular/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Feminino , Locomoção/fisiologia , Masculino , Proteínas do Tecido Nervoso/genética , Neurônios/citologia , Neuropeptídeos/genética , Oligopeptídeos/genética , Comportamento Sexual Animal/fisiologia , Transdução de Sinais/genética , Sono/fisiologia , Fatores de Transcrição/genética
14.
Nat Commun ; 10(1): 4796, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641138

RESUMO

Interneurons (INs) coordinate motoneuron activity to generate appropriate patterns of muscle contractions, providing animals with the ability to adjust their body posture and to move over a range of speeds. In Drosophila larvae several IN subtypes have been morphologically described and their function well documented. However, the general lack of molecular characterization of those INs prevents the identification of evolutionary counterparts in other animals, limiting our understanding of the principles underlying neuronal circuit organization and function. Here we characterize a restricted subset of neurons in the nerve cord expressing the Maf transcription factor Traffic Jam (TJ). We found that TJ+ neurons are highly diverse and selective activation of these different subtypes disrupts larval body posture and induces specific locomotor behaviors. Finally, we show that a small subset of TJ+ GABAergic INs, singled out by the expression of a unique transcription factors code, controls larval crawling speed.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Interneurônios/fisiologia , Fatores de Transcrição Maf Maior/metabolismo , Atividade Motora/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Animais , Animais Geneticamente Modificados , Drosophila/embriologia , Proteínas de Drosophila/genética , Embrião não Mamífero/fisiologia , Regulação da Expressão Gênica , Inativação Gênica , Larva/fisiologia , Locomoção/fisiologia , Fatores de Transcrição Maf Maior/genética , Proteínas Proto-Oncogênicas/genética , Raízes Nervosas Espinhais/fisiologia , Ácido gama-Aminobutírico/metabolismo
15.
Nat Commun ; 10(1): 4812, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645554

RESUMO

Neuronal networks of the mammalian motor cortex (M1) are important for dexterous control of limb joints. Yet it remains unclear how encoding of joint movement in M1 depends on varying environmental contexts. Using calcium imaging we measured neuronal activity in layer 2/3 of the M1 forelimb region while mice grasped regularly or irregularly spaced ladder rungs during locomotion. We found that population coding of forelimb joint movements is sparse and varies according to the flexibility demanded from individual joints in the regular and irregular context, even for equivalent grasping actions across conditions. This context-dependence of M1 encoding emerged during task learning, fostering higher precision of grasping actions, but broke apart upon silencing of projections from secondary motor cortex (M2). These findings suggest that M1 exploits information from M2 to adapt encoding of joint movements to the flexibility demands of distinct familiar contexts, thereby increasing the accuracy of motor output.


Assuntos
Membro Anterior , Força da Mão , Articulações/fisiologia , Locomoção/fisiologia , Córtex Motor/fisiologia , Neurônios/fisiologia , Animais , Camundongos , Córtex Motor/diagnóstico por imagem , Imagem Óptica , Optogenética , Amplitude de Movimento Articular
16.
Nat Commun ; 10(1): 4095, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506439

RESUMO

Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.


Assuntos
Caenorhabditis elegans/fisiologia , Cálcio/metabolismo , Neurônios GABAérgicos/metabolismo , Locomoção/fisiologia , Neuropeptídeos/metabolismo , Sono/fisiologia , Animais , Axônios/metabolismo , Caenorhabditis elegans/citologia , Neurônios Colinérgicos/fisiologia , Junções Comunicantes/metabolismo , Luz , Modelos Biológicos , Neurônios Motores/fisiologia , Músculos/citologia , Fenótipo , Transdução de Sinais , Ácido gama-Aminobutírico/metabolismo
17.
Nat Commun ; 10(1): 4197, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519892

RESUMO

In all vertebrates, excitatory spinal interneurons execute dynamic adjustments in the timing and amplitude of locomotor movements. Currently, it is unclear whether interneurons responsible for timing control are distinct from those involved in amplitude control. Here, we show that in larval zebrafish, molecularly, morphologically and electrophysiologically distinct types of V2a neurons exhibit complementary patterns of connectivity. Stronger higher-order connections from type I neurons to other excitatory V2a and inhibitory V0d interneurons provide timing control, while stronger last-order connections from type II neurons to motor neurons provide amplitude control. Thus, timing and amplitude are coordinated by distinct interneurons distinguished not by their occupation of hierarchically-arranged anatomical layers, but rather by differences in the reliability and probability of higher-order and last-order connections that ultimately form a single anatomical layer. These findings contribute to our understanding of the origins of timing and amplitude control in the spinal cord.


Assuntos
Interneurônios/metabolismo , Locomoção/fisiologia , Animais , Interneurônios/citologia , Neurônios Motores/citologia , Neurônios Motores/metabolismo , Medula Espinal/citologia , Medula Espinal/metabolismo , Peixe-Zebra
18.
J Neuroinflammation ; 16(1): 173, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470863

RESUMO

BACKGROUND: Disturbances in clock genes affect almost all patients with Alzheimer's disease (AD), as evidenced by their altered sleep/wake cycle, thermoregulation, and exacerbation of cognitive impairment. As microglia-mediated neuroinflammation proved to be a driver of AD rather than a result of the disease, in this study, we evaluated the relationship between clock gene disturbance and neuroinflammation in microglia and their contribution to the onset of AD. METHODS: In this study, the expression of clock genes and inflammatory-related genes was examined in MACS microglia isolated from 2-month-old amyloid precursor protein knock-in (APP-KI) and wild-type (WT) mice using cap analysis gene expression (CAGE) deep sequencing and RT-PCR. The effects of clock gene disturbance on neuroinflammation and relevant memory changes were examined in 2-month-old APP-KI and WT mice after injection with SR9009 (a synthetic agonist for REV-ERB). The microglia morphology was studied by staining, neuroinflammation was examined by Western blotting, and cognitive changes were examined by Y-maze and novel object recognition tests. RESULTS: CLOCK/BMAL1-driven transcriptional negative feedback loops were impaired in the microglia from 2-month-old APP-KI mice. Pro-inflammatory genes in microglia isolated from APP-KI mice were significantly higher than those isolated from WT mice at Zeitgeber time 14. The expression of pro-inflammatory genes was positively associated with NF-κB activation and negatively associated with the BMAL1 expression. SR9009 induced the activation of microglia, the increased expression of pro-inflammatory genes, and cognitive decline in 2-month-old APP-KI mice. CONCLUSION: Clock gene disturbance in microglia is involved in the early onset of AD through the induction of chronic neuroinflammation, which may be a new target for preventing or slowing AD.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Proteínas CLOCK/metabolismo , Técnicas de Introdução de Genes/métodos , Mediadores da Inflamação/metabolismo , Microglia/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/efeitos dos fármacos , Proteínas CLOCK/antagonistas & inibidores , Proteínas CLOCK/genética , Inflamação/genética , Inflamação/metabolismo , Mediadores da Inflamação/agonistas , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Pirrolidinas/toxicidade , Tiofenos/toxicidade
19.
Nat Commun ; 10(1): 3434, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366920

RESUMO

Bacterial contamination of biological channels, catheters or water resources is a major threat to public health, which can be amplified by the ability of bacteria to swim upstream. The mechanisms of this 'rheotaxis', the reorientation with respect to flow gradients, are still poorly understood. Here, we follow individual E. coli bacteria swimming at surfaces under shear flow using 3D Lagrangian tracking and fluorescent flagellar labelling. Three transitions are identified with increasing shear rate: Above a first critical shear rate, bacteria shift to swimming upstream. After a second threshold, we report the discovery of an oscillatory rheotaxis. Beyond a third transition, we further observe coexistence of rheotaxis along the positive and negative vorticity directions. A theoretical analysis explains these rheotaxis regimes and predicts the corresponding critical shear rates. Our results shed light on bacterial transport and reveal strategies for contamination prevention, rheotactic cell sorting, and microswimmer navigation in complex flow environments.


Assuntos
Escherichia coli/fisiologia , Hidrodinâmica , Locomoção/fisiologia , Equipamentos e Provisões/microbiologia , Fluorescência , Modelos Biológicos , Propriedades de Superfície , Movimentos da Água
20.
Nat Commun ; 10(1): 3690, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417086

RESUMO

Associative memory is the main type of learning by which complex organisms endowed with evolved nervous systems respond efficiently to certain environmental stimuli. It has been found in different multicellular species, from cephalopods to humans, but never in individual cells. Here we describe a motility pattern consistent with associative conditioned behavior in the microorganism Amoeba proteus. We use a controlled direct-current electric field as the conditioned stimulus, and a specific chemotactic peptide as the unconditioned stimulus. The amoebae are capable of linking two independent past events, generating persistent locomotion movements that can prevail for 44 min on average. We confirm a similar behavior in a related species, Metamoeba leningradensis. Thus, our results indicate that unicellular organisms can modify their behavior during migration by associative conditioning.


Assuntos
Amoeba/fisiologia , Aprendizagem por Associação/fisiologia , Condicionamento Clássico/fisiologia , Locomoção/fisiologia
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