The mechanisms of electrical neuromodulation

The central and peripheral nervous systems are specialized to conduct electrical currents that underlie behaviour. When this multidimensional electrical system is disrupted by degeneration, damage, or disuse, externally applied electrical currents may act to modulate neural structures and provide therapeutic benefit. The administration of electrical stimulation can exert precise and multi-faceted effects at cellular, circuit and systems levels to restore or enhance the functionality of the central nervous system by providing an access route to target specific cells, fibres of passage, neurotransmitter systems, and/or afferent/efferent communication to enable positive changes in behaviour. Here we examine the neural mechanisms that are thought to underlie the therapeutic effects seen with current neuromodulation technologies. To gain further insights into the mechanisms associated with electrical stimulation, we summarize recent findings from genetic dissection studies conducted in animal models. KEY POINTS: Electricity is everywhere around us and is essential for how our nerves communicate within our bodies. When nerves are damaged or not working properly, using exogenous electricity can help improve their function at distinct levels - inside individual cells, within neural circuits, and across entire systems. This method can be tailored to target specific types of cells, nerve fibres, neurotransmitters and communication pathways, offering significant therapeutic potential. This overview explains how exogenous electricity affects nerve function and its potential benefits, based on research in animal studies. Understanding these effects is important because electrical neuromodulation plays a key role in medical treatments for neurological conditions.