Spinal cholinergic interneurons differentially control motoneuron excitability and alter the locomotor network operational range

Summary: While cholinergic neuromodulation is important for locomotor circuit operation, the specific neuronal mechanisms that acetylcholine employs to regulate and fine-tune the speed of locomotion are largely unknown. Here, we show that cholinergic interneurons are present in the zebrafish spinal cord and differentially control the excitability of distinct classes of motoneurons (slow, intermediate and fast) in a muscarinic dependent manner. Moreover, we reveal that m2-type muscarinic acetylcholine receptors (mAChRs) are present in fast and intermediate motoneurons, but not in the slow motoneurons, and that their activation decreases neuronal firing. We also provide evidence that this configuration of motoneuron muscarinic receptors serves as the main intrinsic plasticity mechanism to alter the operational range of motoneuron modules. These unexpected findings provide new insights into the functional flexibility of motoneurons and how they execute locomotion at different speeds.