Targeted Ablation, Silencing, and Activation Establish Glycinergic Dorsal Horn Neurons as Key Components of a Spinal Gate for Pain and Itch

Foster, Edmund; Wildner, Hendrik; Tudeau, Laetitia; Haueter, Sabine; Ralvenius, William T.; Jegen, Monika; Johannssen, Helge C.; Hösli, Ladina; Haenraets, Karen; Ghanem, Alexander; Conzelmann, Karl‐Klaus; Bösl, Michael R.; Zeilhofer, Hanns Ulrich

doi:10.1016/j.neuron.2015.02.028

Cited by 316 publications

(351 citation statements)

References 69 publications

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“…Notably, overall motor function (as assayed by rotarod, grip strength and ladder rung behaviors) remains mostly intact in all of these manipulations of the dI4/dIL A lineage (Duan et al, 2014;Fink et al, 2014;Foster et al, 2015;Kardon et al, 2014). This suggests that dI4/dIL A lineage inhibitory neurons are not necessary for gross motor function and, therefore, that inhibitory neurons in the ventral spinal cord are primarily responsible for gross motor behavior (Arber, 2012;Goulding et al, 2014).…”

Section: Inhibitory Neuronsmentioning

confidence: 99%

“…These Ptf1a lineage neurons are a mixture of GABAergic and glycinergic neurons. Ablation of a subset of GABAergic neurons leads to defects in goal-directed reaching behavior and increased scratching behavior (Fink et al, 2014), while ablation or inhibition of glycinergic neurons (many of which also release GABA) leads to increased sensitivity to mechanical pain, thermal sensation and itch (Foster et al, 2015). While these studies have provided important insights, it should be noted that the manipulations could affect a large number of inhibitory neurons that comprise numerous subpopulations.…”

Section: Inhibitory Neuronsmentioning

confidence: 99%

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Making sense out of spinal cord somatosensory development

2016

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The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits.

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Section: Inhibitory Neuronsmentioning

confidence: 99%

Section: Inhibitory Neuronsmentioning

confidence: 99%

Making sense out of spinal cord somatosensory development

2016

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“…Foster et al (42) also found evidence consistent with the strong innervation of spinal glycinergic interneurons by nonnociceptive sensory neurons. In addition, ablation of glycinergic neurons resulted in hypersensitivity and spontaneous aversive behaviors, whereas their exogenous activation ameliorated neuropathic hyperalgesia (41).…”

Section: Specific Glycine Alterationsmentioning

confidence: 80%

Neuropathic Pain: A Review of Interneuronal Disinhibition

Alves

Lin

2018

Arch Neurosci

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Context: Dysfunction of pain circuitry may alter normal pain perception, leading to neuropathic pain. The underlying mechanisms are still unclear, although several animal models of partial nerve injury have been developed. Objectives: This review aimed to describe some essential elements for understanding neuropathic pain after peripheral nerve injury and to discuss its mechanisms with an emphasis on interneuronal disinhibition. Evidence Acquisition: A PubMed search was undertaken with no date restrictions, using a combination of the following keywords: "mechanisms", "allodynia", "peripheral nerve injury", "neuropathic pain", and "interneuronal disinhibition". Then, relevant papers on the underlying mechanisms of neuropathic pain after peripheral nerve injury were selected. Results: Several hypotheses have been proposed to explain neuropathic pain, which are not necessarily independent of each other. Interneuronal disinhibition is one of the most promising hypotheses, which includes several possible mechanisms, such as death of inhibitory interneurons (1), reduced afferent drive to inhibitory interneurons (2), depletion of gamma-aminobutyric acid (GABA) (3), GABA dysfunction (4), altered membrane properties of inhibitory interneurons (5), and specific glycine disruption (6). Currently, only some of these hypotheses are promising. Technical discrepancies among experimental studies are partially responsible for some of these controversial results. Conclusions: Formerly neglected circuitries including the glycinergic system, as well as other disturbances such as shift of GABA activity, currently constitute the most promising hypotheses on neuropathic pain. Additional studies on cell types involved in nociceptive transmission and dorsal horn connectivity of the spinal cord are still needed for a better understanding of pain circuitry and its disorders.

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“…Interneurons represent the majority of the neural population throughout the dorsal horn, and are particularly dense in laminae I, II and III (Todd and Koerber, 2013). Certain interneurons are inhibitory; they attenuate the transmission of nociceptive messages through the release of GABA or glycine (Foster et al, 2015;Todd and Koerber, 2013).…”

Section: Mechanisms For Modulating Painmentioning

confidence: 99%

Animal Consciousness

Neindre¹,

Bernard

Boissy

et al. 2017

EFSA Supporting Publications

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After reviewing the literature on current knowledge about consciousness in humans, we present a state-of-the art discussion on consciousness and related key concepts in animals. Obviously much fewer publications are available on non-human species than on humans, most of them relating to laboratory or wild animal species, and only few to livestock species. Human consciousness is by definition subjective and private. Animal consciousness is usually assessed through behavioural performance. Behaviour involves a wide array of cognitive processes that have to be assessed separately using specific experimental protocols. Accordingly, several processes indicative of the presence of consciousness are discussed: perception and cognition, awareness of the bodily-self, selfrelated knowledge of the environment (including social environment). When available, specific examples are given in livestock species. Next, we review the existing evidence regarding neuronal correlates of consciousness, and emphasize the difficulty of linking aspects of consciousness to specific neural structures across the phyla because high-level cognitive abilities may have evolved independently along evolution. Several mammalian brain structures (cortex and midbrain) are involved in the manifestations of consciousness, while the equivalent functional structures for birds and fishes would likely be the pallium/tectum and midbrain. Caution is required before excluding consciousness in species not having the same brain structures as the mammalian ones as different neural architectures may mediate comparable processes. Finally, specific neurophysiological mechanisms appear to be strongly linked to the emergence of consciousness, namely neural synchrony and neural feedback. Considering the limited amount of data available and the few animal species studied so far, we conclude that different manifestations of consciousness can be observed in animals but that further refinement is still needed to characterize their level and content in each species. Further research is required to clarify these issues, especially in livestock species.

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Targeted Ablation, Silencing, and Activation Establish Glycinergic Dorsal Horn Neurons as Key Components of a Spinal Gate for Pain and Itch

Cited by 316 publications

References 69 publications

Making sense out of spinal cord somatosensory development

Making sense out of spinal cord somatosensory development

Neuropathic Pain: A Review of Interneuronal Disinhibition

Animal Consciousness

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