Opposing Aminergic Modulation of Distinct Spinal Locomotor Circuits and Their Functional Coupling during Amphibian Metamorphosis

Abstract

The biogenic amines serotonin (5-HT) and noradrenaline (NA) are well known modulators of central pattern-generating networks responsible for vertebrate locomotion. Here we have explored monoaminergic modulation of the spinal circuits that generate two distinct modes of locomotion in the metamorphosing frog Xenopus laevis. At metamorphic climax when propulsion is achieved by undulatory larval tail movements and/or by kicking of the newly developed adult hindlimbs, the underlying motor networks remain spontaneously active in vitro, producing either separate fast axial and slow appendicular rhythms or a single combined rhythm that drives coordinated tail-based and limb-based swimming in vivo. In isolated spinal cords already expressing distinct axial and limb rhythms, bath-applied 5-HT induced coupled network activity through an opposite slowing of axial rhythmicity (by increasing motoneuron burst and cycle durations) and an acceleration of limb rhythmicity (by decreasing burst and cycle durations). In contrast, in preparations spontaneously expressing coordinated fictive locomotion, exogenous NA caused a dissociation of spinal activity into separate faster axial and slower appendicular rhythms by decreasing and increasing burst and cycle durations, respectively. Moreover, in preparations from premetamorphic and postmetamorphic animals that express exclusively axial-based or limb-based locomotion, 5-HT and NA modified the developmentally independent rhythms in a similar manner to the amines' opposing effects on the coexisting circuits at metamorphic climax. Thus, by exerting differential modulatory actions on one network that are opposite to their influences on a second adjacent circuit, these two amines are able to precisely regulate the functional relationship between different rhythmogenic networks in a developing vertebrate's spinal cord.

Serotonergic Modulation of Locomotion in Zebrafish—Endogenous Release and Synaptic Mechanisms

“…In embryos, 5-HT only affects the burst duration without change in the frequency (Sillar et al, 1992), while in premetamorphic tadpoles it decreases the frequency (Rauscent et al, 2009). The mechanisms responsible for the change in the actions of 5-HT during development are not yet clear.…”

Adaptive plasticity of spino-extraocular motor coupling during locomotion in metamorphosing Xenopus laevis

“…There was also evidence for direct functional interactions between the spinal locomotor CPGs themselves (see also Combes et al, 2004;Rauscent et al, 2009), as indicated by the axial VR burst-timed modulation of both left and right Ext nerve burst discharge, and the reciprocal augmentation of axial burst amplitudes during each Ext burst (Fig. 4).…”

“…2B). After isolation in vitro, the brainstem/spinal cord of such animals during this transitional period continues to spontaneously generate the motor burst patterns that would normally drive axial or hindlimb muscle contractions underlying the two locomotor modes in vivo (Combes et al, 2004;Beyeler et al, 2008;Rauscent et al, 2009). As seen in the extracellular recordings of Fig.…”

“…For example, when both CPG networks are co-active at metamorphic climax, the efference copy drive may originate from either CPG, or both, and to varying degrees from one preparation of the 'same' visually identified developmental stage to another. Moreover, because the two CPGs continue to interact functionally as metamorphosis progresses (Rauscent et al, 2009), one network's influence on the extraocular motor centers may be exerted directly by its ascending spinoextraocular motor pathways, and/or mediated indirectly via a local influence on the other neighboring CPG and its own ascending pathways. As climax approaches and appendicular movement gradually supersedes undulatory propulsion, the effective spinoextraocular motor coupling becomes increasingly homolateral, eventually leading to MR motoneurons being driven exclusively to produce bilaterally synchronous bursts in time with hindlimb Ext motor bursts prior to tail resorption.…”

Convergent neuromodulation onto a network neuron can have divergent effects at the network level

“…Previous studies have proposed that different neuromodulators which activate the same ionic current or modify similar synaptic properties within a network can produce distinct network outputs by targeting distinct sets of neuron types (Swensen and Marder, 2001; Marder and Thirumalai, 2002; Rauscent et al, 2009; Calabrese et al, 2011). From this perspective, there appears to be little advantage for distinct neuromodulators employing convergent actions on the same voltage-gated current in the same neuron.…”