Scaling Our World View: How Monoamines Can Put Context Into Brain Circuitry

Monoamines are presumed to be diffuse metabotropic neuromodulators of the topographically and temporally precise ionotropic circuitry which dominates CNS functions. Their malfunction is strongly implicated in motor and cognitive disorders, but their function in behavioral and cognitive processing is scarcely understood. In this paper, the principles of such a monoaminergic function are conceptualized for locomotor control. We find that the serotonergic system in the ventral spinal cord scales ionotropic signals and shows topographic order that agrees with differential gain modulation of ionotropic subcircuits. Whereas the subcircuits can collectively signal predictive models of the world based on life-long learning, their differential scaling continuously adjusts these models to changing mechanical contexts based on sensory input on a fast time scale of a few 100 ms. The control theory of biomimetic robots demonstrates that this precision scaling is an effective and resource-efficient solution to adapt the activation of individual muscle groups during locomotion to changing conditions such as ground compliance and carried load. Although it is not unconceivable that spinal ionotropic circuitry could achieve scaling by itself, neurophysiological findings emphasize that this is a unique functionality of metabotropic effects since recent recordings in sensorimotor circuitry conflict with mechanisms proposed for ionotropic scaling in other CNS areas. We substantiate that precision scaling of ionotropic subcircuits is a main functional principle for many monoaminergic projections throughout the CNS, implying that the monoaminergic circuitry forms a network within the network composed of the ionotropic circuitry. Thereby, we provide an early-level interpretation of the mechanisms of psychopharmacological drugs that interfere with the monoaminergic systems.