Structural Organization of Spinal Cord Circuits in Health and Disease

The spinal cord is one of the most architecturally complex structures in the central nervous system. Its highly organized laminar arrangement, precisely stratified synaptic inputs, and diverse neuronal populations underlie a remarkable range of functions — from the modulation of pain and somatosensory information processing in the dorsal horn to the coordination of motor output in the ventral horn. Despite decades of investigation, fundamental questions remain about how this structural organisation is established, how it sustains sensorimotor function in the healthy animal, and how it is reorganised under conditions of injury or disease.

Recent advances have reshaped our understanding at multiple levels. Morpho-functional characterisation of dorsal horn interneurons has revealed previously unappreciated diversity in axon trajectories, dendritic geometry, and laminar distribution — from laminae I–II projection neurons and local-circuit cells to neurons of the intermediate and lateral horn. Work mapping the spatial distributions of local axon collaterals of lamina I neurons has clarified how these cells contribute to intra-spinal signal integration beyond their classical roles as relay neurons to supraspinal centres. Simultaneously, contralateral afferent inputs, propriospinal connectivity, and the laminar specificity of C-fibre and Aδ-fibre projections have been re-examined with single-cell resolution, expanding the known connectivity of sensory circuits.

On the motor side, the structural consequences of root avulsion, contusion, and motoneuron pool depletion have been tracked in quantitative detail: how far a motoneuron pool can be reduced before functionally useful reinnervation fails; how the structural microenvironment — inflammasome activation, excitotoxic receptor expression, astro- and microglial reactivity — shapes the capacity of surviving motoneurons to extend new axons; and how biological interventions (neurotrophic factors, stem cell secretomes, nucleoside-modified mRNA delivery) alter the structural outcome of injury. These translational threads run from basic circuit anatomy all the way to pre-clinical restoration of motor function.

Epigenetic and molecular mechanisms are also emerging as structural determinants. Modifications of spinal dynorphinergic interneurons via histone mutagenesis, and changes in KCC2 (potassium-chloride co-transporter 2) distribution following ventral root injury, demonstrate that disease does not simply interruptsremove circuits — it remodels them at the subcellular level, shifting inhibitory balance and reshaping receptor landscapes in ways that are only beginning to be understood anatomically.

This Research Topic brings together work on both the healthy and the diseased spinal cord to address questions raised be the above recent findings including the following:
o How are spinal cord neurons — interneurons, projection neurons, motoneurons — structurally organised within and across laminae, and what do their axon morphology and dendritic fields predict about their functional roles?
o What afferent inputs reach each laminar compartment, how are they distributed and integrated across the dorsoventral and rostrocaudal axes, and how does this vary between species or developmental stages?
o How does injury (contusion, root avulsion, ischaemia, neurodegeneration) alter the structural connectivity of sensory and motor circuits, and what are the structural correlates of functional deficit?
o What are the cellular and molecular mechanisms — including epigenetic regulation, neuroinflammatory remodelling, and neurotrophic factor signalling — that determine structural and functional plasticity or degeneration in the diseased spinal cord?
o What anatomical evidence supports translational strategies aimed at restoring circuit integrity, including stem cell transplantation, mRNA- and anti-excitotoxicity based neuroprotection, and peripheral nerve reconnection?

We welcome Original Research, Reviews, Systematic Reviews, and Methods articles addressing spinal cord circuit anatomy at any level of organisation — from subcellular receptor distribution to whole-circuit connectivity — in health, injury, disease, or repair. Studies using histochemical, electrophysiological, imaging, molecular, or computational approaches are all in scope. Both rodent and human data are of interest, as are comparative studies across model systems.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Neuroplasticity, Spinal cord circuits, Dorsal horn, Ventral horn, Interneurons, Motoneurons, Spinal cord injury, Afferent pathways

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.