Opposing modulatory effects of D1- and D2-like receptor activation on a spinal central pattern generator

2012 ◽  
Vol 107 (8) ◽  
pp. 2250-2259 ◽  
Author(s):  
S. Clemens ◽  
A. Belin-Rauscent ◽  
J. Simmers ◽  
D. Combes
Keyword(s):  
Spinal Cord ◽  
Central Pattern Generator ◽  
Sch 23390 ◽  
Receptor Activation ◽  
Pattern Generator ◽  
High Concentration ◽  
Bath Application ◽  
D1 Agonist ◽  
Rhythmic Behaviors

The role of dopamine in regulating spinal cord function is receiving increasing attention, but its actions on spinal motor networks responsible for rhythmic behaviors remain poorly understood. Here, we have explored the modulatory influence of dopamine on locomotory central pattern generator (CPG) circuitry in the spinal cord of premetamorphic Xenopus laevis tadpoles. Bath application of exogenous dopamine to isolated brain stem-spinal cords exerted divergent dose-dependent effects on spontaneous episodic patterns of locomotory-related activity recorded extracellularly from spinal ventral roots. At low concentration (2 μM), dopamine reduced the occurrence of bursts and fictive swim episodes and increased episode cycle periods. In contrast, at high concentration (50 μM) dopamine reversed its actions on fictive swimming, now increasing both burst and swim episode occurrences while reducing episode periods. The low-dopamine effects were mimicked by the D2-like receptor agonists bromocriptine and quinpirole, whereas the D1-like receptor agonist SKF 38393 reproduced the effects of high dopamine. Furthermore, the motor response to the D1-like antagonist SCH 23390 resembled that to the D2 agonists, whereas the D2-like antagonist raclopride mimicked the effects of the D1 agonist. Together, these findings indicate that dopamine plays an important role in modulating spinal locomotor activity. Moreover, the transmitter's opposing influences on the same target CPG are likely to be accomplished by a specific, concentration-dependent recruitment of independent D2- and D1-like receptor signaling pathways that differentially mediate inhibitory and excitatory actions.

scholarly journals Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Melanie Falgairolle ◽  
Joshua G Puhl ◽  
Avinash Pujala ◽  
Wenfang Liu ◽  
Michael J O’Donovan
Keyword(s):  
Spinal Cord ◽  
Transcription Factor ◽  
Gap Junctions ◽  
Central Pattern Generator ◽  
Choline Acetyltransferase ◽  
Pattern Generator ◽  
Drug Induced ◽  
Partial Blockade ◽  
Lumbar Cord

Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase neurons (ChAT+) or Arch in LIM-homeodomain transcription factor Isl1+ neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT+ or Isl1+ neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm. When the light was turned off motoneuron firing and locomotor frequency both transiently increased. These effects were not due to cholinergic neurotransmission, persisted during partial blockade of gap junctions and were mediated, in part, by AMPAergic transmission. In spinal cords expressing ChR2, illumination increased motoneuron discharge and transiently accelerated the rhythm. We conclude that motoneurons provide feedback to the central pattern generator (CPG) during drug-induced locomotor-like activity.

Neural mechanisms of intersegmental coordination in lamprey: local excitability changes modify the phase coupling along the spinal cord

1992 ◽  
Vol 67 (2) ◽  
pp. 373-388 ◽  
Author(s):  
T. Matsushima ◽  
S. Grillner
Keyword(s):  
Spinal Cord ◽  
Forward Direction ◽  
Neural Mechanisms ◽  
Cycle Duration ◽  
Phase Lag ◽  
High Concentration ◽  
Caudal Portion ◽  
Bath Application ◽  
Ventral Roots

1. To elucidate the neural mechanisms responsible for coordinating undulatory locomotor movements, the intersegmental phase lag was analyzed from ventral roots along the spinal cord during fictive swimming. It was induced by bath application of N-methyl-D-aspartate (NMDA) in in vitro preparations of lamprey spinal cord, while the excitability of different segments were modified. The phase lag between consecutive segments during normal forward swimming is 1% of the cycle duration in a broad range of values. Rostral segments are activated before more caudal ones. 2. Under control conditions, whole preparations (12-24 segment long; n = 22) were perfused with NMDA solutions of the same concentration (100-150 microM). The intersegmental phase lag values varied in a continuous range with a single peak around a median value of forward +0.74% per segment (range: forward +2.23% to backward -0.97%). 3. To examine whether excitability differences along the spinal cord could modify the intersegmental phase lag, different levels of excitatory amino acids (NMDA) were applied to spinal cord preparations positioned in a partitioned chamber. Different portions of the cord could be perfused separately by NMDA solutions of different concentrations (50-150 microM). If rostral segments were perfused with the higher NMDA solution, the lag was inevitably in the forward direction. Conversely, if the caudal portion was perfused with the higher NMDA solution, caudally located ventral roots became activated before the rostral ventral roots in a caudorostral succession, thus reversing the direction of the fictive swimming wave to propagate as during backward swimming. If the middle portion was perfused by the highest NMDA solution, this portion instead became leading, and the activity propagated from this point in both the rostral and the caudal directions. The portion located in the pool with highest NMDA concentration always gave rise to a "leading" segment. 4. When a portion of the preparation was perfused with an NMDA solution of a high concentration (75-150 microM), the cycle duration was close to that recorded when the whole preparation was perfused with the same high NMDA solution. The ensemble cycle duration is, therefore, largely determined by the leading segment. 5. The phase lag changes were not restricted to the region around the barrier separating pools with different NMDA solutions.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Output variability across animals and levels in a motor system

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Angela Wenning ◽  
Brian J Norris ◽  
Cengiz Günay ◽  
Daniel Kueh ◽  
Ronald L Calabrese
Keyword(s):  
Life History ◽  
Central Pattern Generator ◽  
Motor Neurons ◽  
Motor System ◽  
Motor Pattern ◽  
Pattern Generator ◽  
Phase Relations ◽  
The Other ◽  
Output Variability ◽  
Rhythmic Behaviors

Rhythmic behaviors vary across individuals. We investigated the sources of this output variability across a motor system, from the central pattern generator (CPG) to the motor plant. In the bilaterally symmetric leech heartbeat system, the CPG orchestrates two coordinations in the bilateral hearts with different intersegmental phase relations (Δϕ) and periodic side-to-side switches. Population variability is large. We show that the system is precise within a coordination, that differences in repetitions of a coordination contribute little to population output variability, but that differences between bilaterally homologous cells may contribute to some of this variability. Nevertheless, much output variability is likely associated with genetic and life history differences among individuals. Variability of Δϕ were coordination-specific: similar at all levels in one, but significantly lower for the motor pattern than the CPG pattern in the other. Mechanisms that transform CPG output to motor neurons may limit output variability in the motor pattern.

Cholinergic contribution to excitation in a spinal locomotor central pattern generator in Xenopus embryos

1995 ◽  
Vol 73 (3) ◽  
pp. 1013-1019 ◽  
Author(s):  
R. Perrins ◽  
A. Roberts
Keyword(s):  
Spinal Cord ◽  
Central Pattern Generator ◽  
Excitatory Amino Acid ◽  
Pattern Generator ◽  
Excitatory Input ◽  
Intracellular Recordings ◽  
Electrical Excitation ◽  
Spinal Interneurons ◽  
Xenopus Embryos ◽  
Spike Firing

1. We have investigated whether in Xenopus embryos, spinal interneurons of the central pattern generator (CPG) receive cholinergic or electrical excitatory input during swimming. The functions of cholinergic excitation during swimming were also investigated. 2. Intracellular recordings were made from rhythmically active presumed premotor interneurons in the dorsal third of the spinal cord. After locally blocking inhibitory potentials with 2 microM strychnine and 40 microM bicuculline, the reliability of spike firing and the amplitude of fast, on-cycle, excitatory postsynaptic potentials (EPSPs) underlying the single on-cycle spikes were measured during fictive swimming. 3. The nicotinic antagonists d-tubocurarine and dihydro-beta-erythroidine (DH beta E, both 10 microM) reversibly reduced the reliability of the spike firing during swimming and reduced the amplitude of the on-cycle EPSP by 16%. DH beta E also reduced the EPSP amplitude in spinalized embryos by 22%. These results indicate that interneurons receive rhythmic cholinergic excitation from a source within the spinal cord. 4. Combined applications of nicotinic and excitatory amino acid (EAA) antagonists or cadmium (Cd2+, 100-200 microM) resulted in complete block of the fast EPSP, suggesting that interneurons do not receive electrical excitation. 5. The nicotinic antagonists mecamylamine and d-tubocurarine (both 5 microM) reduced the duration of episodes of fictive swimming recorded from the ventral roots, in spinal embryos. When applied in the middle of a long episode, d-tubocurarine decreased the swimming frequency, ruling out an effect on the initiation pathway. The cholinesterase inhibitor eserine (10 microM) increased the duration of swimming episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

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