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A circuit mechanism for the propagation of waves of muscle contraction in Drosophila.

Fushiki A, Zwart MF, Kohsaka H, Fetter RD, Cardona A, Nose A - Elife (2016)

Bottom Line: We found an intersegmental chain of synaptically connected neurons, alternating excitatory and inhibitory, necessary for wave propagation and active in phase with the wave.The inhibitory neurons (GDL) are necessary for both forward and backward locomotion, suggestive of different yet coupled central pattern generators, and its inhibition is necessary for wave propagation.The circuit structure and functional imaging indicated that the commands to contract one segment promote the relaxation of the next segment, revealing a mechanism for wave propagation in peristaltic locomotion.

View Article: PubMed Central - PubMed

Affiliation: Department of Complexity Science and Engineering, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.

ABSTRACT
Animals move by adaptively coordinating the sequential activation of muscles. The circuit mechanisms underlying coordinated locomotion are poorly understood. Here, we report on a novel circuit for the propagation of waves of muscle contraction, using the peristaltic locomotion of Drosophila larvae as a model system. We found an intersegmental chain of synaptically connected neurons, alternating excitatory and inhibitory, necessary for wave propagation and active in phase with the wave. The excitatory neurons (A27h) are premotor and necessary only for forward locomotion, and are modulated by stretch receptors and descending inputs. The inhibitory neurons (GDL) are necessary for both forward and backward locomotion, suggestive of different yet coupled central pattern generators, and its inhibition is necessary for wave propagation. The circuit structure and functional imaging indicated that the commands to contract one segment promote the relaxation of the next segment, revealing a mechanism for wave propagation in peristaltic locomotion.

No MeSH data available.


Related in: MedlinePlus

Synaptic relations of GDL and A27h with known larval interneurons.(A) One of the PMSI neurons (glutamatergic neurons involved in the speed regulation; [Kohsaka et al., 2014]), named A02j, relates GDLs to each other across abdominal segments. In particular, A02j synapses onto the GDLs of the two segments anterior to its own segment, potentially starting the excitatory drive over GDLs to promote the relaxation of segments anterior to the muscle contraction wave. Additionally, A02j synapses directly onto some motor neurons of the segments anterior to its own segment (not shown), with potentially an inhibitory effect as shown in (Kohsaka et al., 2014). Interestingly, A02j in one segment might promote the disinhibition of its anterior homologs, given than GDL, a GABAergic neuron, synapses onto a segment-local putatively GABAergic neuron (A31d; similar morphology and belonging to the same lineage as the GABAergic neurons A31b and A31k [Schneider-Mizell et al., in press]). (B) The GDL-A27h circuit interacts with neurons known to affect the speed of locomotion (PMSIs and GVLIs). A02d is a PMSI neuron (Kohsaka et al., 2014) that receives inputs from GDL and in turn synapses onto the A08a neuron (a GVLI; [Itakura et al., 2015]). A08a, in turn, synapses onto two putatively GABAergic neurons (A31d and A31x). This circuit suggests that GDL prevents A02d from driving A08a, which could potentially underlie the observed activation pattern of A08a, which is active two segments posterior to the forward-moving peristaltic wave (Itakura et al., 2015). We did not observe synapses between A08a and motor neurons. Furthermore, GDL might provide inhibition ipsilaterally to the contralaterally projecting, Eve-Skipped+ neuron A08e3, which is necessary for maintaining bilaterally symmetric muscle contraction amplitude (Heckscher et al., 2015). This suggests a role for GDL in the regulation of posture adjustment, and therefore a close relationship between the circuits for wave propagation and the circuits for ensuring symmetrical muscle contractions in forward locomotion. (C) The connectivity matrix between proprioceptive sensory neurons and A02d (one of the PMSIs), A08a (GVLIs), and A08e3 (one of the Even-Skipped+ neurons).DOI:http://dx.doi.org/10.7554/eLife.13253.027
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fig8s2: Synaptic relations of GDL and A27h with known larval interneurons.(A) One of the PMSI neurons (glutamatergic neurons involved in the speed regulation; [Kohsaka et al., 2014]), named A02j, relates GDLs to each other across abdominal segments. In particular, A02j synapses onto the GDLs of the two segments anterior to its own segment, potentially starting the excitatory drive over GDLs to promote the relaxation of segments anterior to the muscle contraction wave. Additionally, A02j synapses directly onto some motor neurons of the segments anterior to its own segment (not shown), with potentially an inhibitory effect as shown in (Kohsaka et al., 2014). Interestingly, A02j in one segment might promote the disinhibition of its anterior homologs, given than GDL, a GABAergic neuron, synapses onto a segment-local putatively GABAergic neuron (A31d; similar morphology and belonging to the same lineage as the GABAergic neurons A31b and A31k [Schneider-Mizell et al., in press]). (B) The GDL-A27h circuit interacts with neurons known to affect the speed of locomotion (PMSIs and GVLIs). A02d is a PMSI neuron (Kohsaka et al., 2014) that receives inputs from GDL and in turn synapses onto the A08a neuron (a GVLI; [Itakura et al., 2015]). A08a, in turn, synapses onto two putatively GABAergic neurons (A31d and A31x). This circuit suggests that GDL prevents A02d from driving A08a, which could potentially underlie the observed activation pattern of A08a, which is active two segments posterior to the forward-moving peristaltic wave (Itakura et al., 2015). We did not observe synapses between A08a and motor neurons. Furthermore, GDL might provide inhibition ipsilaterally to the contralaterally projecting, Eve-Skipped+ neuron A08e3, which is necessary for maintaining bilaterally symmetric muscle contraction amplitude (Heckscher et al., 2015). This suggests a role for GDL in the regulation of posture adjustment, and therefore a close relationship between the circuits for wave propagation and the circuits for ensuring symmetrical muscle contractions in forward locomotion. (C) The connectivity matrix between proprioceptive sensory neurons and A02d (one of the PMSIs), A08a (GVLIs), and A08e3 (one of the Even-Skipped+ neurons).DOI:http://dx.doi.org/10.7554/eLife.13253.027

Mentions: We found that the excitatory neuron (A27h) is premotor, directly synapsing onto motor neurons of its own segment only and that control both dorsal and ventral longitudinal muscles. This suggests an explanation for the observation that in forward crawling, dorsal and ventral longitudinal muscles contract simultaneously (Heckscher et al., 2012). In backward peristalsis, however, a phase gap has been observed in the timing of dorsal and ventral muscle contraction (Heckscher et al., 2012). This decoupling could require a more complex circuit structure for backward wave propagation, and therefore suggests an explanation for the lack of an equivalent excitatory neuron in the circuit chain for backward peristalsis. We found, however, neurons postsynaptic to the inhibitory neuron (GDL) whose anatomy and position in the circuit suggest a role in backward peristalsis (Figure 8—figure supplement 1A). In contrast, the inhibitory neuron (GDL) itself does not synapse onto motor neurons, and therefore occupies a higher-order position in the circuit that allows its participation in both forward and backward wave propagation in peristalsis. Furthermore, the GDL axon targets the intermediate lateral neuropil, which is neither in the domain of motor neuron dendrites nor in the somatosensory domain, suggestive of a role higher-order motor coordination. Relevant for forward peristalsis, GDL disinhibits the excitation of its anterior homologs, by removing inhibition from a glutamatergic interneurons (A02j) implicated in the regulation of peristaltic speed (one of the PMSIs; [Kohsaka et al., 2014]). A02j is presynaptic to GDLs in anterior segments (Figure 4D and Figure 8—figure supplement 2A).


A circuit mechanism for the propagation of waves of muscle contraction in Drosophila.

Fushiki A, Zwart MF, Kohsaka H, Fetter RD, Cardona A, Nose A - Elife (2016)

Synaptic relations of GDL and A27h with known larval interneurons.(A) One of the PMSI neurons (glutamatergic neurons involved in the speed regulation; [Kohsaka et al., 2014]), named A02j, relates GDLs to each other across abdominal segments. In particular, A02j synapses onto the GDLs of the two segments anterior to its own segment, potentially starting the excitatory drive over GDLs to promote the relaxation of segments anterior to the muscle contraction wave. Additionally, A02j synapses directly onto some motor neurons of the segments anterior to its own segment (not shown), with potentially an inhibitory effect as shown in (Kohsaka et al., 2014). Interestingly, A02j in one segment might promote the disinhibition of its anterior homologs, given than GDL, a GABAergic neuron, synapses onto a segment-local putatively GABAergic neuron (A31d; similar morphology and belonging to the same lineage as the GABAergic neurons A31b and A31k [Schneider-Mizell et al., in press]). (B) The GDL-A27h circuit interacts with neurons known to affect the speed of locomotion (PMSIs and GVLIs). A02d is a PMSI neuron (Kohsaka et al., 2014) that receives inputs from GDL and in turn synapses onto the A08a neuron (a GVLI; [Itakura et al., 2015]). A08a, in turn, synapses onto two putatively GABAergic neurons (A31d and A31x). This circuit suggests that GDL prevents A02d from driving A08a, which could potentially underlie the observed activation pattern of A08a, which is active two segments posterior to the forward-moving peristaltic wave (Itakura et al., 2015). We did not observe synapses between A08a and motor neurons. Furthermore, GDL might provide inhibition ipsilaterally to the contralaterally projecting, Eve-Skipped+ neuron A08e3, which is necessary for maintaining bilaterally symmetric muscle contraction amplitude (Heckscher et al., 2015). This suggests a role for GDL in the regulation of posture adjustment, and therefore a close relationship between the circuits for wave propagation and the circuits for ensuring symmetrical muscle contractions in forward locomotion. (C) The connectivity matrix between proprioceptive sensory neurons and A02d (one of the PMSIs), A08a (GVLIs), and A08e3 (one of the Even-Skipped+ neurons).DOI:http://dx.doi.org/10.7554/eLife.13253.027
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Related In: Results  -  Collection

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fig8s2: Synaptic relations of GDL and A27h with known larval interneurons.(A) One of the PMSI neurons (glutamatergic neurons involved in the speed regulation; [Kohsaka et al., 2014]), named A02j, relates GDLs to each other across abdominal segments. In particular, A02j synapses onto the GDLs of the two segments anterior to its own segment, potentially starting the excitatory drive over GDLs to promote the relaxation of segments anterior to the muscle contraction wave. Additionally, A02j synapses directly onto some motor neurons of the segments anterior to its own segment (not shown), with potentially an inhibitory effect as shown in (Kohsaka et al., 2014). Interestingly, A02j in one segment might promote the disinhibition of its anterior homologs, given than GDL, a GABAergic neuron, synapses onto a segment-local putatively GABAergic neuron (A31d; similar morphology and belonging to the same lineage as the GABAergic neurons A31b and A31k [Schneider-Mizell et al., in press]). (B) The GDL-A27h circuit interacts with neurons known to affect the speed of locomotion (PMSIs and GVLIs). A02d is a PMSI neuron (Kohsaka et al., 2014) that receives inputs from GDL and in turn synapses onto the A08a neuron (a GVLI; [Itakura et al., 2015]). A08a, in turn, synapses onto two putatively GABAergic neurons (A31d and A31x). This circuit suggests that GDL prevents A02d from driving A08a, which could potentially underlie the observed activation pattern of A08a, which is active two segments posterior to the forward-moving peristaltic wave (Itakura et al., 2015). We did not observe synapses between A08a and motor neurons. Furthermore, GDL might provide inhibition ipsilaterally to the contralaterally projecting, Eve-Skipped+ neuron A08e3, which is necessary for maintaining bilaterally symmetric muscle contraction amplitude (Heckscher et al., 2015). This suggests a role for GDL in the regulation of posture adjustment, and therefore a close relationship between the circuits for wave propagation and the circuits for ensuring symmetrical muscle contractions in forward locomotion. (C) The connectivity matrix between proprioceptive sensory neurons and A02d (one of the PMSIs), A08a (GVLIs), and A08e3 (one of the Even-Skipped+ neurons).DOI:http://dx.doi.org/10.7554/eLife.13253.027
Mentions: We found that the excitatory neuron (A27h) is premotor, directly synapsing onto motor neurons of its own segment only and that control both dorsal and ventral longitudinal muscles. This suggests an explanation for the observation that in forward crawling, dorsal and ventral longitudinal muscles contract simultaneously (Heckscher et al., 2012). In backward peristalsis, however, a phase gap has been observed in the timing of dorsal and ventral muscle contraction (Heckscher et al., 2012). This decoupling could require a more complex circuit structure for backward wave propagation, and therefore suggests an explanation for the lack of an equivalent excitatory neuron in the circuit chain for backward peristalsis. We found, however, neurons postsynaptic to the inhibitory neuron (GDL) whose anatomy and position in the circuit suggest a role in backward peristalsis (Figure 8—figure supplement 1A). In contrast, the inhibitory neuron (GDL) itself does not synapse onto motor neurons, and therefore occupies a higher-order position in the circuit that allows its participation in both forward and backward wave propagation in peristalsis. Furthermore, the GDL axon targets the intermediate lateral neuropil, which is neither in the domain of motor neuron dendrites nor in the somatosensory domain, suggestive of a role higher-order motor coordination. Relevant for forward peristalsis, GDL disinhibits the excitation of its anterior homologs, by removing inhibition from a glutamatergic interneurons (A02j) implicated in the regulation of peristaltic speed (one of the PMSIs; [Kohsaka et al., 2014]). A02j is presynaptic to GDLs in anterior segments (Figure 4D and Figure 8—figure supplement 2A).

Bottom Line: We found an intersegmental chain of synaptically connected neurons, alternating excitatory and inhibitory, necessary for wave propagation and active in phase with the wave.The inhibitory neurons (GDL) are necessary for both forward and backward locomotion, suggestive of different yet coupled central pattern generators, and its inhibition is necessary for wave propagation.The circuit structure and functional imaging indicated that the commands to contract one segment promote the relaxation of the next segment, revealing a mechanism for wave propagation in peristaltic locomotion.

View Article: PubMed Central - PubMed

Affiliation: Department of Complexity Science and Engineering, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.

ABSTRACT
Animals move by adaptively coordinating the sequential activation of muscles. The circuit mechanisms underlying coordinated locomotion are poorly understood. Here, we report on a novel circuit for the propagation of waves of muscle contraction, using the peristaltic locomotion of Drosophila larvae as a model system. We found an intersegmental chain of synaptically connected neurons, alternating excitatory and inhibitory, necessary for wave propagation and active in phase with the wave. The excitatory neurons (A27h) are premotor and necessary only for forward locomotion, and are modulated by stretch receptors and descending inputs. The inhibitory neurons (GDL) are necessary for both forward and backward locomotion, suggestive of different yet coupled central pattern generators, and its inhibition is necessary for wave propagation. The circuit structure and functional imaging indicated that the commands to contract one segment promote the relaxation of the next segment, revealing a mechanism for wave propagation in peristaltic locomotion.

No MeSH data available.


Related in: MedlinePlus