Neural circuits translate the activity of individual synapses into coherent patterns of behavior. Synaptic plasticity governs how information is encoded and integrated at the microscopic level, while interconnected circuits sustain primarily motor control at the meso- and macroscopic levels. Disruption of this delicate balance, whether due to traumatic injury, tumor growth, inflammation, or therapeutic interventions, compromises circuit dynamics and leads to measurable impairments in motor performance and coordination. Recent technological and conceptual advances, including high-resolution imaging, multi-omics integration, and computational approaches to circuit analysis, now enable unprecedented insight into how these micro- and macro-level processes interact.

This editorial project focuses on synaptic and circuit-level mechanisms underlying motor functions, launched in conjunction with the eighth BraYn Conference, held at The Polytechnic University of Turin (October 29-31). We especially encourage submissions from conference participants to showcase and further develop the work presented during the event.

This Research Topic seeks to bridge cellular and molecular mechanisms with circuit-level and behavioral analyses, clarifying how synaptic plasticity governs adaptive and maladaptive motor functions. For example, in vitro approaches, such as patient-derived organoids and 3D cultures, have been pivotal in elucidating the cellular mechanisms underlying brain tumor and radiotherapy-associated neuronal impairments that alter motor circuit activity. Similarly, experimental models of neuromuscular junction remodeling and traumatic brain injury have shown how synaptic dysfunction propagates across circuits and impairs motor coordination and performance. Recent advances in imaging, multi-omics, and motor assays have now allowed the integration of cellular changes with motor outcomes, bridging mechanistic details at the circuit level.

By emphasizing the contribution of both central and peripheral nervous systems in synaptic and inflammatory disturbances, recent work has demonstrated how diverse pathological processes converge on shared circuit dysfunctions. Therefore, a critical step is to understand how diverse neuronal circuits interact through communal regulatory processes at the synaptic level. This insight is key to revealing the mechanisms of pathological synaptotoxicity and guiding efficient therapeutic strategies to restore motor function.

This Research Topic aims to provide perspective on the cellular and molecular bases of circuit activity and their translation into motor functions and dysfunctions. By combining innovative in vitro and in vivo models with mechanistic and translational approaches, the collection will highlight how synaptic and circuit-level processes define motor outcomes across health and disease.

We encourage contributions on, but not limited to, the following subject areas:

• Mechanisms of synaptic plasticity in motor control and neuromuscular function
• Motor circuit remodeling in inflammatory, oncological, and traumatic conditions
• Organoid, slice, and 3D culture models of synaptic and circuit alterations relevant to movement
• Integration of imaging, electrophysiology, and multi-omics to map circuit dynamics
• Translational studies linking synaptic pathology to motor impairment and dysfunction

Are you interested in contributing a manuscript to this Research Topic?

Synapses in action: Mechanistic and translational insights into motor functions - Insights from the BraYn Conference 2025

Topic Coordinator