Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 18.042
Filtrar
1.
J Neural Eng ; 20(1)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36595241

RESUMO

Objective.Spinal cord neuromodulation has gained much attention for demonstrating improved motor recovery in people with spinal cord injury, motivating the development of clinically applicable technologies. Among them, transcutaneous spinal cord stimulation (tSCS) is attractive because of its non-invasive profile. Many tSCS studies employ a high-frequency (10 kHz) carrier, which has been reported to reduce stimulation discomfort. However, these claims have come under scrutiny in recent years. The purpose of this study was to determine whether using a high-frequency carrier for tSCS is more comfortable at therapeutic amplitudes, which evoke posterior root-muscle (PRM) reflexes.Approach.In 16 neurologically intact participants, tSCS was delivered using a 1 ms long monophasic pulse with and without a high-frequency carrier. Stimulation amplitude and pulse duration were varied and PRM reflexes were recorded from the soleus, gastrocnemius, and tibialis anterior muscles. Participants rated their discomfort during stimulation from 0 to 10 at PRM reflex threshold.Main Results.At PRM reflex threshold, the addition of a high-frequency carrier (0.87 ± 0.2) was equally comfortable as conventional stimulation (1.03 ± 0.18) but required approximately double the charge to evoke the PRM reflex (conventional: 32.4 ± 9.2µC; high-frequency carrier: 62.5 ± 11.1µC). Strength-duration curves for tSCS with a high-frequency carrier had a rheobase that was 4.8× greater and a chronaxie that was 5.7× narrower than the conventional monophasic pulse, indicating that the addition of a high-frequency carrier makes stimulation less efficient in recruiting neural activity in spinal roots.Significance.Using a high-frequency carrier for tSCS is equally as comfortable and less efficient as conventional stimulation at amplitudes required to stimulate spinal dorsal roots.


Assuntos
Traumatismos da Medula Espinal , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/métodos , Medula Espinal/fisiologia , Raízes Nervosas Espinhais/fisiologia , Músculo Esquelético/fisiologia
2.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674942

RESUMO

Sexual dysfunction can be caused by impaired neurotransmission from the peripheral to the central nervous system. Therefore, it is important to evaluate the input of sensory information from the peripheral genital area and investigate the control mechanisms in the spinal cord to clarify the pathological basis of sensory abnormalities in the genital area. However, an in vivo evaluation system for the spinal cord-penile neurotransmission mechanism has not yet been developed. Here, urethane-anesthetized rats were used to evaluate neuronal firing induced by innocuous or nociceptive stimulation of the penis using extracellular recording or patch-clamp techniques in the lumbosacral spinal dorsal horn and electrophysiological evaluation in the peripheral pelvic nerves. As a result, innocuous and nociceptive stimuli-evoked neuronal firing was successfully recorded in the deep and superficial spinal dorsal horns, respectively. The innocuous stimuli-evoked nerve firing was also recorded in the pelvic nerve. These firings were suppressed by lidocaine. To the best of our knowledge, this is the first report of a successful quantitative evaluation of penile stimuli-evoked neuronal firing. This method is not only useful for analyzing the pathological basis of spinal cord-penile neurotransmission in sexual dysfunction but also provides a useful evaluation system in the search for new treatments.


Assuntos
Medula Espinal , Transmissão Sináptica , Masculino , Ratos , Animais , Medula Espinal/fisiologia , Transmissão Sináptica/fisiologia , Corno Dorsal da Medula Espinal , Neurônios , Lidocaína , Pênis
3.
Neuron ; 111(1): 8-9, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36603551

RESUMO

Spinal cord circuits that process cold inputs from the periphery are poorly understood. In this issue of Neuron, Albisetti et al.1 identify a subset of inhibitory interneurons essential to this function.


Assuntos
Interneurônios , Medula Espinal , Medula Espinal/fisiologia , Interneurônios/fisiologia
4.
J Neurosci ; 43(3): 419-432, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36639888

RESUMO

We tested the hypothesis that dorsal cervical epidural electrical stimulation (CEES) increases respiratory activity in male and female anesthetized rats. Respiratory frequency and minute ventilation were significantly increased when CEES was applied dorsally to the C2-C6 region of the cervical spinal cord. By injecting pseudorabies virus into the diaphragm and using c-Fos activity to identify neurons activated during CEES, we found neurons in the dorsal horn of the cervical spinal cord in which c-Fos and pseudorabies were co-localized, and these neurons expressed somatostatin (SST). Using dual viral infection to express the inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD), hM4D(Gi), selectively in SST-positive cells, we inhibited SST-expressing neurons by administering Clozapine N-oxide (CNO). During CNO-mediated inhibition of SST-expressing cervical spinal neurons, the respiratory excitation elicited by CEES was diminished. Thus, dorsal cervical epidural stimulation activated SST-expressing neurons in the cervical spinal cord, likely interneurons, that communicated with the respiratory pattern generating network to effect changes in ventilation.SIGNIFICANCE STATEMENT A network of pontomedullary neurons within the brainstem generates respiratory behaviors that are susceptible to modulation by a variety of inputs; spinal sensory and motor circuits modulate and adapt this output to meet the demands placed on the respiratory system. We explored dorsal cervical epidural electrical stimulation (CEES) excitation of spinal circuits to increase ventilation in rats. We identified dorsal somatostatin (SST)-expressing neurons in the cervical spinal cord that were activated (c-Fos-positive) by CEES. CEES no longer stimulated ventilation during inhibition of SST-expressing spinal neuronal activity, thereby demonstrating that spinal SST neurons participate in the activation of respiratory circuits affected by CEES. This work establishes a mechanistic foundation to repurpose a clinically accessible neuromodulatory therapy to activate respiratory circuits and stimulate ventilation.


Assuntos
Medula Cervical , Ratos , Masculino , Feminino , Animais , Neurônios/fisiologia , Medula Espinal/fisiologia , Somatostatina , Proteínas Proto-Oncogênicas c-fos , Estimulação Elétrica
5.
Med Biol Eng Comput ; 61(2): 555-566, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36538267

RESUMO

Herein, we employed a central pattern generator (CPG), a spinal cord neural network that regulates lower-limb gait during intra-spinal micro-stimulation (ISMS). Particularly, ISMS was used to determine the spatial distribution pattern of CPG sites in the spinal cord and the signal regulation pattern that induced the CPG network to produce coordinated actions. Based on the oscillation phenomenon of the single CPG neurons of Van der Pol (VDP) oscillators, a double-cell CPG neural network model was constructed to realise double lower limbs, six-joint modelling, the simulation of 12 neural circuits, the CPG loci characterising stimuli-inducing alternating movements and changes in polarity stimulation signals in rat hindlimbs, and leg-state change movements. The feasibility and effectiveness of the CPG neural network were verified by recording the electromyographic burst-release mode of the flexor and extensor muscles of the knee joints during CPG electrical stimulation. The results revealed that the output pattern of the CPG presented stable rhythm and coordination characteristics. The 12-neuron CPG model based on the improved VDP equation realised single-point control while significantly reducing the number of stimulation electrodes in the gait training of spinal cord injury patients. We believe that this study advances motor function recovery in rehabilitation medicine.


Assuntos
Geradores de Padrão Central , Traumatismos da Medula Espinal , Ratos , Animais , Marcha/fisiologia , Medula Espinal/fisiologia , Extremidade Inferior , Membro Posterior
6.
J Mater Sci Mater Med ; 34(1): 4, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36586044

RESUMO

Autologous pericranium is a promising dural graft material. An optimal graft should exhibit similar mechanical properties to the native dura, but the mechanical properties of human pericranium have not been characterized, and studies of the biomechanical performance of human spinal dura are limited. The primary aim of this study was to measure the tensile structural and material properties of the pericranium, in the longitudinal and circumferential directions, and of the dura in each spinal region (cervical, thoracic and lumbar) and in three directions (longitudinal anterior and posterior, and circumferential). The secondary aim was to determine corresponding constitutive stress-strain equations using a one-term Ogden model. A total of 146 specimens were tested from 7 cadavers. Linear regression models assessed the effect of tissue type, region, and orientation on the structural and material properties. Pericranium was isotropic, while spinal dura was anisotropic with higher stiffness and strength in the longitudinal than the circumferential direction. Pericranium had lower strength and modulus than spinal dura across all regions in the longitudinal direction but was stronger and stiffer than dura in the circumferential direction. Spinal dura and pericranium had similar strain at peak force, toe, and yield, across all regions and directions. Human pericranium exhibits isotropic mechanical behavior that lies between that of the longitudinal and circumferential spinal dura. Further studies are required to determine if pericranium grafts behave like native dura under in vivo loading conditions. The Ogden parameters reported may be used for computational modeling of the central nervous system. Graphical abstract.


Assuntos
Fenômenos Mecânicos , Medula Espinal , Humanos , Fenômenos Biomecânicos/fisiologia , Medula Espinal/fisiologia , Coluna Vertebral , Dura-Máter , Resistência à Tração
7.
Front Neural Circuits ; 16: 1040070, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569798

RESUMO

Vertebrate locomotion presents a major challenge for maintaining visual acuity due to head movements resulting from the intimate biomechanical coupling with the propulsive musculoskeletal system. Retinal image stabilization has been traditionally ascribed to the transformation of motion-related sensory feedback into counteracting ocular motor commands. However, extensive exploration of spontaneously active semi-intact and isolated brain/spinal cord preparations of the amphibian Xenopus laevis, have revealed that efference copies (ECs) of the spinal motor program that generates axial- or limb-based propulsion directly drive compensatory eye movements. During fictive locomotion in larvae, ascending ECs from rostral spinal central pattern generating (CPG) circuitry are relayed through a defined ascending pathway to the mid- and hindbrain ocular motor nuclei to produce conjugate eye rotations during tail-based undulatory swimming in the intact animal. In post-metamorphic adult frogs, this spinal rhythmic command switches to a bilaterally-synchronous burst pattern that is appropriate for generating convergent eye movements required for maintaining image stability during limb kick-based rectilinear forward propulsion. The transition between these two fundamentally different coupling patterns is underpinned by the emergence of altered trajectories in spino-ocular motor coupling pathways that occur gradually during metamorphosis, providing a goal-specific, morpho-functional plasticity that ensures retinal image stability irrespective of locomotor mode. Although the functional impact of predictive ECs produced by the locomotory CPG matches the spatio-temporal specificity of reactive sensory-motor responses, rather than contributing additively to image stabilization, horizontal vestibulo-ocular reflexes (VORs) are selectively suppressed during intense locomotor CPG activity. This is achieved at least in part by an EC-mediated attenuation of mechano-electrical encoding at the vestibular sensory periphery. Thus, locomotor ECs and their potential suppressive impact on vestibular sensory-motor processing, both of which have now been reported in other vertebrates including humans, appear to play an important role in the maintenance of stable vision during active body displacements.


Assuntos
Movimentos Oculares , Reflexo Vestíbulo-Ocular , Animais , Humanos , Adulto , Reflexo Vestíbulo-Ocular/fisiologia , Locomoção/fisiologia , Natação/fisiologia , Xenopus laevis/fisiologia , Medula Espinal/fisiologia
8.
Elife ; 112022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36512397

RESUMO

Elaborate behaviours are produced by tightly controlled flexor-extensor motor neuron activation patterns. Motor neurons are regulated by a network of interneurons within the spinal cord, but the computational processes involved in motor control are not fully understood. The neuroanatomical arrangement of motor and premotor neurons into topographic patterns related to their controlled muscles is thought to facilitate how information is processed by spinal circuits. Rabies retrograde monosynaptic tracing has been used to label premotor interneurons innervating specific motor neuron pools, with previous studies reporting topographic mediolateral positional biases in flexor and extensor premotor interneurons. To more precisely define how premotor interneurons contacting specific motor pools are organized, we used multiple complementary viral-tracing approaches in mice to minimize systematic biases associated with each method. Contrary to expectations, we found that premotor interneurons contacting motor pools controlling flexion and extension of the ankle are highly intermingled rather than segregated into specific domains like motor neurons. Thus, premotor spinal neurons controlling different muscles process motor instructions in the absence of clear spatial patterns among the flexor-extensor circuit components.


The spinal cord contains circuits of nerve cells that control how the body moves. Within these networks are interneurons that project to motor neurons, which innervate different types of muscle to contract: flexors (such as the biceps), which bend, or 'flex', the body's joints, and extensors (such as the triceps), which lead to joint extension. These motor signals must be carefully coordinated to allow precise and stable control of the body's movements. Previous studies suggest that where interneurons are placed in the spinal cord depends on whether they activate the motor neurons responsible for flexion or extension. To test if these findings were reproducible, Ronzano, Skarlatou, Barriga, Bannatyne, Bhumbra et al. studied interneurons which flex and extend the ankle joint in mice. In collaboration with several laboratories, the team used a combination of techniques to trace how interneurons and motor neurons were connected in the mouse spinal cord. This revealed that regardless of the method used or the laboratory in which the experiments were performed, the distribution of interneurons associated with flexion and extension overlapped one another. This finding contradicts previously published results and suggests that interneurons in the spinal cord are not segregated based on their outputs. Instead, they may be positioned based on the signals they receive, similar to motor neurons. Understanding where interneurons in the spinal cord are placed will provide new insights on how movement is controlled and how it is impacted by injuries and disease. In the future, this knowledge could benefit work on how neural circuits in the spinal cord are formed and how they can be regenerated.


Assuntos
Interneurônios , Músculos , Medula Espinal , Animais , Camundongos , Interneurônios/fisiologia , Neurônios Motores/fisiologia , Raiva , Medula Espinal/fisiologia
9.
Elife ; 112022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36580075

RESUMO

Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In Drosophila, in contrast, sister neurons with different levels of Notch expression (NotchON/NotchOFF) develop distinct identities and diverge into separate circuits. Notch-differentiated sister neurons have been observed in vertebrate spinal cord and cerebellum, but whether they integrate into shared or distinct circuits remains unknown. Here, we evaluate how sister V2a (NotchOFF)/V2b (NotchON) neurons in the zebrafish integrate into spinal circuits. Using an in vivo labeling approach, we identified pairs of sister V2a/b neurons born from individual Vsx1+ progenitors and observed that they have somata in close proximity to each other and similar axonal trajectories. However, paired whole-cell electrophysiology and optogenetics revealed that sister V2a/b neurons receive input from distinct presynaptic sources, do not communicate with each other, and connect to largely distinct targets. These results resemble the divergent connectivity in Drosophila and represent the first evidence of Notch-differentiated circuit integration in a vertebrate system.


The brain is populated by neurons which are generated during embryonic development from cells called progenitors. Neurons that come from the same progenitor cell are considered to be 'sisters'. In certain brain regions of mice, sister neurons are often wired into shared networks, meaning they are more likely to receive input from the same neurons and connect with each other than non-sister cells. In contrast, in invertebrate animals, like the fruit fly, sister neurons often have different identities and are less likely to connect with each other. This may be because sister neurons in fruit flies often have varied levels of a protein called Notch, which plays an important role in establishing the identity of cells. Vertebrate and invertebrate animals are different in many respects, and it remained unclear whether Notch levels dictate which sister neurons connect together in vertebrates as they do in fruit flies. To investigate, Bello-Rojas and Bagnall studied two neurons in the spinal cord of zebrafish embryos which come from the same type of progenitor cell: the V2a neuron which has low levels of Notch, and the V2b neuron which has high levels of Notch. Fish, like humans, are vertebrates; however, their embryos are mostly transparent, making it easier to track how their neurons make connections during development using a microscope. This enabled Bello-Rojas and Bagnall to monitor whether V2a and V2b sister neurons joined the same network, like in other vertebrates, or different networks, akin to sister neurons in fruit flies which also have differing levels of Notch. Bello-Rojas and Bagnall found that sister V2a and V2b neurons stayed close to one another and seemed to connect through similar paths. However, closer investigation revealed that the sister neurons did not receive input from the same source. They also did not connect to each other or the same output neuron, suggesting that V2a and V2b sister neurons are part of different networks. This is the first time Notch levels have been shown to regulate which network a neuron will join in a vertebrate species. Since the V2a and V2b neurons are involved in controlling body movement, future work should determine whether adding progenitor cells that produce these neurons into the spinal cord could help the neuron network recover after injury or disease.


Assuntos
Interneurônios , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Interneurônios/fisiologia , Neurônios , Diferenciação Celular , Medula Espinal/fisiologia , Mamíferos
10.
Front Neural Circuits ; 16: 1076766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506594

RESUMO

In the past two decades we have learned an enormous amount of information regarding the identity of functional components of the neural circuitry responsible for generating locomotor activity in mammals. Molecular techniques, combined with classic electrophysiological and anatomical approaches, have resulted in the identification of a handful of classes of genetically defined interneuronal populations, and a delineation of the specific function of many of these during stepping. What lags behind at this point is a clear picture of the synaptic connectivity of each population, this information is key if we are to understand how the interneuronal components that are responsible for locomotor activity work together to form a functional circuit. In this mini review I will summarize what is, and what is not, known regarding the synaptic connectivity of each genetically defined interneuronal population that is involved in locomotion.


Assuntos
Geradores de Padrão Central , Animais , Geradores de Padrão Central/fisiologia , Medula Espinal/fisiologia , Locomoção/fisiologia , Interneurônios/fisiologia , Fenômenos Eletrofisiológicos , Mamíferos
11.
Elife ; 112022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-36512395

RESUMO

Spinal stimulation is a promising method to restore motor function after impairment of descending pathways. While paresis, a weakness of voluntary movements driven by surviving descending pathways, can benefit from spinal stimulation, the effects of descending commands on motor outputs produced by spinal stimulation are unclear. Here, we show that descending commands amplify and shape the stimulus-induced muscle responses and torque outputs. During the wrist torque tracking task, spinal stimulation, at a current intensity in the range of balanced excitation and inhibition, over the cervical enlargement facilitated and/or suppressed activities of forelimb muscles. Magnitudes of these effects were dependent on directions of voluntarily produced torque and positively correlated with levels of voluntary muscle activity. Furthermore, the directions of evoked wrist torque corresponded to the directions of voluntarily produced torque. These results suggest that spinal stimulation is beneficial in cases of partial lesion of descending pathways by compensating for reduced descending commands through activation of excitatory and inhibitory synaptic connections to motoneurons.


Assuntos
Neurônios Motores , Medula Espinal , Animais , Torque , Haplorrinos , Medula Espinal/fisiologia , Neurônios Motores/fisiologia , Músculo Esquelético/fisiologia , Estimulação Elétrica/métodos
12.
Nature ; 612(7940): 417-429, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36517712

RESUMO

The concept of immune privilege suggests that the central nervous system is isolated from the immune system. However, recent studies have highlighted the borders of the central nervous system as central sites of neuro-immune interactions. Although the nervous and immune systems both function to maintain homeostasis, under rare circumstances, they can develop pathological interactions that lead to neurological or psychiatric diseases. Here we discuss recent findings that dissect the key anatomical, cellular and molecular mechanisms that enable neuro-immune responses at the borders of the brain and spinal cord and the implications of these interactions for diseases of the central nervous system.


Assuntos
Encéfalo , Sistema Imunitário , Neuroimunomodulação , Encéfalo/imunologia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Sistema Imunitário/imunologia , Sistema Imunitário/fisiologia , Sistema Imunitário/fisiopatologia , Neuroimunomodulação/imunologia , Neuroimunomodulação/fisiologia , Medula Espinal/imunologia , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia , Humanos , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/psicologia
13.
Nature ; 611(7936): 540-547, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36352232

RESUMO

A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord1-3 applied during neurorehabilitation4,5 (EESREHAB) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EESREHAB in mice. We applied single-nucleus RNA sequencing6-9 and spatial transcriptomics10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type12,13 and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EESREHAB, whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours.


Assuntos
Neurônios , Paralisia , Traumatismos da Medula Espinal , Medula Espinal , Caminhada , Animais , Humanos , Camundongos , Neurônios/fisiologia , Paralisia/genética , Paralisia/fisiopatologia , Paralisia/terapia , Medula Espinal/citologia , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Caminhada/fisiologia , Estimulação Elétrica , Região Lombossacral/inervação , Reabilitação Neurológica , Análise de Sequência de RNA , Perfilação da Expressão Gênica
14.
PLoS One ; 17(11): e0277644, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36413525

RESUMO

Despite very different functions, studies increasingly report that there may be a potential central nervous anatomical connection between the heart and the small intestine. In this study, the central nervous anatomical relationship between the heart and small intestine was studied via a viral tracer. Pseudorabies virus (PRV) syngeneic strains with different fluorescent reporter genes (eGFP or mRFP) were microinjected into the heart walls and small intestinal walls of male C57BL/6J using glass microelectrode. The results showed that the co-labeled nuclei in the brain were lateral periaqueductal gray (LPAG) and ventrolateral periaqueductal gray (VLPAG) in the midbrain, mesencephalic trigeminal nucleus (Me5), and motor trigeminal nucleus anterior digastric Part (5Adi) in the pons. The co-labeled sites in the spinal cord were intermediolateral column (IML) in the second thoracic vertebra, IML and lamina 7 of the spinal gray (7SP) in the third thoracic vertebra, and IML in the fourth thoracic vertebra. Our data show that there is a neuroanatomical connection between the small intestine and the heart in the central nervous system (CNS). Neuroanatomical integration of the heart and small intestine may provide a basis for revealing the physiological and pathological interactions between the circulatory and digestive systems. The interactions may be mediated more effectively through sympathetic nerves.


Assuntos
Herpesvirus Suídeo 1 , Medula Espinal , Animais , Masculino , Vias Neurais , Medula Espinal/fisiologia , Substância Cinzenta Periaquedutal , Intestino Delgado
15.
J Neurosci ; 42(47): 8780-8794, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36202615

RESUMO

The mammalian brain contains numerous neurons distributed across forebrain, midbrain, and hindbrain that project axons to the lower spinal cord and work in concert to control movement and achieve homeostasis. Extensive work has mapped the anatomic location of supraspinal cell types and continues to establish specific physiological functions. The patterns of gene expression that typify and distinguish these disparate populations, however, are mostly unknown. Here, using adult mice of mixed sex, we combined retrograde labeling of supraspinal cell nuclei with fluorescence-activated nuclei sorting and single-nuclei RNA sequencing analyses to transcriptionally profile neurons that project axons from the brain to lumbar spinal cord. We identified 14 transcriptionally distinct cell types and used a combination of established and newly identified marker genes to assign an anatomic location to each. To validate the putative marker genes, we visualized selected transcripts and confirmed selective expression within lumbar-projecting neurons in discrete supraspinal regions. Finally, we illustrate the potential utility of these data by examining the expression of transcription factors that distinguish different supraspinal cell types and by surveying the expression of receptors for growth and guidance cues that may be present in the spinal cord. Collectively, these data establish transcriptional differences between anatomically defined supraspinal populations, identify a new set of marker genes of use in future experiments, and provide insight into potential differences in cellular and physiological activity across the supraspinal connectome.SIGNIFICANCE STATEMENT The brain communicates with the body through a wide variety of neuronal populations with distinct functions and differential sensitivity to damage and disease. We have used single-nuclei RNA sequencing technology to distinguish patterns of gene expression within a diverse set of neurons that project axons from the mouse brain to the lumbar spinal cord. The results reveal transcriptional differences between populations previously defined on the basis of anatomy, provide new marker genes to facilitate rapid identification of cell type in future work, and suggest distinct responsiveness of different supraspinal populations to external growth and guidance cues.


Assuntos
Axônios , Medula Espinal , Animais , Camundongos , Medula Espinal/fisiologia , Axônios/fisiologia , Núcleo Solitário , Neurônios , Mamíferos
17.
J Am Soc Nephrol ; 33(12): 2194-2210, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36253054

RESUMO

BACKGROUND: The kidneys critically contribute to body homeostasis under the control of the autonomic nerves, which enter the kidney along the renal vasculature. Although the renal sympathetic and sensory nerves have long been confirmed, no significant anatomic evidence exists for renal parasympathetic innervation. METHODS: We identified cholinergic nerve varicosities associated with the renal vasculature and pelvis using various anatomic research methods, including a genetically modified mouse model and immunostaining. Single-cell RNA sequencing (scRNA-Seq) was used to analyze the expression of AChRs in the renal artery and its segmental branches. To assess the origins of parasympathetic projecting nerves of the kidney, we performed retrograde tracing using recombinant adeno-associated virus (AAV) and pseudorabies virus (PRV), followed by imaging of whole brains, spinal cords, and ganglia. RESULTS: We found that cholinergic axons supply the main renal artery, segmental renal artery, and renal pelvis. On the renal artery, the newly discovered cholinergic nerve fibers are separated not only from the sympathetic nerves but also from the sensory nerves. We also found cholinergic ganglion cells within the renal nerve plexus. Moreover, the scRNA-Seq analysis suggested that acetylcholine receptors (AChRs) are expressed in the renal artery and its segmental branches. In addition, retrograde tracing suggested vagus afferents conduct the renal sensory pathway to the nucleus of the solitary tract (NTS), and vagus efferents project to the kidney. CONCLUSIONS: Cholinergic nerves supply renal vasculature and renal pelvis, and a vagal brain-kidney axis is involved in renal innervation.


Assuntos
Rim , Sistema Nervoso Simpático , Camundongos , Animais , Sistema Nervoso Simpático/fisiologia , Medula Espinal/fisiologia , Pelve , Colinérgicos
18.
Cell Rep ; 41(4): 111535, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36288693

RESUMO

Mechanisms underlying spontaneous locomotor recovery after spinal cord injury (SCI) remain unclear. Using adult zebrafish with complete SCI, we show that V2a interneurons regrow their axon to bridge the lesioned spinal segments in a subclass-specific and chronological order. Early after SCI, reestablishment of a unitary high-rhythm locomotor circuit is driven merely by axon-regrown fast V2a interneurons. Later, the reestablished intraspinal de novo circuit is organized into a modular design by axon-regrown fast and slow V2a interneurons rostral to the lesion, selectively driving caudal fast V2a/motor neurons and slow V2a/motor neurons, respectively. This orderly circuitry reestablishment determines the stepwise restoration of locomotor repertoire and recapitulates developmental processes. This progress can be interrupted by ablation of calretinin, a fast module-related protein, and accelerated by physical training. These findings suggest that promotion of axon regrowth of propriospinal V2a interneurons and establishment of de novo intraspinal circuits underpin the effectiveness of physical training in patients after SCI.


Assuntos
Traumatismos da Medula Espinal , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Calbindina 2 , Locomoção/fisiologia , Interneurônios/fisiologia , Medula Espinal/fisiologia
19.
Nature ; 610(7932): 526-531, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36224394

RESUMO

Although the generation of movements is a fundamental function of the nervous system, the underlying neural principles remain unclear. As flexor and extensor muscle activities alternate during rhythmic movements such as walking, it is often assumed that the responsible neural circuitry is similarly exhibiting alternating activity1. Here we present ensemble recordings of neurons in the lumbar spinal cord that indicate that, rather than alternating, the population is performing a low-dimensional 'rotation' in neural space, in which the neural activity is cycling through all phases continuously during the rhythmic behaviour. The radius of rotation correlates with the intended muscle force, and a perturbation of the low-dimensional trajectory can modify the motor behaviour. As existing models of spinal motor control do not offer an adequate explanation of rotation1,2, we propose a theory of neural generation of movements from which this and other unresolved issues, such as speed regulation, force control and multifunctionalism, are readily explained.


Assuntos
Neurônios Motores , Movimento , Rotação , Medula Espinal , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Medula Espinal/citologia , Medula Espinal/fisiologia , Caminhada/fisiologia , Neurônios Motores/fisiologia
20.
J Neural Eng ; 19(5)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36228593

RESUMO

Objective. Spinal cord injury (SCI) often results in debilitating movement impairments and neuropathic pain. Electrical stimulation of spinal neurons holds considerable promise both for enhancing neural transmission in weakened motor pathways and for reducing neural transmission in overactive nociceptive pathways. However, spinal stimulation paradigms currently under development for individuals living with SCI continue overwhelmingly to be developed in the context of motor rehabilitation alone. The objective of this study is to test the hypothesis that motor-targeted spinal stimulation simultaneously modulates spinal nociceptive transmission.Approach. We characterized the neuromodulatory actions of motor-targeted intraspinal microstimulation (ISMS) on the firing dynamics of large populations of discrete nociceptive specific and wide dynamic range (WDR) neurons. Neurons were accessed via dense microelectrode arrays implantedin vivointo lumbar enlargement of rats. Nociceptive and non-nociceptive cutaneous transmission was induced before, during, and after ISMS by mechanically probing the L5 dermatome.Main results. Our primary findings are that (a) sub-motor threshold ISMS delivered to spinal motor pools immediately modulates concurrent nociceptive transmission; (b) the magnitude of anti-nociceptive effects increases with longer durations of ISMS, including robust carryover effects; (c) the majority of all identified nociceptive-specific and WDR neurons exhibit firing rate reductions after only 10 min of ISMS; and (d) ISMS does not increase spinal responsiveness to non-nociceptive cutaneous transmission. These results lead to the conclusion that ISMS parameterized to enhance motor output results in an overall net decrease n spinal nociceptive transmission.Significance. These results suggest that ISMS may hold translational potential for neuropathic pain-related applications and that it may be uniquely suited to delivering multi-modal therapeutic benefits for individuals living with SCI.


Assuntos
Neuralgia , Traumatismos da Medula Espinal , Estimulação da Medula Espinal , Ratos , Animais , Medula Espinal/fisiologia , Traumatismos da Medula Espinal/reabilitação , Estimulação da Medula Espinal/métodos , Estimulação Elétrica/métodos , Neuralgia/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...