Perspectives on repair and protection against damage to neural circuits

The elucidation of molecular mechanisms guiding neural circuit formation, from the cloning of Trk receptors and netrin, to chemotactic cues shaping axon pathways, and the midline switch of commissural axons, defined a landmark era in developmental neurobiology.
These findings outlined the molecular basis of precise circuit wiring in early development. Today, the challenge remains: can we achieve an integrated understanding of how neural circuits are formed, maintained, and repaired across the full human lifespan, from development through aging and into disease states?

This Research Topic aims to connect developmental mechanisms with adult circuit stability and regenerative capacity.
To address this, we seek contributions that investigate how various biological systems collectively influence circuit robustness and repair. These include glial-neuronal interactions, intracellular cytoskeletal and membrane dynamics, mitochondrial and metabolic control of neuronal health, and the epigenetic regulation of gene expression in injury contexts.

By anchoring developmental insights into adult models of injury, neurodegeneration, and age-associated decline, this collection will help define the conditions and mechanisms that either enable or restrict circuit recovery.
By bridging molecular, cellular, and systemic viewpoints, we aim to offer a high-resolution synthesis of how neural circuits are preserved or compromised across time and condition. The goal is to build a cumulative understanding that directly informs therapeutic strategies for restoring or protecting circuit function in clinical and translational contexts.

To this aim, we welcome articles focusing on the following:

• Neurotrophin signaling and lifespan circuit plasticity
Focus on the temporal extension of neurotrophic signaling (e.g., Trk receptors) and its role in adult and aging brain circuit maintenance.
• Axon guidance mechanisms in adult regeneration
Revisit classical axon guidance molecules (e.g., netrins, semaphorins) in the context of adult CNS injury and regeneration.
• Glia-circuit interactions in damage response and repair
Examine the active role of astrocytes, microglia, and oligodendrocytes in both maladaptive and protective responses to circuit disruption.
• Metabolic control of synaptic stability and plasticity
Investigate how local and systemic metabolic states affect synapse formation, maintenance, and vulnerability.
• Epigenetic regulation of circuit resilience across the lifespan
Focus on chromatin dynamics and non-coding RNA mechanisms that regulate the capacity of neurons to respond to damage or stress.
• Cytoskeletal remodeling and membrane dynamics after injury
Explore how actin, microtubule systems, and membrane trafficking enable or constrain recovery of structural connectivity.
• Neural circuit rewiring in models of neurodevelopmental disorders
How circuit miswiring occurs in autism, schizophrenia, and related disorders, and the potential for late-life correction.
• Aging-associated decline in neural circuit repair mechanisms
Identify specific age-related losses in intrinsic or extrinsic repair programs, including changes in trophic factor signaling and inflammatory tone.
• Bioelectrical and oscillatory homeostasis in circuit function and repair
The role of local field potentials and oscillatory synchrony in maintaining functional connectivity, and how these are disrupted and potentially restored.
• Synthetic and bioengineered strategies for circuit reconstruction
Development of neural scaffolds, cell therapy, and precision molecular tools (e.g., optogenetics, chemogenetics) for rebuilding lost circuits.

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
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

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: axon regeneration, degenerative diseases, axon degeneration, repair, protection, neural circuits

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.