Biology subjects

Winther, A.

Publications and source records attributed to Winther, A..

3 recordsLinked to original sources

bioRxiv2026

Spinal circuit regionalization diversifies motor output along the vertebrate body axis

The evolution of the vertebrate limb-torso-limb body plan drove a diversification of motor behavior. How neural circuits are organized to generate distinct outputs across body regions, however, remains unknown. Here, we construct a cross-species, spatiotemporal atlas of spinal interneurons spanning the rostrocaudal and developmental axes of frogs and mice. We uncover a common framework of interneuron regionalization that mirrors each vertebrates body plan and arises through Hox-dependent regulation of rostrocaudal neurogenesis. Combining electrophysiology with computational modeling, we show that changing regional circuit composition is sufficient to respecify motor output. Together, these findings establish a causal link between developmental patterning, circuit architecture, and motor function, identifying interneuron regionalization as a fundamental organizational principle linking body-plan evolution to motor diversity.

neuroscience↗

bioRxiv2025

Neural manifolds that orchestrate walking and stopping

Walking, stopping and maintaining posture are essential motor behaviors, yet the underlying neural processes remain poorly understood. Here, we investigate neural activity behind locomotion and its walk-to-stop transition. Based on a new theory of the lumbar spinal cord1, 2 we propose and predict that spinal population activity contains limit cycle dynamics to drive walking and fixed-point attractors for stopping. To test these predictions we record neural activity in lumbar cord of freely moving rats using Neuropixels probes3. To control stopping, we stimulate a brainstem nucleus, known to induce motor arrest4-7. We find: During locomotion, the population activity of lumbar spinal neurons exhibits rotational dynamics8-10. These dynamics unfold within a low-dimensional locomotor manifold11, 12, a looping set of trajectories that serves as the repeating signature of locomotion, that also behaves as a limit-cycle attractor. Shortly before stopping, the neural state rapidly changes from the locomotor manifold to a postural fixed point attractor. When kicking the state out of the fixed point using perturbations it shifts to a nearby albeit different fixed point. Repeated stoppings form a local quasi-continuum of fixed points representing various poses - i.e. a postural manifold. These observations are in agreement with our theory, which further indicates the mechanistic roles for subpopulations of spinal interneurons for controlling walking and stopping. Besides explaining the data, our theory makes further predictions to be tested in future experiments.

neuroscience↗

bioRxiv2024

Spatial and network principles behind neural generation of locomotion

Generation of locomotion is a fundamental function of the spinal cord, yet the underlying principles remain unclear. In particular, the relationship between neuronal cell types, networks and functions has been difficult to establish1,2. Here, we propose principles by which functions arise primarily from spatial features of the cord. First, we suggest that projections of distinct cell types constitute an asymmetrical "Mexican hat" topology, i.e. local excitation and surrounding inhibition with dissimilar length of projection along the rostro-caudal axis. Second, this projection topology constitutes the mechanism of rhythm- and pattern generation of mammalian locomotion. Third, the role of segregation of cell types in the transversal plane is for descending fibers to find appropriate targets. Modulation of these targets allows control of motor activity by adjusting the symmetry of the projection topology. We extract these principles via a model of the mouse spinal cord, where networks are constructed by probabilistic sampling of synaptic connections from cell-specific projection patterns, which are based on previous studies3, 4. The cell-type distributions are derived from single-cell RNA sequencing combined with spatial transcriptomics5. We find that essential aspects of locomotion are readily reproduced and controlled without requiring parameter optimization, and several experimental observations can now be explained mechanistically. Further, two main features are predicted: propagating bumps of neural activity during rhythmical activity and formation of static bumps during arrest and posture. Besides linking cell types, structure and function, we propose our approach as a new theoretical framework for motor control.

neuroscience↗