Abstract :
[en] Neurons depend on two interdependent mechanisms-homeostasis and
neuromodulation-to maintain robust and adaptable functionality. Homeostasis
stabilizes neuronal activity by adjusting ionic conductances, whereas
neuromodulation dynamically modifies ionic properties in response to external
signals. Combining these mechanisms in conductance-based models often produces
unreliable outcomes, particularly when sharp neuromodulation interferes with
homeostatic tuning. This study explores how a biologically inspired
neuromodulation controller can harmonize with homeostasis to ensure reliable
neuronal function. Using computational models of stomatogastric ganglion and
dopaminergic neurons, we demonstrate that controlled neuromodulation preserves
neuronal firing patterns while maintaining intracellular calcium levels. Unlike
sharp neuromodulation, the neuromodulation controller integrates
activity-dependent feedback through mechanisms mimicking G-protein-coupled
receptor cascades. The interaction between these controllers critically depends
on the existence of an intersection in conductance space, representing a
balance between target calcium levels and neuromodulated firing patterns.
Maximizing neuronal degeneracy enhances the likelihood of such intersections,
enabling robust modulation and compensation for channel blockades. We further
show that this controller pairing extends to network-level activity, reliably
modulating central pattern generators in crustaceans. These findings suggest
that targeting neuromodulation pathways-rather than ion channels directly-may
offer safer pharmacological strategies to manage neuronal dysfunctions. This
study highlights the complementary roles of homeostasis and neuromodulation,
proposing a unified control framework for maintaining robust and adaptive
neural activity under physiological and pathological conditions.
