Generation and selection of motor behaviors neural circuits and endocannabinoid modulation

The generation of basic motor behavior relies on the activation of spinal neuronal networks called central pattern generators (CPGs). Descending drive from higher brain areas activates the spinal CPG to generate motor behavior. In the face of changes in the environment, animals make constant motor behavioral selection. Both the generation and selection of motor behavior are performed by activating hard-wired neural circuits, whose activity is further refined by neuromodulation. In this thesis, we use the spinal locomotor networks in lamprey and zebrafish to explore the neural mechanisms underlying the generation and selection of motor behaviors. Firstly, in lamprey spinal locomotor circuits, we show that the release of endocannabinoids increases the excitability of the spinal locomotor network by depressing inhibitory synaptic transmission and potentiating excitatory synaptic transmission. Secondly, we show that the behavioral selection between escape and swimming in zebrafish is mediated by a hard-wired circuit. This circuit is supplemented with endocannabinoid modulation that promotes escape and suppresses swimming. Thirdly, we uncover a novel modular organization of the spinal locomotor circuit. We demonstrate a selective pattern of connectivity between excitatory V2a interneurons and motoneurons segregating them into slow, intermediate and fast sub-circuit modules. Fourthly, we show the existence of electrical coupling between motoneurons and excitatory V2a interneurons, which extends motoneurons influence onto premotor V2a interneurons. This enables motoneurons to become embedded in the spinal circuits generating the locomotor rhythm. Overall this thesis provides insight into the mechanism of generation and selection of motor behaviors.

List of scientific papers

I. Song, J., Kyriakatos, A., and El Manira, A. (2012). Gating the polarity of endocannabinoid-mediated synaptic plasticity by nitric oxide in the spinal locomotor network. J. Neurosci. 32, 5097-5105.
https://doi.org/10.1523/JNEUROSCI.5850-11.2012

II. Song, J., Ampatzis, K., Ausborn, J., and El Manira, A. Endocannabinoids supplement a hardwired circuit to encode behavioral choice in zebrafish. [Manuscript]

III. Ampatzis, K., Song, J. (co-first author), Ausborn, J., and El Manira, A. (2014). Separate microcircuit modules of distinct V2a interneurons and motoneurons control the speed of locomotion. Neuron 83, 934-943.
https://doi.org/10.1016/j.neuron.2014.07.018

IV. Song, J., Ampatzis, K., and El Manira, A. Motoneurons control of the rhythm generating circuit in the spinal cord. [Manuscript]