THE MODULATION OF LOCOMOTORCENTRAL PATTERN GENERATORS BYOCTOPAMINE AND TYRAMINE INDROSOPHILA LARVAE

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Abstract

Movement is controlled by neuronal central pattern generator (CPG) networks that are segmentally organised in organisms across the animal kingdom. The precise role of neuromodulators in the function, development and, particularly, the maintenance of these circuits is currently unresolved. This study investigates the effects of chronically altered signalling of tyramine and/or octopamine, two well established neuromodulators, in Drosophila larval locomotion. It shows that tyramine reduces crawling speed in larvae, whereas octopamine increases speed up to a physiological maximum. Changes in crawling speed are mediated by modulating stride duration, whilst stride length remains constant. These two neuromodulators also affect segmental muscle contraction and relaxation rates, indicative that the effects on crawling speed are likely to be at least partially due to modulatory effects on muscle physiology. Muscle recordings from muscle M6 in two adjacent segments, during fictive forward locomotion show that stride duration is influenced by a variable time delay between segmental CPG outputs. Frequency and duration of individual segmental outputs, by contrast, remains constant. The behavioural and electrophysiological data suggest, therefore, that the segmental locomotor CPG outputs remain constant in response to chronically altered neuromodulatory signalling. This study also identified a close spatial proximity of motor neuronal dendritic branches and putatively octopaminergic and/or tyraminergic synaptic terminal varicosities in the ventral nerve cord (VNC) neuropil. Moreover, manipulation of a putatively octopaminergic and/or tyraminergic subpopulation of interneurons, located in anterior brain regions, is sufficient to induce a similar, albeit smaller, larval crawling deficit. This indicates that the effects of locomotion may be induced in the central nervous system. This is confirmed in identified motor neurons as chronic changes in octopaminergic and/or tyraminergic signalling increase the frequency of bursting of action potential firing. In addition, the synaptic current amplitudes are substantially reduced in both ventral and dorsal muscle- innervating motor neurons, indicative of an effect to presynaptic excitation. In contrast, the function of neuromuscular junction remains largely unchanged. Taken together, this data shows that neuromodulation is sufficient to alter the output of a relatively small group of neurons, that comprise the locomotor CPG. The site of action of these modulators is, however, likely to be diverse.

Layman's Abstract

Movement is controlled by neuronal central pattern generators (CPG), which are small neuronal networks that coordinate their specific target muscle groups. These networks are segmentally organised in organisms across the animal kingdom. The precise role of neuromodulatory signalling molecules in the function, development and, particularly, the maintenance of these circuits is currently unresolved. This study investigates the effects of chronically altered signalling of two such molecules, tyramine and octopamine, two well established neuromodulators, in Drosophila larval locomotion. It shows that tyramine reduces crawling speed in larvae, whereas octopamine increases speed up to a physiological maximum. Changes in crawling speed are mediated by modulating stride duration, whilst stride length remains constant. These two neuromodulators also affect segmental muscle contraction and relaxation rates, indicative that the effects on crawling speed are likely to be at least partially due to modulatory effects on muscle physiology. However, this study also provides evidence that these neuromodulators also exert important modulatory effects in the larval central nervous system and thereby alter activity of individual motor neurons. Imaging studies show that octopamine and/or tyramine are likely to be released in close spatial proximity of motor neurons, which are functionally important in larval crawling. Although single motor neurons that form part of CPG networks involved in movement are affected in their function and output, the output of entire network does not seem affected. This suggests a compensatory mechanism, which is able to monitor and maintain the function and output of entire networks.

Keyword(s)

Drosophila, CNS, neuromodulators, octopamine, tyramine, central pattern generator, locomotion

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