Do spinal circuits still require gating of sensory information by presynaptic inhibition after spinal cord injury?

Lalonde, Nicolas R; Bui, Tuan V.

doi:10.1016/j.cophys.2020.10.001

Cited by 12 publications

(19 citation statements)

References 64 publications

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“…A minimally trisynaptic circuit is classically known to depolarize afferents via GABA axo neurons. This circuit involves sensory afferents activating excitatory intermediary neurons (glutamatergic) that in turn activate GABA axo neurons that return to innervate sensory axons 13, 128 . Even though GABA axo neurons are small 5 this circuit influences afferents over widespread regions of the spinal cord 15 .…”

Section: Supplementary Informationmentioning

confidence: 99%

GABA facilitates spike propagation through branch points of sensory axons in the spinal cord

Hari

Lucas‐Osma

Metz

et al. 2021

Preprint

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SUMMARYGABA is an inhibitory neurotransmitter that produces both postsynaptic and presynaptic inhibition. We describe here an opposing excitatory action of GABA that facilitates spike transmission at nodes of Ranvier in myelinated sensory axons in the spinal cord. This nodal facilitation results from axonal GABAA receptors that depolarize nodes toward threshold, enabling spike propagation past the many branch points that otherwise fail, as observed in spinal cords isolated from mice or rats. Activation of GABAergic neurons, either directly with optogenetics or indirectly with cutaneous stimulation, caused nodal facilitation that increased sensory transmission to motoneurons without postsynaptically exciting motoneurons. This increased transmission with optogenetic or cutaneous stimulation also occurred in awake mice and humans. Optogenetic inhibition of GABAergic neurons decreased sensory transmission, implying that axonal conduction relies on GABA. The concept of nodal facilitation likely generalizes to other large axons in the CNS, enabling recruitment of selective branches and functional pathways.

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Section: Supplementary Informationmentioning

confidence: 99%

GABA facilitates spike propagation through branch points of sensory axons in the spinal cord

Hari

Lucas‐Osma

Metz

et al. 2021

Preprint

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“…Thus, the drive from the CST during volitional movements and the coincident activation of movement-related proprioceptive and cutaneous inputs may help to secure propagation of action potentials in sensory axons toward both the brain and spinal cord to facilitate the use of this sensory information in movement generation and control. Such regulation of afferent conduction may be affected by brain or spinal cord injury given the known changes to GABAergic networks following these insults (Faist et al, 1994;Tillakaratne et al, 2000;Kapitza et al, 2012;Mende et al, 2016;Khalki et al, 2018;Lalonde & Bui, 2021). Perhaps some of the problems with movement control and development of spasticity from injury may be produced by alterations in GABAergic control of nodal facilitation in afferents, a topic we are currently exploring.…”

Section: Functional Implicationsmentioning

confidence: 99%

“…The copyright holder for this preprint (which this version posted April 21, 2021. ; https://doi.org/10. 1101/2021…”

Section: Functional Implicationsmentioning

confidence: 99%

“…Peripheral sensory pathways in the spinal cord regulate the transmission of action potentials in other sensory axons through a network of interneurons that release gammaaminobutyric-acid (GABA) onto these axons. Specifically proprioceptive, cutaneous or pain afferents activate excitatory glutamatergic interneurons, which in turn synapse onto specialized GABAergic interneurons (termed GABA axo neurons; GAD2+) with axo-axonic contacts onto other afferents, forming the classic tri-synaptic pathway described in (Jankowska et al, 1981;Alvarez, 1998;Lalonde & Bui, 2021). The activation of GABA A receptors on these sensory axons produces a local depolarization of the afferent due to an outward flow of chloride ions (Gallagher et al, 1978) [also reviewed in (Rudomin & Schmidt, 1999;Willis, 1999)].…”

Section: Introductionmentioning

confidence: 99%

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Facilitation of sensory axon conduction to motoneurons during cortical or sensory evoked primary afferent depolarization (PAD) in humans

Metz

Concha-Matos

et al. 2021

Preprint

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Sensory and cortical pathways activate GABAergic interneurons with axo-axonic connections onto proprioceptive (Ia) afferents that depolarize these afferents (termed primary afferent depolarization, PAD). In rodents sensory-evoked PAD is produced by GABAA receptors at nodes of Ranvier in Ia-afferents, rather than at presynaptic terminals, and facilitates action potential propagation to motoneurons by preventing branch point failures, rather than causing presynaptic inhibition. Here we examined if PAD likewise facilitates the Ia-afferent mediated H-reflex in humans by evoking PAD with both sensory and corticospinal tract (CST) stimulation. H-reflexes in several lower limb muscles were facilitated by prior conditioning from low-threshold proprioceptive, cutaneous or CST pathways, with a similar time course (~200 ms) to the PAD measured in rodent Ia-afferents. Long trains of repeated cutaneous or proprioceptive afferent stimulation produced long-lasting facilitation of the H-reflex for up to 2 minutes, consistent with the tonic depolarization of rodent Ia-afferents mediated by nodal α5-GABAA receptors for similar stimulation trains. Facilitation of the conditioned H-reflexes was not mediated by direct facilitation of the motoneurons because isolated stimulation of sensory or CST pathways did not modulate the firing rate of tonically activated motor units in tested muscles. Furthermore, cutaneous conditioning increased the firing probability of a single motor unit during the H-reflex without increasing its firing rate at this time, indicating that the underlying excitatory postsynaptic potential (EPSP) was more probable, but not larger. These results are consistent with sensory and CST pathways activating nodal GABAA receptors that reduce intermittent failure of action potentials propagating into Ia-afferent branches.

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“…The gating of sensory feedback to spinal circuits is an important spinal mechanism for controlling smooth and coordinated movement (Fink et al, 2014;Koch et al, 2017). One of these gating mechanisms is presynaptic inhibition through axoaxonic GABAergic innervation of the central terminals of sensory afferents (Eccles et al, 1962;Rudomin, 2009;Lalonde and Bui, 2021). Presynaptic inhibition of primary afferents contacting MNs is evident only after the 1st week of postnatal development (Betley et al, 2009;Sonner and Ladle, 2013).…”

Section: Introductionmentioning

confidence: 99%

Changes in Sensorimotor Connectivity to dI3 Interneurons in Relation to the Postnatal Maturation of Grasping

Laliberté

Farah

Steiner

et al. 2022

Front. Neural Circuits

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Primitive reflexes are evident shortly after birth. Many of these reflexes disappear during postnatal development as part of the maturation of motor control. This study investigates the changes of connectivity related to sensory integration by spinal dI3 interneurons during the time in which the palmar grasp reflex gradually disappears in postnatal mice pups. Our results reveal an increase in GAD65/67-labeled terminals to perisomatic Vglut1-labeled sensory inputs contacting cervical and lumbar dI3 interneurons between postnatal day 3 and day 25. In contrast, there were no changes in the number of perisomatic Vglut1-labeled sensory inputs to lumbar and cervical dI3 interneurons other than a decrease between postnatal day 15 and day 25. Changes in postsynaptic GAD65/67-labeled inputs to dI3 interneurons were inconsistent with a role in the sustained loss of the grasp reflex. These results suggest a possible link between the maturation of hand grasp during postnatal development and increased presynaptic inhibition of sensory inputs to dI3 interneurons.

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Do spinal circuits still require gating of sensory information by presynaptic inhibition after spinal cord injury?

Cited by 12 publications

References 64 publications

GABA facilitates spike propagation through branch points of sensory axons in the spinal cord

GABA facilitates spike propagation through branch points of sensory axons in the spinal cord

Facilitation of sensory axon conduction to motoneurons during cortical or sensory evoked primary afferent depolarization (PAD) in humans

Changes in Sensorimotor Connectivity to dI3 Interneurons in Relation to the Postnatal Maturation of Grasping

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