Principles of recruitment in the adult zebrafish spinal cord
Zusammenfassung der Projektergebnisse
The goal of this project was to gain insights into the organization and function of the spinal locomotor networks. In particular, we aimed at elucidating the principles that define the order of recruitment of motoneurons and interneurons to produce locomotor movements with appropriate speed, force and timing. To achieve these goals we first developed a juvenile/adult zebrafish brainstemspinal cord preparation in which we used a stimulation protocol to induce highly physiological locomotor activity in vitro that enabled us to elicit a wide range of locomotor frequencies. Changing locomotor speed ultimately involves a sequential activation of different motoneurons that represent the final stage of processing in the spinal cord. We determined the pattern of recruitment of motoneurons in juvenile/adult zebrafish and investigated the synaptic and cellular properties that govern their recruitment. We provide now a more sophisticated view than the simplest idea that input resistance determines recruitment order of motoneurons. Rather, intrinsic properties and synaptic drive of the motoneurons vary across the population so that different functional pools emerge. Motoneurons are not primarily involved in the generation of the locomotor rhythm, which is considered to be generated by ipsilateral excitatory interneurons whose identity has been elusive. V2a interneurons are a class of premotor interneurons found in the zebrafish spinal cord which have been implicated in the production of swimming. Partial ablation of these interneurons in zebrafish increased the threshold of induction of swimming activity and decreased the burst frequency. Thus, changes in the speed of locomotor movements would be initiated at the level of V2a interneurons. We have therefore investigated how V2a interneurons are recruited at different swimming speeds in the juvenile/adult zebrafish. Our findings show that although the excitatory drive of V2a interneurons is graded topographically, their order of recruitment does not obey a topographic map, unlike that of motoneurons. Rather, their recruitment threshold is set by a scaling of the excitatory drive by the input resistance, which results in a non-topographic incremental recruitment of V2a interneurons to cover the full range of swimming frequencies. Overall, results from this project provide fundamental insights into the rules of recruitment of neurons and the influence of cellular and synaptic processing in a mature spinal network.
Projektbezogene Publikationen (Auswahl)
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(2011). Initiation of Locomotion in Adult Zebrafish. The Journal of Neuroscience 31, 8422 –8431
Kyriakatos, A., Mahmood, R., Ausborn, J., Porres, C.P., Büschges, A., and El Manira, A.
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(2011). Principles governing recruitment of motoneurons during swimming in zebrafish. Nat Neurosci 14, 93–99
Gabriel, J.P., Ausborn, J., Ampatzis, K., Mahmood, R., Eklof-Ljunggren, E., and El Manira, A.
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(2012). Origin of excitation underlying locomotion in the spinal circuit of zebrafish. PNAS 109, 5511–5516
Eklöf-Ljunggren, E., Haupt, S., Ausborn, J., Dehnisch, I., Uhlén, P., Higashijima, S., and Manira, A.E.