Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Vertebrate central pattern generators (CPGs) controlling locomotion contain neurons which provide the excitation that drives and maintains network rhythms. In a simple vertebrate, the developing Xenopus tadpole, we study the role of excitatory descending neurons with ipsilateral projecting axons (descending interneurons, dINs) in the control of swimming rhythms. In tadpoles with both intact central nervous system (CNS) and transections in the hindbrain, exciting some individual dINs in the caudal hindbrain region could start swimming repeatedly. Analyses indicated the recruitment of additional dINs immediately after such evoked dIN spiking and prior to swimming. Excitation of dINs can therefore be sufficient for the initiation of swimming. These "powerful" dINs all possessed both ascending and descending axons. However, their axonprojection lengths were not different from those of other excitatory dINs at similar locations. The dorsoventral position of dINs, as a population, significantly better matched that of cells marked by immunocytochemistry for the transcription factor CHX10 than other known neuron types in the ventralhindbrain and spinal cord. The comparison suggests that the excitatory interneurons including dINs are CHX10-positive, in agreement with CHX10 as a marker for excitatory neurons with ipsilateral projections in the spinal cord and brainstem of other vertebrates. Overall, our results further demonstrate the key importance of dINs in driving tadpole swimming rhythms.
Figure 1. Fictive swimming in a stage 37/38 tadpole and the neural circuit controlling swimming. (A) A side-view scale diagram of a developing tadpole at stage 37/38 with a top view of its central nervous system (CNS; gray) showing: m swimming myotomes; mb, midbrain; hb, hindbrain; sc, spinal cord; oc, otic capsule. Obex is where the hindbrainventricle closes and the landmark separating hb and sc. (B) Diagram showing most critical neuron populations and their synaptic connections in tadpole swimming central pattern generator (CPG). Each circle represents a neuron population. dIN, descending interneuron; cIN, commissural interneuron; MN, motoneuron. l.m.n. and r.m.n.: left and right motor nerve. (C) Typical activity of a right side dIN (r.dIN) and simultaneous left motor nerve (l.m.n) activity at the beginning of an episode of fictive swimming started by electrical stimulation to the headskin (arrow). *Indicates cIN inhibition.
Figure 2. Stimulating single dINs in tadpoles with hindbrain transections starts fictive swimming. (A1) Step current injection into a right side dIN (r.dIN1) initiates swimming-like rhythms in a tadpole with the left side spinal cord and caudal hindbrain removed (black trace shows a failed trial). (A2) Nine superimposed trials as in (A1) but on a faster time scale and with different injected current levels. (B1) Injecting depolarizing currents into a dIN in a tadpole with its right side hindbrain transected starts swimming. (B2) Seven successful trials are overlapped on a faster time scale. (C1) The rebound spiking of a right side dIN (r.dIN1) following the withdrawal of a hyperpolarizing current injection, which has stopped swimming for 1 s, re-starts swimming in a dual whole-cell recording. Dotted line indicates the resting membrane potential of l.dIN. (C2) Eight superimposed trials. Traces are lined up to the rising phase of the first dINspike in (B2,C2). Diagrams on the left show CNS as in Figure 1A with location of lesions and electrodes (same color-coded as the recording traces). Arrowheads indicate secondary EPSPs and spiking following the initial dIN spiking. Inset shows sequence of activity in the CPG (arrows) with resistor sign representing electrical coupling among ipsilateral dINs.
Figure 3. The features of swimming evoked by powerful dINs. (A) The beginning of a swimming episode started by tail skin stimulation (arrow). m.n. trace is rectified and threshold set to trigger burst events. Box area is stretched in the inset to show burst duration (t1), swimming frequency (1/t2) and duty cycle (t1/t2). (B) Swimming burst durations, frequencies and duty cycles for the first 50 cycles are lower in the episodes evoked by powerful dINs (red) than those started by skin stimulation (black). (C) The beginning of two swimming episodes started by a powerful dIN (traces before the initial spiking is off scale). Numbers in red and black mark dIN spikes and m.n. bursts used for calculating spiking/cycle periods, respectively. Both dIN and m.n. are recorded from the left side (diagram, l.dIN, l.m.n.). Arrowhead points at secondary dIN spiking. (D) The first, but not the second dIN spiking period is longer than swimming cycle period measured using m.n. bursts. Gray lines link measurements from the same recordings in (B,D). *Indicates p < 0.05.
Figure 4. Single spiking in a right side dIN (r.dIN1) in a tadpole with intact CNS reliably evokes fictive swimming (right inset drawing with arrows showing activity sequence). (A) In nine trials (two 10 ms and seven 1,000 ms current pulses), r.dIN1 spiking initiates swimming. (B) The distribution of r.dIN1 spike and EPSP time relative to the first spike after the first l.m.n. bursts (time 0, 94 trials for the histogram). The timing of three events (see the trace below for examples) are measured: initial r.dIN1 spike evoked by current injections (“a,†unfilled histogram); onset of the first EPSP (“b,†arrowhead, gray); 2nd r.dIN1 spike after m.n. bursts (“c,†filled). (C) Comparison between the time of the three events in (B). ***Indicates p < 0.001.
Figure 5. The location of powerful dIN somata and longitudinal axonal projections. (A) A diagram of the tadpolehindbrain and rostral spinal cord outline (dashed) showing the location of seven somata of the 10 powerful dINs in Figures 2, 3, 4 (red dots) relative to the mid/hindbrain border (0). The red lines above the sketch show the trajectories of their ascending and descending axons (dotted line indicates a broken axon). Arrowhead points at the obex. (B) Drawing of the axon branches and their trajectories in the CNS for dIN B marked in (A; also recording in Figure 2B). (C) Drawing of the axons and their trajectories for dIN C in (A; also recording in Figure 4). The area within the dashed box is photographed (inset). (D) Axon lengths of the seven powerful dINs are similar to those of other 12 dINs within the same region.
Figure 6. Comparing the location of CHX10 immuno-positive cells and neurons identified by their anatomy and physiology. (A) Photograph of CHX10 immuno-positive cells in the right side CNS of a stage 37/38 tadpole (image flipped). The hindbrain and rostral spinal cord is outlined by the white dashed line. Arrowhead marks obex. (B) Comparing the dorsoventral soma positions of identified neuron groups [red: dINs, dINrs; blue: ascending interneurons (aINs), cINs; green: MNs, number of neurons given next to names] to the CHX10 immuno-positive cells (brown). The bottom of the hindbrain/spinal cord is set as 0 μm in the dorsoventral dimension and the mid/hindbrain border is set as 0 μm in the longitudinal dimension. *Indicates significance at p < 0.05 and ** at p < 0.01.
Borodinsky,
Activity-dependent homeostatic specification of transmitter expression in embryonic neurons.
2004, Pubmed,
Xenbase
Borodinsky,
Activity-dependent homeostatic specification of transmitter expression in embryonic neurons.
2004,
Pubmed
,
Xenbase
Bouvier,
Descending Command Neurons in the Brainstem that Halt Locomotion.
2015,
Pubmed
Bretzner,
Lhx3-Chx10 reticulospinal neurons in locomotor circuits.
2013,
Pubmed
Brodfuehrer,
Initiation of swimming activity by trigger neurons in the leech subesophageal ganglion. II. Role of segmental swim-initiating interneurons.
1986,
Pubmed
Brownstone,
Strategies for delineating spinal locomotor rhythm-generating networks and the possible role of Hb9 interneurones in rhythmogenesis.
2008,
Pubmed
Buchanan,
Swimming rhythm generation in the caudal hindbrain of the lamprey.
2018,
Pubmed
Buhl,
Sensory initiation of a co-ordinated motor response: synaptic excitation underlying simple decision-making.
2015,
Pubmed
,
Xenbase
Buhl,
The role of a trigeminal sensory nucleus in the initiation of locomotion.
2012,
Pubmed
,
Xenbase
Caldeira,
Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.
2017,
Pubmed
Cooke,
Locomotor recovery after spinal cord lesions in the lamprey is associated with functional and ultrastructural changes below lesion sites.
2009,
Pubmed
Crone,
Genetic ablation of V2a ipsilateral interneurons disrupts left-right locomotor coordination in mammalian spinal cord.
2008,
Pubmed
Crone,
In mice lacking V2a interneurons, gait depends on speed of locomotion.
2009,
Pubmed
Dale,
Dual-component synaptic potentials in the lamprey mediated by excitatory amino acid receptors.
1986,
Pubmed
Dale,
Dual-component amino-acid-mediated synaptic potentials: excitatory drive for swimming in Xenopus embryos.
1985,
Pubmed
,
Xenbase
Dougherty,
Locomotor rhythm generation linked to the output of spinal shox2 excitatory interneurons.
2013,
Pubmed
Dubuc,
Initiation of locomotion in lampreys.
2008,
Pubmed
Edwards,
Fifty years of a command neuron: the neurobiology of escape behavior in the crayfish.
1999,
Pubmed
Eklöf-Ljunggren,
Origin of excitation underlying locomotion in the spinal circuit of zebrafish.
2012,
Pubmed
Gosgnach,
The role of genetically-defined interneurons in generating the mammalian locomotor rhythm.
2011,
Pubmed
Goulding,
Circuits controlling vertebrate locomotion: moving in a new direction.
2009,
Pubmed
Hayashi,
Graded Arrays of Spinal and Supraspinal V2a Interneuron Subtypes Underlie Forelimb and Hindlimb Motor Control.
2018,
Pubmed
Hinckley,
Locomotor-like rhythms in a genetically distinct cluster of interneurons in the mammalian spinal cord.
2005,
Pubmed
Huang,
Spinal projection neurons control turning behaviors in zebrafish.
2013,
Pubmed
Jordan,
Descending command systems for the initiation of locomotion in mammals.
2008,
Pubmed
Kiehn,
Decoding the organization of spinal circuits that control locomotion.
2016,
Pubmed
Kimura,
Hindbrain V2a neurons in the excitation of spinal locomotor circuits during zebrafish swimming.
2013,
Pubmed
Kimura,
alx, a zebrafish homolog of Chx10, marks ipsilateral descending excitatory interneurons that participate in the regulation of spinal locomotor circuits.
2006,
Pubmed
Koutsikou,
A simple decision to move in response to touch reveals basic sensory memory and mechanisms for variable response times.
2018,
Pubmed
,
Xenbase
Li,
Reconfiguration of a vertebrate motor network: specific neuron recruitment and context-dependent synaptic plasticity.
2007,
Pubmed
,
Xenbase
Li,
Primitive roles for inhibitory interneurons in developing frog spinal cord.
2004,
Pubmed
,
Xenbase
Li,
Glutamate and acetylcholine corelease at developing synapses.
2004,
Pubmed
,
Xenbase
Li,
Locomotor rhythm maintenance: electrical coupling among premotor excitatory interneurons in the brainstem and spinal cord of young Xenopus tadpoles.
2009,
Pubmed
,
Xenbase
Li,
The control of locomotor frequency by excitation and inhibition.
2012,
Pubmed
,
Xenbase
Li,
Persistent responses to brief stimuli: feedback excitation among brainstem neurons.
2006,
Pubmed
,
Xenbase
Ljunggren,
Optogenetic activation of excitatory premotor interneurons is sufficient to generate coordinated locomotor activity in larval zebrafish.
2014,
Pubmed
Lundfald,
Phenotype of V2-derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord.
2007,
Pubmed
Moult,
Fast silencing reveals a lost role for reciprocal inhibition in locomotion.
2013,
Pubmed
,
Xenbase
Pivetta,
Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin.
2014,
Pubmed
Roberts,
Simple mechanisms organise orientation of escape swimming in embryos and hatchling tadpoles of Xenopus laevis.
2000,
Pubmed
,
Xenbase
Roberts,
How neurons generate behavior in a hatchling amphibian tadpole: an outline.
2010,
Pubmed
,
Xenbase
Roberts,
A functional scaffold of CNS neurons for the vertebrates: the developing Xenopus laevis spinal cord.
2012,
Pubmed
,
Xenbase
Soffe,
Defining the excitatory neurons that drive the locomotor rhythm in a simple vertebrate: insights into the origin of reticulospinal control.
2009,
Pubmed
,
Xenbase
Song,
V2a interneuron diversity tailors spinal circuit organization to control the vigor of locomotor movements.
2018,
Pubmed
Wilson,
Conditional rhythmicity of ventral spinal interneurons defined by expression of the Hb9 homeodomain protein.
2005,
Pubmed
Zhang,
Short-term memory of motor network performance via activity-dependent potentiation of Na+/K+ pump function.
2012,
Pubmed
,
Xenbase
