Primary Afferent Terminals Acting as Excitatory Interneurons Contribute to Spontaneous Motor Activities in the Immature Spinal Cord

Bos, Rémi; Brocard, Frédéric; Vinay, Laurent

doi:10.1523/jneurosci.0068-11.2011

Cited by 24 publications

(38 citation statements)

References 35 publications

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“…When PAD is large enough to reach firing threshold, it triggers DR discharges that are antidromically conducted toward the periphery, the DRRs (Willis 1999). The present experiments showing that DR discharges are signifi- cantly reduced in the presence of low concentrations of bumetanide (20 M) are consistent with the notion that NKCC1 cotransporters play a key role in maintaining a higher than equilibrium [Cl Ϫ ] i in primary afferent terminals and in the subsequent GABA A receptor-mediated PAD (see also Bos et al 2011). The fact that residual DR discharges persist in the presence of bumetanide indicates that either the concentration used was not sufficient to block all NKCC1 cotransporters or that another Cl Ϫ uptake mechanism (e.g., anion exchanger) might be involved.…”

Section: Discussionsupporting

confidence: 90%

“…As shown in Fig. 4, B2 and C), bumetanide (20 M) significantly reduced the occurrence of spontaneous discharges both in control ACSF (not shown, P Ͻ 0.01, Wilcoxon test, n ϭ 8; see also Bos et al 2011) and in the presence of DL-BHB (Fig. 4, B2, top and C, P Ͻ 0.05, one-way ANOVA, Tukey posttest, n ϭ 4) or lactate (Fig.…”

Section: Supplementing the Artificial Csf With Dl-␤-hydroxybutirate supporting

confidence: 54%

“…4A, rectified traces). DR discharges are mediated by activation of GABA A receptors (Bos et al 2011;Fellippa-Marques et al 2000). The two ESs DL-BHB (n ϭ 4) and lactate (n ϭ 4) altered neither the bursts (area: Fig.…”

Section: Supplementing the Artificial Csf With Dl-␤-hydroxybutirate mentioning

confidence: 96%

“…2) Spontaneous and evoked dorsal root (DR) discharges. The latter are elicited by electrical stimulation of an adjacent DR and are known as "dorsal root reflex" (Bos et al 2011;FellippaMarques et al 2000;Vinay et al 1999). They result from GABA A receptor-mediated primary afferent depolarizations reaching firing threshold, and therefore rely on the higher than equilibrium [Cl Ϫ ] i in primary afferent terminals, which is maintained by NKCC1 cotransporters (Alvarez-Leefmans et al 1988).…”

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confidence: 99%

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Glucose is an adequate energy substrate for the depolarizing action of GABA and glycine in the neonatal rat spinal cord in vitro

Bos

Vinay

2012

Journal of Neurophysiology

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In vitro studies have repeatedly demonstrated that the neurotransmitters γ-aminobutyric acid (GABA) and glycine depolarize immature neurons in many areas of the CNS, including the spinal cord. This widely accepted phenomenon was recently challenged by experiments showing that the depolarizing action of GABA on neonatal hippocampus and neocortex in vitro was prevented by adding energy substrates (ES), such as the ketone body metabolite dl-β-hydroxybutyric acid (DL-BHB), lactate, or pyruvate to the artificial cerebrospinal fluid (ACSF). It was suggested that GABA-induced depolarizations in vitro might be an artifact due to inadequate energy supply when glucose is the sole energy source, consistent with the energy metabolism of neonatal rat brain being largely dependent on ESs other than glucose. Here we examined the effects of these ESs (DL-BHB, lactate, pyruvate) on inhibitory postsynaptic potentials (IPSPs) recorded from neonatal rat lumbar spinal cord motoneurons (MNs), in vitro. We report that supplementing the ACSF with physiologic concentrations of DL-BHB, lactate, or pyruvate does not alter the reversal potential of IPSPs (E(IPSP)). Only high concentrations of pyruvate hyperpolarized E(IPSP). In addition, the depolarizing action of GABA on primary afferent terminals was not affected by supplementing the ACSF with ES at physiologic concentrations. We conclude that depolarizing IPSPs in immature MNs and the primary afferent depolarizations are not caused by inadequate energy supply. Glucose at its standard concentration appears to be an adequate ES for the neonatal spinal cord in vitro.

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Section: Discussionsupporting

confidence: 90%

Section: Supplementing the Artificial Csf With Dl-␤-hydroxybutirate supporting

confidence: 54%

Section: Supplementing the Artificial Csf With Dl-␤-hydroxybutirate mentioning

confidence: 96%

mentioning

confidence: 99%

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Glucose is an adequate energy substrate for the depolarizing action of GABA and glycine in the neonatal rat spinal cord in vitro

Bos

Vinay

2012

Journal of Neurophysiology

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“…6B). These smaller DRPs likely reflect primary afferent depolarizations generated centrally, as reported during fictive locomotion (Gossard et al 1989(Gossard et al , 1991 or spontaneous activity (Bos et al 2011), or generated by other afferent inputs, but the largest component is dependent on interaction with the contralateral plate. Thus, the responses to plate removal confirm an essential role of contralateral endpoint force in ipsilateral DRP generation.…”

Section: Perturbation Responsesmentioning

confidence: 89%

Stance-phase force on the opposite limb dictates swing-phase afferent presynaptic inhibition during locomotion

Hayes

Chang

Hochman

2012

Journal of Neurophysiology

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Presynaptic inhibition is a powerful mechanism for selectively and dynamically gating sensory inputs entering the spinal cord. We investigated how hindlimb mechanics influence presynaptic inhibition during locomotion using pioneering approaches in an in vitro spinal cord-hindlimb preparation. We recorded lumbar dorsal root potentials to measure primary afferent depolarization-mediated presynaptic inhibition and compared their dependence on hindlimb endpoint forces, motor output, and joint kinematics. We found that stance-phase force on the opposite limb, particularly at toe contact, strongly influenced the magnitude and timing of afferent presynaptic inhibition in the swinging limb. Presynaptic inhibition increased in proportion to opposite limb force, as well as locomotor frequency. This form of presynaptic inhibition binds the sensorimotor states of the two limbs, adjusting sensory inflow to the swing limb based on forces generated by the stance limb. Functionally, it may serve to adjust swing-phase sensory transmission based on locomotor task, speed, and step-to-step environmental perturbations.

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Central sensitization of dorsal root potentials and dorsal root reflexes: An in vitro study in the mouse spinal cord.

Vicente-Baz

López-García

Rivera-Arconada

2021

European Journal of Pain

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Background: Axo-axonic contacts onto central terminals of primary afferents modulate sensory inputs to the spinal cord. These contacts produce primary afferent depolarization (PAD), which serves as a mechanism for presynaptic inhibition, and also produce dorsal root reflexes (DRRs), which may regulate the excitability of peripheral terminals and second order neurons. We aimed to identify changes in these responses as a consequence of peripheral inflammation. Methods: In vitro spinal cord recordings of spontaneous activities in dorsal andventral roots were performed in control mice and following paw inflammation.We also used pharmacological assays to define the neurotransmitter systems implicated in such responses.Results: Paw inflammation increased the frequency and amplitude of spontaneous dorsal root depolarizations, the occurrence of DRRs and the amplitude of ventral roots depolarizations. PAD was classified in two different patterns based on their relation to ventral activity: time-locked and independent events. Both patterns increased in amplitude after paw inflammation, and independent events also increased in frequency. The circuits that were responsible for this activity implicated both glutamatergic and GABAergic transmission. Adrenergic modulation differentially affected both types of PAD, and this modulation changed after paw inflammation. Conclusions: Our findings suggest the existence of independent spinal circuits at the origin of PAD and DRRs. Inflammation modulates these circuits differentially, unveiling varied mechanisms of spinal sensitization. This in vitro approach provides an isolated model for the study of the mechanisms of central sensitization and for the performance of pharmacological assays with the purpose of identifying and testing novel antinociceptive targets.Significance: Spinal circuits modulate activity of primary afferents acting on central terminals. Under in vitro conditions, dorsal roots show spontaneous activity in the form of depolarizations and action potentials. Our findings are consistent with the existence of several independent generator circuits. Experimental paw inflammation reduced mechanical withdrawal threshold and significantly

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Primary Afferent Terminals Acting as Excitatory Interneurons Contribute to Spontaneous Motor Activities in the Immature Spinal Cord

Cited by 24 publications

References 35 publications

Glucose is an adequate energy substrate for the depolarizing action of GABA and glycine in the neonatal rat spinal cord in vitro

Glucose is an adequate energy substrate for the depolarizing action of GABA and glycine in the neonatal rat spinal cord in vitro

Stance-phase force on the opposite limb dictates swing-phase afferent presynaptic inhibition during locomotion

Central sensitization of dorsal root potentials and dorsal root reflexes: An in vitro study in the mouse spinal cord.

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