Dopamine exerts activation-dependent modulation of spinal locomotor circuits in the neonatal mouse

2012 ◽  
Vol 108 (12) ◽  
pp. 3370-3381 ◽  
Author(s):  
Jennifer M. Humphreys ◽  
Patrick J. Whelan
Keyword(s):  
Spinal Cord ◽  
Feedback Loops ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Mouse Spinal Cord ◽  
Network Function ◽  
Renshaw Cell ◽  
Root Stimulation ◽  
Excitatory Drive

Monoamines can modulate the output of a variety of invertebrate and vertebrate networks, including the spinal cord networks that control walking. Here we examined the multiple changes in the output of locomotor networks induced by dopamine (DA). We found that DA can depress the activation of locomotor networks in the neonatal mouse spinal cord following ventral root stimulation. By examining disinhibited rhythms, where the Renshaw cell pathway was blocked, we found that DA depresses a putative recurrent excitatory pathway that projects onto rhythm-generating circuitry of the spinal cord. This depression was D2 but not D1 receptor dependent and was not due exclusively to depression of excitatory drive to motoneurons. Furthermore, the depression in excitation was not dependent on network activity. We next compared the modulatory effects of DA on network function by focusing on a serotonin and a N-methyl-dl-aspartate-evoked rhythm. In contrast to the depressive effects on a ventral root-evoked rhythm, we found that DA stabilized a drug-evoked rhythm, reduced the frequency of bursting, and increased amplitude. Overall, these data demonstrate that DA can potentiate network activity while at the same time reducing the gain of recurrent excitatory feedback loops from motoneurons onto the network.

scholarly journals Interactions between Dorsal and Ventral Root Stimulation on the Generation of Locomotor-Like Activity in the Neonatal Mouse Spinal Cord

eNeuro ◽  
2016 ◽  
Vol 3 (3) ◽  
pp. ENEURO.0101-16.2016 ◽  
Author(s):  
Avinash Pujala ◽  
Dvir Blivis ◽  
Michael J. O’Donovan
Keyword(s):  
Spinal Cord ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Mouse Spinal Cord ◽  
Root Stimulation

scholarly journals Excitatory Actions of Ventral Root Stimulation During Network Activity Generated by the Disinhibited Neonatal Mouse Spinal Cord

2009 ◽  
Vol 101 (6) ◽  
pp. 2995-3011 ◽  
Author(s):  
Agnes Bonnot ◽  
Nikolai Chub ◽  
Avinash Pujala ◽  
Michael J. O'Donovan
Keyword(s):  
Spinal Cord ◽  
Optical Activity ◽  
Metabotropic Glutamate Receptors ◽  
Ventral Root ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Cholinergic Antagonists ◽  
Type I ◽  
Mouse Spinal Cord ◽  
Spinal Network

To further understand the excitatory effects of motoneurons on spinal network function, we investigated the entrainment of disinhibited rhythms by ventral root (VR) stimulation in the neonatal mouse spinal cord. A brief train of stimuli applied to a VR triggered bursting reliably in 31/32 experiments. The same roots that entrained disinhibited bursting could also produce locomotor-like activity with a similar probability when the network was not disinhibited. The ability of VR stimulation to entrain the rhythm persisted in nicotinic and muscarinic cholinergic antagonists but was blocked by the AMPAR antagonist NBQX. Bath application of the type I mGluR1 receptor antagonist CPCCOEt reduced the ability of both dorsal root and VR stimulation to entrain the disinhibited rhythm and abolished the ability of either type of stimulation to evoke locomotor-like activity. Calcium imaging through the lateral aspect of the cord revealed that VR stimulation and spontaneously occurring bursts were accompanied by a wave of activity that originated ventrally and propagated dorsally. Imaging the cut transverse face of L5 revealed that the earliest VR-evoked optical activity began ventrolaterally. The optical activity accompanying spontaneous bursts could originate ventrolaterally, ventromedially, or throughout the mediolateral extent of the ventral horn or very occasionally dorsally. Collectively, our data indicate that VR stimulation can entrain disinhibited spinal network activity and trigger locomotor-like activity through a mechanism dependent on activation of both ionotropic and metabotropic glutamate receptors. The effects of entrainment appear to be mediated by a ventrolaterally located network that is also active during spontaneously occurring bursts.

Monoaminergic Establishment of Rostrocaudal Gradients of Rhythmicity in the Neonatal Mouse Spinal Cord

2005 ◽  
Vol 94 (2) ◽  
pp. 1554-1564 ◽  
Author(s):  
Kimberly J. Christie ◽  
Patrick J. Whelan
Keyword(s):  
Spinal Cord ◽  
Locomotor Activity ◽  
Spinal Cord Injuries ◽  
Neonatal Mouse ◽  
Network Activity ◽  
Neonatal Rats ◽  
Mouse Spinal Cord ◽  
Bath Application ◽  
Rats And Mice ◽  
Calcium Green

Bath application of monoamines is a potent method for evoking locomotor activity in neonatal rats and mice. Monoamines also promote functional recovery in adult animals with spinal cord injuries by activating spinal cord networks. However, the mechanisms of their actions on spinal networks are largely unknown. In this study, we tested the hypothesis that monoamines establish rostrocaudal gradients of rhythmicity in the thoracolumbar spinal cord. Isolated neonatal mouse spinal cord preparations (P0–P2) were used. To assay excitability of networks by monoamines, we evoked a disinhibited rhythm by bath application of picrotoxin and strychnine and recorded neurograms from several thoracolumbar ventral roots. We first established that rostral and caudal segments of the thoracolumbar spinal cord had equal excitability by completely transecting preparations at the L3 segmental level and recording the frequency of the disinhibited rhythm from both segments. Next we established that a majority of ventral interneurons retrogradely labeled by calcium green dextran were active during network activity. We then bath applied combinations of monoaminergic agonists [5-HT and dopamine (DA)] known to elicit locomotor activity. Our results show that monoamines establish rostrocaudal gradients of rhythmicity in the thoracolumbar spinal cord. This may be one mechanism by which combinations of monoaminergic compounds normally stably activate locomotor networks.

scholarly journals Orexinergic Modulation of Spinal Motor Activity in the Neonatal Mouse Spinal Cord

eNeuro ◽  
2018 ◽  
Vol 5 (5) ◽  
pp. ENEURO.0226-18.2018 ◽  
Author(s):  
Sukanya Biswabharati ◽  
Céline Jean-Xavier ◽  
Shane E. A. Eaton ◽  
Adam P. Lognon ◽  
Rhiannon Brett ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Activity ◽  
Neonatal Mouse ◽  
Mouse Spinal Cord ◽  
Spinal Motor ◽  
Spinal Motor Activity
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