RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait

Koch, Stephanie; Barrio, Marta García del; Dalet, Antoine; Gatto, Graziana; Günther, Thomas; Zhang, Jingming; Seidler, Barbara; Saur, Dieter; Schüle, Roland; Goulding, Martyn

doi:10.1016/j.neuron.2017.11.011

Cited by 92 publications

(133 citation statements)

References 86 publications

(130 reference statements)

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“…Here, inhibition exercises state-dependent control of sensory thresholds, for example suppressing nociceptive transmission during acute stress [23], and prevents sensorimotor reflexes from interfering with stable performance of motor acts such as reaching or locomotion [24,25]. Similarly, prepulse inhibition shares characteristics of both state- and task-dependent sensory gating.…”

Section: Discussionmentioning

confidence: 99%

Presynaptic Inhibition Selectively Gates Auditory Transmission to the Brainstem Startle Circuit

et al. 2018

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Filtering mechanisms prevent a continuous stream of sensory information from swamping perception, leading to diminished focal attention and cognitive processing. Mechanisms for sensory gating are commonly studied using prepulse inhibition, a paradigm that measures the regulated transmission of auditory information to the startle circuit; however, the underlying neuronal pathways are unresolved. Using large-scale calcium imaging, optogenetics, and laser ablations, we reveal a cluster of 30 morphologically identified neurons in zebrafish that suppress the transmission of auditory signals during prepulse inhibition. These neurons project to a key sensorimotor interface in the startle circuit-the termination zone of auditory afferents on the dendrite of a startle command neuron. Direct measurement of auditory nerve neurotransmitter release revealed selective presynaptic inhibition of sensory transmission to the startle circuit, sparing signaling to other brain regions. Our results provide the first cellular resolution circuit for prepulse inhibition in a vertebrate, revealing a central role for presynaptic gating of sensory information to a brainstem motor circuit.

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Section: Discussionmentioning

confidence: 99%

Presynaptic Inhibition Selectively Gates Auditory Transmission to the Brainstem Startle Circuit

et al. 2018

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“…More recently, last order GABAergic interneurons specifically involved in presynaptic inhibition have been genetically identified in rodent models (Fink et al, 2014;Koch et al, 2017) and presynaptic inhibitory mechanisms were shown to rely not only on GABAergic signaling, but also on other neurotransmitters, neuromodulators and receptors that also could contribute to our results (Kremer & Lev-Tov, 1998;Hochman et al, 2010;Lucas-Osma et al, 2018). Finally, mechanisms other than PAD are also likely to contribute to presynaptic inhibition of Ia afferents and possibly contribute to the PAD-independent presynaptic inhibition of the H-reflex in our experiments (Price et al, 1984;Stuart & Redman, 1992;Hultborn et al, 1996;Curtis et al, 1997;Garcia-Ramirez et al, 2014).…”

Section: Possible Mechanisms Contributing To the Reorganization Of Afmentioning

confidence: 99%

Direct evidence for decreased presynaptic inhibition evoked by PBSt group I muscle afferents after chronic SCI and recovery with step-training in the decerebrated rat

Caron

Bilchak

Côté

2020

Preprint

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Key point summary• Presynaptic inhibition is modulated by supraspinal centers and primary afferents in order to filter sensory information, adjust spinal reflex excitability, and ensure smooth movements.• After SCI, the supraspinal control of primary afferent depolarization (PAD) interneurons is disengaged, suggesting an increased role for sensory afferents. While increased H-reflex excitability in spastic individuals indicates a possible decrease in presynaptic inhibition, it remains unclear whether a decrease in sensory-evoked PAD contributes to this effect.• We investigated whether the PAD evoked by hindlimb afferents contributes to the change in presynaptic inhibition of the H-reflex in a decerebrated rat preparation. We found that chronic SCI decreases presynaptic inhibition of the plantar H-reflex through a reduction in PAD evoked by PBSt muscle group I afferents.• We further found that step-training restored presynaptic inhibition of the plantar H-reflex evoked by PBSt, suggesting the presence of activity-dependent plasticity of PAD pathways activated by flexor muscle group I afferents. ABSTRACT Spinal cord injury (SCI) results in the disruption of supraspinal control of spinal networks and an increase in the relative influence of afferent feedback to sublesional neural networks, both of which contribute to enhancing spinal reflex excitability. Hyperreflexia occurs in ~75% of individuals with chronic SCI and critically hinders functional recovery and quality of life. It is suggested to result from an increase in motoneuronal excitability and a decrease in presynaptic and postsynaptic inhibitory mechanisms. In contrast, locomotor training decreases hyperreflexia by restoring presynaptic inhibition.Primary afferent depolarization (PAD) is a powerful presynaptic inhibitory mechanism that selectively gates primary afferent transmission to spinal neurons to adjust reflex excitability and ensure smooth movement. However, the effect of chronic SCI and step-training on the reorganization of presynaptic inhibition evoked by hindlimb afferents, and the contribution of PAD has never been demonstrated. The objective of this study is to directly measure changes in presynaptic inhibition through dorsal root potentials (DRPs) and its association to plantar Hreflex inhibition. We provide direct evidence that H-reflex hyperexcitability is associated with a decrease in transmission of PAD pathways activated by PBSt afferents after chronic SCI. More precisely, we illustrate that PBSt group I muscle afferents evoke a similar pattern of inhibition onto both L4-DRPs and plantar H-reflexes evoked by the tibial nerve in Control and step-trained animals, but not in chronic SCI rats. These changes are not observed after step-training, suggesting a role for activity-dependent plasticity to regulate PAD pathways activated by flexor muscle group I afferents.

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“…The Cre expression pattern has been confirmed and found to faithfully recapitulate the endogenous Rorb expression pattern. [20][21][22] Currently, no suitable Rorb antibody for high-quality immunostaining is available, and thus the use of Rorb-IRES-Cre provides an alternative approach for tracing the Rorb expression pattern. When Rorb-IRES-Cre strain is crossed with the Cre reporter mouse strain Rosa26-CAG-Loxp-stop-Loxp-tdTomato (Ai9; abbreviated as Rosa26-CAG-LSL-tdTomato), 23 most, if not all, cells that express Rorb permanently express tdTomato in the Rorb-IRES-Cre/+; Rosa26-CAG-LSL-tdTomato/+ mice ( Figure 1B).…”

Section: Rorb-ires-cre Is a Highly Suitable Tool For Fate-mapping Amentioning

confidence: 99%

“…[20][21][22] Currently, no suitable Rorb antibody for high-quality immunostaining is available, and thus the use of Rorb-IRES-Cre provides an alternative approach for tracing the Rorb expression pattern. B, Rationale for how tdTomato expression faithfully recapitulates Rorb-IRES-Cre pattern.…”

mentioning

confidence: 99%

Fate‐mapping analysis using Rorb‐IRES‐Cre reveals apical‐to‐basal gradient of Rorb expression in mouse cochlea

Wang

et al. 2019

Developmental Dynamics

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Background: Conditional loss-of-function studies are widely conducted using the Cre/Loxp system because this helps circumvent embryonic or neonatal lethality problems. However, Cre strains specific to the inner ear are lacking, and thus lethality frequently occurs even in conditional knockout studies. Results: Here, we report a Rorb-IRES-Cre knockin mouse strain in which the Cre recapitulates the expression pattern of endogenous Rorb (RAR-related orphan receptor beta). Analysis of Rorb-IRES-Cre/+; Rosa26-CAG-LSL-tdTomato/+ cochlear samples revealed that tdTomato was expressed at the apical turn only by E12.5. TdTomato was observed in the apical and middle turns but was minimally expressed in the basal turn at E15.5, E18.5, and P5. However, most of the auditory hair cells (HCs) and supporting cells (SCs) in all three turns were tdTomato+ at P15 and P30. Intriguingly, no tdTomato+ vestibular cells were detected until P5 and a few cells were present at P15 and P30. Finally, we also confirmed Rorb mRNA and protein expression in cochlear HCs and SCs at P30. Conclusions: We reveal that Rorb expression exhibits an apical-to-basal gradient in cochleae. The cochlear-specific and apical-to-basal-gradient Rorb Cre activity should enable discrimination of gene functions in cochlear vs vestibular regions as well as low-frequency vs high-frequency regions in the cochlea. K E Y W O R D Scochlea, hair cell, inner ear, Rorb, supporting cell

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RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait

Cited by 92 publications

References 86 publications

Presynaptic Inhibition Selectively Gates Auditory Transmission to the Brainstem Startle Circuit

Presynaptic Inhibition Selectively Gates Auditory Transmission to the Brainstem Startle Circuit

Direct evidence for decreased presynaptic inhibition evoked by PBSt group I muscle afferents after chronic SCI and recovery with step-training in the decerebrated rat

Fate‐mapping analysis using Rorb‐IRES‐Cre reveals apical‐to‐basal gradient of Rorb expression in mouse cochlea

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