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  1. We describe and analyze a computational model of neural circuits in the mammalian spinal cord responsible for generating and shaping locomotor-like oscillations. The model represents interacting populations of spinal neurons, including the neurons that were genetically identified and characterized in a series of previous experimental studies. Here, we specifically focus on the ipsilaterally projecting V1 interneurons, their possible role in the spinal locomotor circuitry, and their involvement in the generation of locomotor oscillations. The proposed connections of these neurons and their involvement in different neuronal pathways in the spinal cord allow the model to reproduce the results of optogenetic manipulations of these neurons under different experimental conditions. We suggest the existence of two distinct populations of V1 interneurons mediating different ipsilateral and contralateral interactions within the spinal cord. The model proposes explanations for multiple experimental data concerning the effects of optogenetic silencing and activation of V1 interneurons on the frequency of locomotor oscillations in the intact cord and hemicord under different experimental conditions. Our simulations provide an important insight into the organization of locomotor circuitry in the mammalian spinal cord.
    Free, publicly-accessible full text available May 1, 2023
  2. Speed-dependent interlimb coordination allows animals to maintain stable locomotion under different circumstances. The V3 neurons are known to be involved in interlimb coordination. We previously modeled the locomotor spinal circuitry controlling interlimb coordination (Danner et al., 2017). This model included the local V3 neurons that mediate mutual excitation between left and right rhythm generators (RGs). Here, our focus was on V3 neurons involved in ascending long propriospinal interactions (aLPNs). Using retrograde tracing, we revealed a subpopulation of lumbar V3 aLPNs with contralateral cervical projections. V3 OFF mice, in which all V3 neurons were silenced, had a significantly reduced maximal locomotor speed, were unable to move using stable trot, gallop, or bound, and predominantly used a lateral-sequence walk. To reproduce this data and understand the functional roles of V3 aLPNs, we extended our previous model by incorporating diagonal V3 aLPNs mediating inputs from each lumbar RG to the contralateral cervical RG. The extended model reproduces our experimental results and suggests that locally projecting V3 neurons, mediating left–right interactions within lumbar and cervical cords, promote left–right synchronization necessary for gallop and bound, whereas the V3 aLPNs promote synchronization between diagonal fore and hind RGs necessary for trot. The model proposes the organizationmore »of spinal circuits available for future experimental testing.« less
    Free, publicly-accessible full text available April 27, 2023
  3. Mammalian locomotion is generated by central pattern generators (CPGs) in the spinal cord, which produce alternating flexor and extensor activities controlling the locomotor movements of each limb. Afferent feedback signals from the limbs are integrated by the CPGs to provide adaptive control of locomotion. Responses of CPG-generated neural activity to afferent feedback stimulation have been previously studied during fictive locomotion in immobilized cats. Yet, locomotion in awake, behaving animals involves dynamic interactions between central neuronal circuits, afferent feedback, musculoskeletal system, and environment. To study these complex interactions, we developed a model simulating interactions between a half-center CPG and the musculoskeletal system of a cat hindlimb. Then, we analyzed the role of afferent feedback in the locomotor adaptation from a dynamic viewpoint using the methods of dynamical systems theory and nullcline analysis. Our model reproduced limb movements during regular cat walking as well as adaptive changes of these movements when the foot steps into a hole. The model generates important insights into the mechanism for adaptive locomotion resulting from dynamic interactions between the CPG-based neural circuits, the musculoskeletal system, and the environment.
    Free, publicly-accessible full text available April 8, 2023
  4. Neuronal circuits in the spinal cord are essential for the control of locomotion. They integrate supraspinal commands and afferent feedback signals to produce coordinated rhythmic muscle activations necessary for stable locomotion. For several decades, computational modeling has complemented experimental studies by providing a mechanistic rationale for experimental observations and by deriving experimentally testable predictions. This symbiotic relationship between experimental and computational approaches has resulted in numerous fundamental insights. With recent advances in molecular and genetic methods, it has become possible to manipulate specific constituent elements of the spinal circuitry and relate them to locomotor behavior. This has led to computational modeling studies investigating mechanisms at the level of genetically defined neuronal populations and their interactions. We review literature on the spinal locomotor circuitry from a computational perspective. By reviewing examples leading up to and in the age of molecular genetics, we demonstrate the importance of computational modeling and its interactions with experiments. Moving forward, neuromechanical models with neuronal circuitry modeled at the level of genetically defined neuronal populations will be required to further unravel the mechanisms by which neuronal interactions lead to locomotor behavior.