The myelination of axons by oligodendrocytes profoundly affects central nervous system function, but how this is regulated by neuronal activity in vivo is not known. Here we find that blocking synaptic vesicle release impairs CNS myelination by reducing the number of myelin sheaths made by individual oligodendrocytes during their short period of formation. We also find that stimulating neuronal activity increases myelin sheath formation by individual oligodendrocytes. These data show that neuronal activity regulates the myelinating capacity of single oligodendrocytes.

Spinal circuits generate locomotion with variable speed as circumstances demand. These circuits have been assumed to convey equal and uniform excitation to all motoneurons whose input resistance dictates their activation sequence. However, the precise connectivity pattern between excitatory premotor circuits and the different motoneuron types has remained unclear. Here, we generate a connectivity map in adult zebrafish between the V2a excitatory interneurons and slow, intermediate, and fast motoneurons. We show that the locomotor network does not consist of a uniform circuit as previously assumed. Instead, it can be deconstructed into three separate microcircuit modules with distinct V2a interneuron subclasses driving slow, intermediate, or fast motoneurons. This modular design enables the increase of locomotor speed by sequentially adding microcircuit layers from slow to intermediate and fast. Thus, this principle of organization of vertebrate spinal circuits represents an intrinsic mechanism to increase the locomotor speed by incrementally engaging different motor units.

Locomotor movements are coordinated by a network of neurons that produces sequential muscle activation. Different motoneurons need to be recruited in an orderly manner to generate movement with appropriate speed and force. However, the mechanisms governing the recruitment order have not been fully clarified. Here we show, using an in vitro juvenile/adult zebrafish brainstem-spinal cord preparation, that motoneurons are organized in four pools with specific topographic locations and are incrementally recruited to produce swimming at different frequencies. The threshold of recruitment is not dictated by the input resistance of motoneurons but is rather set by a combination of specific biophysical properties and the strength of the synaptic currents. Thus, our results provide insights into the cellular and synaptic computations governing recruitment of motoneurons during locomotion.3

In vertebrates, spinal circuits drive rhythmic firing in motoneurons in the appropriate sequence to produce locomotor movements. These circuits become active early during development and mature gradually to acquire the flexibility necessary to accommodate the increased behavioral repertoire of adult animals. The focus here is to elucidate how different pools of motoneurons are organized and recruited and how membrane properties contribute to their mode of operation. For this purpose, we have used the in vitro preparation of adult zebrafish. We show that different motoneuron pools are organized in a somatotopic fashion in the motor column related to the type of muscle fibers (slow, intermediate, fast) they innervate. During swimming, the different motoneuron pools are recruited in a stepwise manner from slow, to intermediate, to fast to cover the full range of locomotor frequencies seen in intact animals. The spike threshold, filtering properties, and firing patterns of the different motoneuron pools are graded in a manner that relates to their order of recruitment. Our results thus show that motoneurons in adult zebrafish are organized into distinct modules, each with defined locations, properties, and recruitment patterns tuned to precisely match the muscle properties and hence produce swimming of different speeds and modalities.

Neural networks in the spinal cord can generate locomotion in the absence of rhythmic input from higher brain structures or sensory feedback because they contain an intrinsic source of excitation. However, the molecular identity of the spinal interneurons underlying the excitatory drive within the locomotor circuit has remained unclear. Using optogenetics, we show that activation of a molecularly defined class of ipsilateral premotor interneurons elicits locomotion. These interneurons represent the excitatory module of the locomotor networks and are sufficient to produce a coordinated swimming pattern in zebrafish. They correspond to the V2a interneuron class and express the transcription factor Chx10. They produce sufficient excitatory drive within the spinal networks to generate coordinated locomotor activity. Therefore, our results define the V2a interneurons as the excitatory module within the spinal locomotor networks that is sufficient to initiate and maintain locomotor activity.