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1.
Exp Neurol ; 347: 113886, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34624327

RESUMO

Children with low physical activity and interactions with environment experience atypical sensorimotor development and maturation leading to anatomical and functional disorganization of the sensorimotor circuitry and also to enduring altered motor function. Previous data have shown that postnatal movement restriction in rats results in locomotor disturbances, functional disorganization and hyperexcitability of the hind limb representations in the somatosensory and motor cortices, without apparent brain damage. Due to the reciprocal interplay between the nervous system and muscle, it is difficult to determine whether muscle alteration is the cause or the result of the altered sensorimotor behavior (Canu et al., 2019). In the present paper, our objectives were to evaluate the impact of early movement restriction leading to sensorimotor restriction (SMR) during development on the postural soleus muscle and on sensorimotor performance in rats, and to determine whether changes were reversed when typical activity was resumed. Rats were submitted to SMR by hind limb immobilization for 16 h / day from birth to postnatal day 28 (PND28). In situ isometric contractile properties of soleus muscle, fiber cross sectional area (CSA) and myosin heavy chain content (MHC) were studied at PND28 and PND60. In addition, the motor function was evaluated weekly from PND28 to PND60. At PND28, SMR rats presented a severe atrophy of soleus muscle, a decrease in CSA and a force loss. The muscle maturation appeared delayed, with persistence of neonatal forms of MHC. Changes in kinetic properties were moderate or absent. The Hoffmann reflex provided evidence for spinal hyperreflexia and signs of spasticity. Most changes were reversed at PND60, except muscle atrophy. Functional motor tests that require a good limb coordination, i.e. rotarod and locomotion, showed an enduring alteration related to SMR, even after one month of 'typical' activity. On the other hand, paw withdrawal test and grip test were poorly affected by SMR whereas spontaneous locomotor activity increased over time. Our results support the idea that proprioceptive feedback is at least as important as the amount of motor activity to promote a typical development of motor function. A better knowledge of the interplay between hypoactivity, muscle properties and central motor commands may offer therapeutic perspectives for children suffering from neurodevelopmental disorders.


Assuntos
Retroalimentação Sensorial/fisiologia , Elevação dos Membros Posteriores/efeitos adversos , Atividade Motora/fisiologia , Músculo Esquelético/fisiopatologia , Animais , Feminino , Masculino , Movimento/fisiologia , Atrofia Muscular/patologia , Ratos , Ratos Sprague-Dawley
2.
Cell Mol Life Sci ; 79(1): 7, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936028

RESUMO

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons and severe muscle atrophy without effective treatment. Most research on the disease has been focused on studying motor neurons and supporting cells of the central nervous system. Strikingly, the recent observations have suggested that morpho-functional alterations in skeletal muscle precede motor neuron degeneration, bolstering the interest in studying muscle tissue as a potential target for the delivery of therapies. We previously showed that the systemic administration of the P2XR7 agonist, 2'(3')-O-(4-benzoylbenzoyl) adenosine 5-triphosphate (BzATP), enhanced the metabolism and promoted the myogenesis of new fibres in the skeletal muscles of SOD1G93A mice. Here we further corroborated this evidence showing that intramuscular administration of BzATP improved the motor performance of ALS mice by enhancing satellite cells and the muscle pro-regenerative activity of infiltrating macrophages. The preservation of the skeletal muscle retrogradely propagated along with the motor unit, suggesting that backward signalling from the muscle could impinge on motor neuron death. In addition to providing the basis for a suitable adjunct multisystem therapeutic approach in ALS, these data point out that the muscle should be at the centre of ALS research as a target tissue to address novel therapies in combination with those oriented to the CNS.


Assuntos
Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/fisiopatologia , Atividade Motora/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/administração & dosagem , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Axônios/patologia , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Denervação , Modelos Animais de Doenças , Progressão da Doença , Feminino , Membro Posterior/patologia , Humanos , Inflamação/patologia , Injeções Intramusculares , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Transgênicos , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/inervação , Atrofia Muscular/patologia , Fenótipo , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Células Satélites de Músculo Esquelético/patologia , Células de Schwann/patologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia
3.
PLoS One ; 16(10): e0258322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34624051

RESUMO

The blink rate increases if a person indulges in a conversation compared to quiet rest. Since various factors were suggested to explain this increase, the present series of studies tested the influence of different motor activities, cognitive processes and auditory input on the blink behavior but at the same time minimized visual stimulation as well as social influences. Our results suggest that neither cognitive demands without verbalization, nor isolated lip, jaw or tongue movements, nor auditory input during vocalization or listening influence our blinking behavior. In three experiments, we provide evidence that complex facial movements during unvoiced speaking are the driving factors that increase blinking. If the complexity of the motor output increased such as during the verbalization of speech, the blink rate rose even more. Similarly, complex facial movements without cognitive demands, such as sucking on a lollipop, increased the blink rate. Such purely motor-related influences on blinking advise caution particularly when using blink rates assessed during patient interviews as a neurological indicator.


Assuntos
Piscadela/fisiologia , Atividade Motora/fisiologia , Fala/fisiologia , Adulto , Percepção Auditiva/fisiologia , Cognição/fisiologia , Feminino , Humanos , Masculino , Análise e Desempenho de Tarefas , Adulto Jovem
4.
PLoS One ; 16(10): e0258305, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648537

RESUMO

Increasing the amount of regular physical education lessons in school is currently discussed in many countries in order to increase physical activity in youth. The purpose of this study was to compare the motor performance of pupils from an observation group participating in a school trial of two additional physical education lessons (5 lessons of each 50 min/week) without a specific intervention program to a control group with a regular amount of three physical education lessons (3 lessons of each 50 min/week) as indicated by the standard Austrian school curriculum. In this cohort study motor performance of 140 adolescents (12.7±0.5 years) was assessed by means of the German Motor Performance Test 6-18 over a period of 1.5 years with measurement time points before (T1), after eight months (T2) and at the end of the observation period (T3). Two- and three-way mixed analysis of variance were used to detect time, group and interaction effects. Although the observation group demonstrated a higher total motor performance score at all time points (P = 0.005), the improvement over time in total motor performance (P < 0.001) was more pronounced in the control group. Girls and boys developed differently over time (time*gender interaction: P = 0.001), whereby group allocation did not affect this interaction (time*gender*group: P = 0.167). Anyway, girls of control group tend to benefit most of additional physical education lessons. Sports club members scored significantly higher in motor performance across the observation period (P = 0.018) irrespective of group allocation. These findings indicate that there could be a ceiling effect in what the pupils could achieve in terms of motor performance as the pupils of the observation group might have reached this point earlier than their counterparts in the control group. Nevertheless, sports club membership seems to reveal some benefits. Whether improving quality and specificity of the single physical lessons might be superior to merely adding additional ones needs to be confirmed in future studies.


Assuntos
Atividade Motora/fisiologia , Educação Física e Treinamento , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Esportes
5.
Int J Mol Sci ; 22(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34502541

RESUMO

Inhibitor of DNA binding (Id) genes comprise a family of four helix-loop-helix (HLH) transcriptional inhibitors. Our earlier studies revealed a role for ID2 within the circadian system, contributing to input, output, and core clock function through its interaction with CLOCK and BMAL1. Here, we explore the contribution of ID4 to the circadian system using a targeted disruption of the Id4 gene. Attributes of the circadian clock were assessed by monitoring the locomotor activity of Id4-/- mice, and they revealed disturbances in its operation. Id4-mutant mice expressed a shorter circadian period length, attenuated phase shifts in responses to continuous and discrete photic cues, and an advanced phase angle of entrainment under a 12:12 light:dark cycle and under short and long photoperiods. To understand the basis for these properties, suprachiasmatic nucleus (SCN) and retinal structures were examined. Anatomical analysis reveals a smaller Id4-/- SCN in the width dimension, which is a finding consistent with its smaller brain. As a result of this feature, anterograde tracing in Id4-/- mice revealed retinal afferents innovate a disproportionally larger SCN area. The Id4-/- photic entrainment responses are unlikely to be due to an impaired function of the retinal pathways since Id4-/- retinal anatomy and function tested by pupillometry were similar to wild-type mice. Furthermore, these circadian characteristics are opposite to those exhibited by the Id2-/- mouse, suggesting an opposing influence of the ID4 protein within the circadian system; or, the absence of ID4 results in changes in the expression or activity of other members of the Id gene family. Expression analysis of the Id genes within the Id4-/- SCN revealed a time-of-day specific elevated Id1. It is plausible that the increased Id1 and/or absence of ID4 result in changes in interactions with bHLH canonical clock components or with targets upstream and/or downstream of the clock, thereby resulting in abnormal properties of the circadian clock and its entrainment.


Assuntos
Relógios Circadianos/genética , Proteínas Inibidoras de Diferenciação/genética , Proteínas Circadianas Period/genética , Fotoperíodo , Retina/metabolismo , Núcleo Supraquiasmático/metabolismo , Animais , Ritmo Circadiano , Expressão Gênica , Proteínas Inibidoras de Diferenciação/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética , Atividade Motora/fisiologia , Proteínas Circadianas Period/metabolismo , Retina/anatomia & histologia , Núcleo Supraquiasmático/anatomia & histologia
6.
PLoS One ; 16(9): e0255892, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34525103

RESUMO

Describing the maturation of information processing in children is fundamental for developmental science. Although non-linear changes in reaction times have been well-documented, direct measurement of the development of the different processing components is lacking. In this study, electromyography was used to quantify the maturation of premotor and motor processes on a sample of 114 children (6-14 years-old) and 15 adults. Using a model-based approach, we show that the development of these two components is well-described by an exponential decrease in duration, with the decay rate being equal for the two components. These findings provide the first unbiased evidence in favour of the common developmental rate of nonmotor and motor processes by directly confronting rates of development of different processing components within the same task. This common developmental rate contrasts with the differential physical maturation of region-specific cerebral gray and white matter. Tentative paths of interpretation are proposed in the discussion.


Assuntos
Desenvolvimento Infantil , Substância Cinzenta/fisiologia , Atividade Motora/fisiologia , Tempo de Reação/fisiologia , Substância Branca/fisiologia , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino
7.
Elife ; 102021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34517941

RESUMO

Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA-binding protein that regulates translation and is required for mammalian development. Here, we show that depletion of Drosophila CNBP in muscles causes ageing-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscles from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions.


Assuntos
Proteínas de Drosophila/metabolismo , Atividade Motora/genética , Atividade Motora/fisiologia , Poliaminas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Animais Geneticamente Modificados , Linhagem Celular , Regulação para Baixo/fisiologia , Proteínas de Drosophila/genética , Drosophila melanogaster , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Músculo Esquelético/metabolismo , Distrofia Miotônica/genética , Distrofia Miotônica/metabolismo , Biossíntese de Proteínas , Putrescina/farmacologia , Interferência de RNA , Proteínas de Ligação a RNA/genética , Espermidina/farmacologia
8.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34544853

RESUMO

Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at ≤30 d (acute), 2 to 3 mo (subacute), or ≥6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 ± 2.63, P = 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 ± 2.59 points, P = 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 ± 2.25, P = 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans.


Assuntos
Atividade Motora/fisiologia , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/terapia , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
9.
Biochem Biophys Res Commun ; 577: 64-70, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34507067

RESUMO

To detect a small amount of Period1 (Per1) expression, we developed a micro-photomultiplier tube (µPMT) system which can be used both in vivo and in vitro. Using this system, we succeeded in detecting Per1 gene expression in the skin of freely moving mice over 240 times higher compared with that of the tissue contact optical sensor (TCS) as previously reported. For in vitro studies, we succeeded in detecting elevated Per1 expression by streptozotocin (STZ) treatment in the scalp hairs at an early stage of diabetes, when glucose content in the blood was still normal. In addition, we could detect elevated Per1 expression in a single whisker hair at the time of diabetes onset. These results show that our µPMT system responds to minute changes in gene expression in freely moving mice in vivo and in mice hair follicles in vitro. Furthermore, Per1 in the hair can be used for a marker of diabetic aggravation.


Assuntos
Expressão Gênica , Luciferases/genética , Medições Luminescentes/métodos , Proteínas Circadianas Period/genética , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Cabelo/metabolismo , Luciferases/metabolismo , Medições Luminescentes/instrumentação , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atividade Motora/fisiologia , Movimento/fisiologia , Proteínas Circadianas Period/metabolismo , Reprodutibilidade dos Testes , Couro Cabeludo/metabolismo , Pele/citologia , Pele/metabolismo , Vibrissas/metabolismo
10.
Elife ; 102021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473059

RESUMO

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of firing patterns and phase relationships helped to identify possible mechanisms underlying the locomotor movements of developing zebrafish. Notably, our simulations demonstrated how the site and the operation of rhythm generation could transition between coiling and swimming. The simulations also underlined the importance of contralateral excitation to multiple tail beats. They allowed us to estimate the sensitivity of spinal locomotor networks to motor command amplitude, synaptic weights, length of ascending and descending axons, and firing behavior. These models will serve as valuable tools to test and further understand the operation of spinal circuits for locomotion.


Assuntos
Locomoção/fisiologia , Modelos Biológicos , Rede Nervosa/fisiologia , Medula Espinal/fisiologia , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/fisiologia , Animais , Atividade Motora/fisiologia , Neurônios Motores/fisiologia , Neurônios/fisiologia , Natação/fisiologia
11.
Sci Rep ; 11(1): 16943, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417496

RESUMO

It is a widely held assumption that the brain performs perceptual inference by combining sensory information with prior expectations, weighted by their uncertainty. A distinction can be made between higher- and lower-level priors, which can be manipulated with associative learning and sensory priming, respectively. Here, we simultaneously investigate priming and the differential effect of auditory vs. visual associative cues on visual perception, and we also examine the reliability of individual differences. Healthy individuals (N = 29) performed a perceptual inference task twice with a one-week delay. They reported the perceived direction of motion of dot pairs, which were preceded by a probabilistic visuo-acoustic cue. In 30% of the trials, motion direction was ambiguous, and in half of these trials, the auditory versus the visual cue predicted opposing directions. Cue-stimulus contingency could change every 40 trials. On ambiguous trials where the visual and the auditory cue predicted conflicting directions of motion, participants made more decisions consistent with the prediction of the acoustic cue. Increased predictive processing under stimulus uncertainty was indicated by slower responses to ambiguous (vs. non-ambiguous) stimuli. Furthermore, priming effects were also observed in that perception of ambiguous stimuli was influenced by perceptual decisions on the previous ambiguous and unambiguous trials as well. Critically, behavioural effects had substantial inter-individual variability which showed high test-retest reliability (intraclass correlation coefficient (ICC) > 0.78). Overall, higher-level priors based on auditory (vs. visual) information had greater influence on visual perception, and lower-level priors were also in action. Importantly, we observed large and stable differences in various aspects of task performance. Computational modelling combined with neuroimaging could allow testing hypotheses regarding the potential mechanisms causing these behavioral effects. The reliability of the behavioural differences implicates that such perceptual inference tasks could be valuable tools during large-scale biomarker and neuroimaging studies.


Assuntos
Percepção Auditiva/fisiologia , Individualidade , Estimulação Luminosa , Percepção Visual/fisiologia , Adulto , Sinais (Psicologia) , Feminino , Humanos , Masculino , Atividade Motora/fisiologia , Reprodutibilidade dos Testes , Transtorno da Personalidade Esquizotípica/fisiopatologia , Análise e Desempenho de Tarefas
12.
BMJ ; 374: n1743, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348957

RESUMO

OBJECTIVES: To examine multiple objective and self-reported measures of motor function for their associations with mortality. DESIGN: Prospective cohort study. SETTING: UK based Whitehall II cohort study, which recruited participants aged 35-55 years in 1985-88; motor function component was added at the 2007-09 wave. PARTICIPANTS: 6194 participants with motor function measures in 2007-09 (mean age 65.6, SD 5.9), 2012-13, and 2015-16. MAIN OUTCOME MEASURES: All cause mortality between 2007 and 2019 in relation to objective measures (walking speed, grip strength, and timed chair rises) and self-reported measures (physical component summary score of the SF-36 and limitations in basic and instrumental activities of daily living (ADL)) of motor function. RESULTS: One sex specific standard deviation poorer motor function in 2007-09 (cases/total, 610/5645) was associated with an increased mortality risk of 22% (95% confidence interval 12% to 33%) for walking speed, 15% (6% to 25%) for grip strength, 14% (7% to 23%) for timed chair rises, and 17% (8% to 26%) for physical component summary score over a mean 10.6 year follow-up. Having basic/instrumental ADL limitations was associated with a 30% (7% to 58%) increased mortality risk. These associations were progressively stronger when measures were drawn from 2012-13 (mean follow-up 6.8 years) and 2015-16 (mean follow-up 3.7 years). Analysis of trajectories showed poorer motor function in decedents (n=484) than survivors (n=6194) up to 10 years before death for timed chair rises (standardised difference 0.35, 95% confidence interval 0.12 to 0.59; equivalent to a 1.2 (men) and 1.3 (women) second difference), nine years for walking speed (0.21, 0.05 to 0.36; 5.5 (men) and 5.3 (women) cm/s difference), six years for grip strength (0.10, 0.01 to 0.20; 0.9 (men) and 0.6 (women) kg difference), seven years for physical component summary score (0.15, 0.05 to 0.25; 1.2 (men) and 1.6 (women) score difference), and four years for basic/instrumental ADL limitations (prevalence difference 2%, 0% to 4%). These differences increased in the period leading to death for timed chair rises, physical component summary score, and ADL limitations. CONCLUSION: Motor function in early old age has a robust association with mortality, with evidence of terminal decline emerging early in measures of overall motor function (timed chair rises and physical component summary score) and late in basic/instrumental ADL limitations.


Assuntos
Força da Mão/fisiologia , Atividade Motora/fisiologia , Desempenho Psicomotor/fisiologia , Velocidade de Caminhada/fisiologia , Atividades Cotidianas , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Taxa de Sobrevida , Fatores de Tempo , Reino Unido
13.
J Neurosci ; 41(41): 8589-8602, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34429377

RESUMO

The effective development of novel therapies in mouse models of neurologic disorders relies on behavioral assessments that provide accurate read-outs of neuronal dysfunction and/or degeneration. We designed an automated behavioral testing system (PiPaw), which integrates an operant lever-pulling task directly into the mouse home cage. This task is accessible to group-housed mice 24 h per day, enabling high-throughput longitudinal analysis of forelimb motor learning. Moreover, this design eliminates the need for exposure to novel environments and minimizes experimenter interaction, significantly reducing two of the largest stressors associated with animal behavior. Male mice improved their performance of this task over 1 week of testing by reducing intertrial variability of reward-related kinematic parameters (pull amplitude or peak velocity). In addition, mice displayed short-term improvements in reward rate, and a concomitant decrease in movement variability, over the course of brief bouts of task engagement. We used this system to assess motor learning in mouse models of the inherited neurodegenerative disorder, Huntington disease (HD). Despite having no baseline differences in task performance, male Q175-FDN HD mice were unable to modulate the variability of their movements to increase reward on either short or long timescales. Task training was associated with a decrease in the amplitude of spontaneous excitatory activity recorded from striatal medium spiny neurons in the hemisphere contralateral to the trained forelimb in WT mice; however, no such changes were observed in Q175-FDN mice. This behavioral screening platform should prove useful for preclinical drug trials toward improved treatments in HD and other neurologic disorders.SIGNIFICANCE STATEMENT In order to develop effective therapies for neurologic disorders, such as Huntington disease (HD), it is important to be able to accurately and reliably assess the behavior of mouse models of these conditions. Moreover, these behavioral assessments should provide an accurate readout of underlying neuronal dysfunction and/or degeneration. In this paper, we used an automated behavioral testing system to assess motor learning in mice within their home cage. Using this system, we were able to study motor abnormalities in HD mice with an unprecedented level of detail, and identified a specific behavioral deficit associated with an underlying impairment in striatal neuronal plasticity. These results validate the usefulness of this system for assessing behavior in mouse models of HD and other neurologic disorders.


Assuntos
Fenômenos Biomecânicos/fisiologia , Condicionamento Operante/fisiologia , Doença de Huntington/genética , Doença de Huntington/fisiopatologia , Atividade Motora/fisiologia , Recompensa , Animais , Ingestão de Líquidos/fisiologia , Membro Anterior/fisiopatologia , Técnicas de Introdução de Genes , Masculino , Camundongos , Camundongos Transgênicos
14.
PLoS One ; 16(7): e0254361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242360

RESUMO

An Event Related Potential (ERP) component called the Sustained Posterior Negativity (SPN) is generated by regular visual patterns (e.g. vertical reflectional symmetry, horizontal reflectional symmetry or rotational symmetry). Behavioural studies suggest symmetry becomes increasingly salient when the exemplars update rapidly. In line with this, Experiment 1 (N = 48) found that SPN amplitude increased when three different reflectional symmetry patterns were presented sequentially. We call this effect 'SPN priming'. We then exploited SPN priming to investigate independence of different symmetry representations. SPN priming did not survive changes in retinal location (Experiment 2, N = 48) or non-orthogonal changes in axis orientation (Experiment 3, N = 48). However, SPN priming transferred between vertical and horizontal axis orientations (Experiment 4, N = 48) and between reflectional and rotational symmetry (Experiment 5, N = 48). SPN priming is interesting in itself, and a useful new method for identifying functional boundaries of the symmetry response. We conclude that visual regularities at different retinal locations are coded independently. However, there is some overlap between different regularities presented at the same retinal location.


Assuntos
Potenciais Evocados/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Córtex Visual/fisiologia , Adolescente , Adulto , Eletroencefalografia , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Adulto Jovem
15.
Elife ; 102021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34323218

RESUMO

We investigated the neural representation of locomotion in the nematode C. elegans by recording population calcium activity during movement. We report that population activity more accurately decodes locomotion than any single neuron. Relevant signals are distributed across neurons with diverse tunings to locomotion. Two largely distinct subpopulations are informative for decoding velocity and curvature, and different neurons' activities contribute features relevant for different aspects of a behavior or different instances of a behavioral motif. To validate our measurements, we labeled neurons AVAL and AVAR and found that their activity exhibited expected transients during backward locomotion. Finally, we compared population activity during movement and immobilization. Immobilization alters the correlation structure of neural activity and its dynamics. Some neurons positively correlated with AVA during movement become negatively correlated during immobilization and vice versa. This work provides needed experimental measurements that inform and constrain ongoing efforts to understand population dynamics underlying locomotion in C. elegans.


Assuntos
Encéfalo/citologia , Atividade Motora/fisiologia , Neurônios/fisiologia , Animais , Encéfalo/fisiologia , Caenorhabditis elegans
16.
Sci Rep ; 11(1): 15386, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321561

RESUMO

Sleep problems and regular leisure time physical activity (LTPA) are interrelated and have contrasting effects on risk of back pain. However, no studies have investigated the influence of long-term poor sleep quality on risk of back-related disability, or if LTPA modifies this association. The study comprised data on 8601 people who participated in three consecutive surveys over ~ 22 years, and who reported no chronic back pain at the two first surveys. Adjusted risk ratios (RRs) for back-related disability were calculated at the last survey, associated with the joint effect of changes in sleep quality between the two first surveys and meeting physical activity guidelines at the second survey. Compared to people with long-term good sleep, people with long-term poor sleep had nearly twice the risk of back-related disability (RR 1.92, 95% CI 1.48-2.49). There was no statistical interaction between sleep and LTPA but people who reported long-term poor sleep and meeting the physical activity guidelines had 35% lower risk of back-related disability compared to people with same level of sleep problems, but who not met the guidelines. These findings suggest that long-term poor sleep quality contributes to a substantially increased risk of chronic and disabling back pain irrespective of LTPA.


Assuntos
Dor Crônica/terapia , Dor Lombar/terapia , Distúrbios do Início e da Manutenção do Sono/terapia , Sono/fisiologia , Adulto , Dor Crônica/complicações , Dor Crônica/fisiopatologia , Exercício Físico , Feminino , Humanos , Atividades de Lazer , Dor Lombar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/fisiopatologia
17.
J Clin Invest ; 131(18)2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264865

RESUMO

BACKGROUNDCertain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude), and shift work (irregularity) are associated with increased risk for drug use. Dopaminergic (DA) signaling has been hypothesized to mediate the associations, though clinical evidence is lacking.METHODSWe examined associations between rhythm components and striatal D1 (D1R) and D2/3 receptor (D2/3R) availability in 32 healthy adults (12 female, 20 male; age 42.40 ± 12.22 years) and its relationship to drug reward. Rest-activity rhythms were assessed by 1-week actigraphy combined with self-reports. [11C]NNC112 and [11C]raclopride positron emission tomography (PET) scans were conducted to measure D1R and D2/3R availability, respectively. Additionally, self-reported drug-rewarding effects of 60 mg oral methylphenidate were assessed.RESULTSWe found that delayed rhythm was associated with higher D1R availability in caudate, which was not attributable to sleep loss or so-called social jet lag, whereas physical inactivity was associated with higher D2/3R availability in nucleus accumbens (NAc). Delayed rest-activity rhythm, higher caudate D1R, and NAc D2/3R availability were associated with greater sensitivity to the rewarding effects of methylphenidate.CONCLUSIONThese findings reveal specific components of rest-activity rhythms associated with striatal D1R, D2/3R availability, and drug-rewarding effects. Personalized interventions that target rest-activity rhythms may help prevent and treat substance use disorders.TRIAL REGISTRATIONClinicalTrials.gov: NCT03190954.FUNDINGNational Institute on Alcohol Abuse and Alcoholism (ZIAAA000550).


Assuntos
Ritmo Circadiano/fisiologia , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Recompensa , Transtornos Relacionados ao Uso de Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Actigrafia , Adulto , Estimulantes do Sistema Nervoso Central/administração & dosagem , Corpo Estriado/fisiologia , Feminino , Humanos , Masculino , Metilfenidato/administração & dosagem , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Tomografia por Emissão de Pósitrons , Descanso/fisiologia , Adulto Jovem
18.
Commun Biol ; 4(1): 863, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267313

RESUMO

Organisms comprise multiple interacting parts, but few quantitative studies have analysed multi-element systems, limiting understanding of phenotypic evolution. We investigate how disparity of vertebral morphology varies along the axial column of mammalian carnivores - a chain of 27 subunits - and the extent to which morphological variation have been structured by evolutionary constraints and locomotory adaptation. We find that lumbars and posterior thoracics exhibit high individual disparity but low serial differentiation. They are pervasively recruited into locomotory functions and exhibit relaxed evolutionary constraint. More anterior vertebrae also show signals of locomotory adaptation, but nevertheless have low individual disparity and constrained patterns of evolution, characterised by low-dimensional shape changes. Our findings demonstrate the importance of the thoracolumbar region as an innovation enabling evolutionary versatility of mammalian locomotion. Moreover, they underscore the complexity of phenotypic macroevolution of multi-element systems and that the strength of ecomorphological signal does not have a predictable influence on macroevolutionary outcomes.


Assuntos
Adaptação Fisiológica/fisiologia , Evolução Biológica , Carnivoridade/fisiologia , Locomoção/fisiologia , Mamíferos/fisiologia , Coluna Vertebral/fisiologia , Análise de Variância , Animais , Atividade Motora/fisiologia , Coluna Vertebral/anatomia & histologia , Coluna Vertebral/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Microtomografia por Raio-X
19.
J Neurosci ; 41(33): 7086-7102, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34261700

RESUMO

The G-protein-gated inwardly rectifying potassium (Kir3/GIRK) channel is the effector of many G-protein-coupled receptors (GPCRs). Its dysfunction has been linked to the pathophysiology of Down syndrome, Alzheimer's and Parkinson's diseases, psychiatric disorders, epilepsy, drug addiction, or alcoholism. In the hippocampus, GIRK channels decrease excitability of the cells and contribute to resting membrane potential and inhibitory neurotransmission. Here, to elucidate the role of GIRK channels activity in the maintenance of hippocampal-dependent cognitive functions, their involvement in controlling neuronal excitability at different levels of complexity was examined in C57BL/6 male mice. For that purpose, GIRK activity in the dorsal hippocampus CA3-CA1 synapse was pharmacologically modulated by two drugs: ML297, a GIRK channel opener, and Tertiapin-Q (TQ), a GIRK channel blocker. Ex vivo, using dorsal hippocampal slices, we studied the effect of pharmacological GIRK modulation on synaptic plasticity processes induced in CA1 by Schaffer collateral stimulation. In vivo, we performed acute intracerebroventricular (i.c.v.) injections of the two GIRK modulators to study their contribution to electrophysiological properties and synaptic plasticity of dorsal hippocampal CA3-CA1 synapse, and to learning and memory capabilities during hippocampal-dependent tasks. We found that pharmacological disruption of GIRK channel activity by i.c.v. injections, causing either function gain or function loss, induced learning and memory deficits by a mechanism involving neural excitability impairments and alterations in the induction and maintenance of long-term synaptic plasticity processes. These results support the contention that an accurate control of GIRK activity must take place in the hippocampus to sustain cognitive functions.SIGNIFICANCE STATEMENT Cognitive processes of learning and memory that rely on hippocampal synaptic plasticity processes are critically ruled by a finely tuned neural excitability. G-protein-gated inwardly rectifying K+ (GIRK) channels play a key role in maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Here, we demonstrate that modulation of GIRK channels activity, causing either function gain or function loss, transforms high-frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD), inducing deficits in hippocampal-dependent learning and memory. Together, our data show a crucial GIRK-activity-mediated mechanism that governs synaptic plasticity direction and modulates subsequent hippocampal-dependent cognitive functions.


Assuntos
Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/fisiologia , Hipocampo/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Condicionamento Operante/fisiologia , Emoções/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Aprendizagem/fisiologia , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/fisiologia , Desempenho Psicomotor/fisiologia
20.
Sci Rep ; 11(1): 13907, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230552

RESUMO

Successful adaptation to wearing dentures with palatal coverage may be associated with cortical activity changes related to tongue motor control. The purpose was to investigate the brain activity changes during tongue movement in response to a new oral environment. Twenty-eight fully dentate subjects (mean age: 28.6-years-old) who had no experience with removable dentures wore experimental palatal plates for 7 days. We measured tongue motor dexterity, difficulty with tongue movement, and brain activity using functional magnetic resonance imaging during tongue movement at pre-insertion (Day 0), as well as immediately (Day 1), 3 days (Day 3), and 7 days (Day 7) post-insertion. Difficulty with tongue movement was significantly higher on Day 1 than on Days 0, 3, and 7. In the subtraction analysis of brain activity across each day, activations in the angular gyrus and right precuneus on Day 1 were significantly higher than on Day 7. Tongue motor impairment induced activation of the angular gyrus, which was associated with monitoring of the tongue's spatial information, as well as the activation of the precuneus, which was associated with constructing the tongue motor imagery. As the tongue regained the smoothness in its motor functions, the activation of the angular gyrus and precuneus decreased.


Assuntos
Adaptação Fisiológica , Encéfalo/fisiologia , Imageamento por Ressonância Magnética , Movimento/fisiologia , Palato/fisiologia , Língua/fisiologia , Adulto , Mapeamento Encefálico , Feminino , Humanos , Masculino , Atividade Motora/fisiologia
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