Marc Landry - Academia.edu (original) (raw)
Papers by Marc Landry
Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive perip... more Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibres, is a useful model to study central sensitization to pain. Windup is expressed by neurons in of both dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adult remain controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adult, in vivo, depends on a synaptic balance between excitatory NMDA receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juveniles rats and that windup properties are the same regardless spinal network,...
Movement disorders : official journal of the Movement Disorder Society, Jan 18, 2018
Pain is a major non motor symptom that contributes to impaired quality of life in PD. However, it... more Pain is a major non motor symptom that contributes to impaired quality of life in PD. However, its mechanism is unknown. We sought to identify the pain phenotypes and parallel changes in spinal integration of peripheral stimuli in a rat model of PD induced by lesions of SN dopamine neurons, using behavioral plantar and von Frey tests as well as electrophysiology of the dorsal horn. We show that dopamine depletion by 6-OHDA induced hypersensitivity to mechanical and thermal stimuli. These abnormal behaviors were paralleled by increased neuronal responses and hyperexcitability of wide dynamic range neurons of lamina V of the dorsal horn of the spinal cord in response to electrical stimulation of the sciatic nerve in the 6-OHDA model as compared to sham rats. These results provide evidence for alteration of nociceptive integration in the spinal dorsal horn neurons in 6-OHDA rats that can reflect changes in pain behavior. © 2018 International Parkinson and Movement Disorder Society.
Frontiers in cellular neuroscience, 2014
MicroRNAs (miRNAs) are emerging as master regulators of gene expression in the nervous system whe... more MicroRNAs (miRNAs) are emerging as master regulators of gene expression in the nervous system where they contribute not only to brain development but also to neuronal network homeostasis and plasticity. Their function is the result of a cascade of events including miRNA biogenesis, target recognition, and translation inhibition. It has been suggested that miRNAs are major switches of the genome owing to their ability to regulate multiple genes at the same time. This regulation is essential for normal neuronal activity and, when affected, can lead to drastic pathological conditions. As an example, we illustrate how deregulation of miRNAs can affect neuronal plasticity leading to chronic pain. The origin of pain and its dual role as a key physiological function and a debilitating disease has been highly debated until now. The incidence of chronic pain is estimated to be 20-25% worldwide, thus making it a public health problem. Chronic pain can be considered as a form of maladaptive pl...
Nature Neuroscience, 2014
Trends in Pharmacological Sciences, 2007
The Journal of Physiology, 2011
Non‐technical summary The dorsal horn of the spinal cord is the first site in the central nervou... more Non‐technical summary The dorsal horn of the spinal cord is the first site in the central nervous system where painful sensory information is processed before transmission to the brain. In vitro recordings in spinal slices established that this processing relies on both plasticity of synaptic connections and intrinsic electrical properties of dorsal horn neurones (DHNs). DHNs may generate plateau potentials, which underlie intense discharges and long‐lasting after‐discharges in response to a brief stimulation, and represent a putative endogenous mechanism for amplification of painful sensory inputs. Using patch‐clamp recordings in the anaesthetized adult rat, we show that DHNs do generate plateau potentials in vivo, which shape their responses to natural sensory stimulation. Moreover, we give direct evidence for the involvement of these amplification properties in both short‐term (windup) and long‐term sensitisation associated with neuropathic pain, raising the possibility that pla...
The EMBO Journal, 2011
Chronic pain states are characterized by long-term sensitization of spinal cord neurons that rela... more Chronic pain states are characterized by long-term sensitization of spinal cord neurons that relay nociceptive information to the brain. Among the mechanisms involved, up-regulation of Cav1.2-comprising L-type calcium channel (Cav1.2-LTC) in spinal dorsal horn have a crucial role in chronic neuropathic pain. Here, we address a mechanism of translational regulation of this calcium channel. Translational regulation by microRNAs is a key factor in the expression and function of eukaryotic genomes. Because perfect matching to target sequence is not required for inhibition, theoretically, microRNAs could regulate simultaneously multiple mRNAs. We show here that a single microRNA, miR-103, simultaneously regulates the expression of the three subunits forming Cav1.2-LTC in a novel integrative regulation. This regulation is bidirectional since knocking-down or over-expressing miR-103, respectively, up-or down-regulate the level of Cav1.2-LTC translation. Functionally, we show that miR-103 knockdown in naive rats results in hypersensitivity to pain. Moreover, we demonstrate that miR-103 is downregulated in neuropathic animals and that miR-103 intrathecal applications successfully relieve pain, identifying miR-103 as a novel possible therapeutic target in neuropathic chronic pain.
Review of Scientific Instruments, 2006
In this article we present a complete laser scanning microscope designed for simultaneous spectra... more In this article we present a complete laser scanning microscope designed for simultaneous spectral and lifetime measurements from every point of the specimen located within the field of view. The pulsed laser source used for two-photon excitation provides good spatial resolution with minimal invasivity. In addition, the detection module was optimized for minimal photon loss, allowing laser power minimization and further reduction of cells photodamage. Analysis of biological samples illustrates the performances of this configuration, particularly when applied to fluorescent resonance energy transfer (FRET) measurements. Indeed, multiparametric acquisition is particularly useful to discriminate between FRET and artifactual response due to acquisition invasivity or cell heterogeneity. Combined with adapted homemade driving software, this system is stable, portable, and optimized for living cell studies.
Regulatory Peptides, 2004
Tumor galanin content was measured in extracts from human pituitary adenomas using a specific RIA... more Tumor galanin content was measured in extracts from human pituitary adenomas using a specific RIA method for monitoring human galanin. Twenty-two out of twenty-four tumors contained galanin with notably high levels in corticotroph adenomas, varying levels in clinically inactive tumors, and low levels in GH secreting adenomas. Tumor galanin and ACTH contents were closely correlated in all tumors. In four young patients with microadenomas and highly active Mb Cushing tumor galanin was inversely related to tumor volume. The molecular form of tumor galanin, studied with reverse-phase HPLC, was homogenous with the majority of tumor galanin coeluting with standard human galanin. In the tumors analysed with in situ hybridization there was a good correlation between galanin peptide levels and galanin mRNA expression. In some tumors galanin mRNA and POMC levels coexisted, in others they were essentially in different cell populations. Levels of plasma galanin-LI were not related to tumor galanin concentration, and galanin levels were in the same range in sinus petrosus close to the pituitary venous drainage as in peripheral blood. Corticotrophin releasing hormone injections in two patients caused ACTH, but no detectable galanin release into sinus petrosus. Our results demonstrate that corticotroph, but not GH adenomas, express high levels of galanin, in addition to ACTH, and that in some tumors both polypeptides are synthesised in the same cell population. However, galanin levels in plasma were not influenced by the tumor galanin content.
Peptides, 2000
In the rat hypothalamic magnocellular neurons, galanin coexists with vasopressin and might be inv... more In the rat hypothalamic magnocellular neurons, galanin coexists with vasopressin and might be involved in hydro-osmotic regulation. In the present study, we investigated the ability of galanin to also regulate the osmotically stimulated expression of galanin itself in hypothalamic magnocellular neurons. Ten minutes after galanin injection, galanin mRNA rate decreased in salt-loaded rats whereas the level of galanin immunoreactivity increased. Both effects were suppressed by the injection of a galanin antagonist together with galanin. Moreover, electron microscope studies demonstrated synaptic contacts between galanin-containing fibers and magnocellular neurons. Galanin may exert inhibitory roles in the regulation of magnocellular neurons. However, galanin and vasopressin expression displayed differences upon galanin injection. Possible mechanisms underlying these discrepancies are further discussed.
Pain, 2013
In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the exci... more In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the spinal dorsal horn. We investigated the deregulation of the synaptogenic neuroligin (NL) molecules, whose NL1 and NL2 isoforms are primarily encountered at excitatory and inhibitory synapses, respectively. In the dorsal horn of SNL rats, NL2 was overexpressed whereas NL1 remained unchanged. In control animals, intrathecal injections of small interfering RNA (siRNA) targeting NL2 increased mechanical sensitivity, which confirmed the association of NL2 with inhibition. By contrast, siRNA application produced antinociceptive effects in SNL rats. Regarding NL partners, expression of the excitatory postsynaptic scaffolding protein PSD95 unexpectedly covaried with NL2 overexpression, and NL2/PSD95 protein interaction and colocalization increased. Expression of the inhibitory scaffolding protein gephyrin remained unchanged, indicating a partial change in NL2 postsynaptic partners in SNL rats. This phenomenon appears to be specific to the NL2(-) isoform. Our data showed unexpected upregulation and pronociceptive effects of the "inhibitory" NL2 in neuropathic pain, suggesting a functional shift of NL2 from inhibition to excitation that changed the synaptic ratio toward higher excitation.
Nature Neuroscience, 2003
Journal of Neurochemistry, 2007
Functional cross‐talk between structurally unrelated P2X ATP receptors and members of the ‘cys‐lo... more Functional cross‐talk between structurally unrelated P2X ATP receptors and members of the ‘cys‐loop’ receptor‐channel superfamily represents a recently‐discovered mechanism for rapid modulation of information processing. The extent and the mechanism of the inhibitory cross‐talks between these two classes of ionotropic receptors remain poorly understood, however. Both ionic and molecular coupling were proposed to explain cross‐inhibition between P2X subtypes and GABAA receptors, suggesting a P2X subunit‐dependent mechanism. We show here that cross‐inhibition between neuronal P2X3 or P2X2+3 and GABAA receptors does not depend on chloride and calcium ions. We identified an intracellular QST386–388 motif in P2X3 subunits which is required for the functional coupling with GABAA receptors. Moreover the cross‐inhibition between native P2X3 and GABA receptors in cultured rat dorsal root ganglia (DRG) neurons is abolished by infusion of a peptide containing the QST motif as well as by viral ...
The Journal of Comparative Neurology, 2006
The 29/30 amino acid neuropeptide galanin has been implicated in pain processing at the spinal le... more The 29/30 amino acid neuropeptide galanin has been implicated in pain processing at the spinal level and local dorsal horn neurons expressing the Gal(1) receptor may play a critical role. In order to determine the transmitter identity of these neurons, we used immunohistochemistry and antibodies against the Gal(1) receptor and the three vesicular glutamate transporters (VGLUTs), as well as in situ hybridization, to explore a possible glutamatergic phenotype. Gal(1) protein, which could not be demonstrated in Gal(1) knockout mice, colocalized with VGLUT2 protein, but not with glutamate decarboxylase, in many nerve endings in lamina II. Moreover, Gal(1) and VGLUT2 transcripts were often found in the same cell bodies in laminae I-IV. Gal(1)-protein and galanin-peptide showed an overlapping distribution but were not colocalized. Gal(1) staining did not appear to be affected by dorsal rhizotomy. Taken together, these findings provide strong evidence that Gal(1) is a heteroreceptor expressed on excitatory glutamatergic dorsal horn interneurons. Activation of such Gal(1) receptors may thus decrease the inhibitory tone in the superficial dorsal horn, and possibly cause antinociception.
Journal de la Société de Biologie, 2009
Experimental Neurology, 2000
European Journal of Neuroscience, 2004
Electromyographic (EMG) analysis was used to provide an assessment of the recovery of locomotion ... more Electromyographic (EMG) analysis was used to provide an assessment of the recovery of locomotion in spinal-transected adult salamanders (Pleurodeles waltlii). EMG recordings were performed during swimming and overground stepping in the same animal before and at various times (up to 500 days) after a mid-trunk spinalization. Two-three weeks after spinalization, locomotor EMG activity was limited to the forelimbs and the body rostral to the transection. Thereafter, there was a return of the locomotor EMG activity at progressively more caudal levels below the transection. The animals reached stable locomotor patterns 3-4 months post-transection. Several locomotor parameters (cycle duration, burst duration, burst proportion, intersegmental phase lag, interlimb coupling) measured at various recovery times after spinalization were compared with those in intact animals. These comparisons revealed transient and long-term alterations in the locomotor parameters both above and below the transection site. These alterations were much more pronounced for swimming than for stepping and revealed differences in adaptive plasticity between the two locomotor networks. Recovered locomotor activity was immediately abolished by retransection at the site of the original spinalization, suggesting that the spinal cord caudal to the transection was reinnervated by descending brain and/or propriospinal axons, and that this regeneration contributed to the restoration of locomotor activity. Anatomical studies conducted in parallel further demonstrated that some of the regenerated axons came from glutamatergic and serotoninergic immunoreactive cells within the reticular formation.
European Journal of Neuroscience, 2003
Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive perip... more Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibres, is a useful model to study central sensitization to pain. Windup is expressed by neurons in of both dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adult remain controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adult, in vivo, depends on a synaptic balance between excitatory NMDA receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juveniles rats and that windup properties are the same regardless spinal network,...
Movement disorders : official journal of the Movement Disorder Society, Jan 18, 2018
Pain is a major non motor symptom that contributes to impaired quality of life in PD. However, it... more Pain is a major non motor symptom that contributes to impaired quality of life in PD. However, its mechanism is unknown. We sought to identify the pain phenotypes and parallel changes in spinal integration of peripheral stimuli in a rat model of PD induced by lesions of SN dopamine neurons, using behavioral plantar and von Frey tests as well as electrophysiology of the dorsal horn. We show that dopamine depletion by 6-OHDA induced hypersensitivity to mechanical and thermal stimuli. These abnormal behaviors were paralleled by increased neuronal responses and hyperexcitability of wide dynamic range neurons of lamina V of the dorsal horn of the spinal cord in response to electrical stimulation of the sciatic nerve in the 6-OHDA model as compared to sham rats. These results provide evidence for alteration of nociceptive integration in the spinal dorsal horn neurons in 6-OHDA rats that can reflect changes in pain behavior. © 2018 International Parkinson and Movement Disorder Society.
Frontiers in cellular neuroscience, 2014
MicroRNAs (miRNAs) are emerging as master regulators of gene expression in the nervous system whe... more MicroRNAs (miRNAs) are emerging as master regulators of gene expression in the nervous system where they contribute not only to brain development but also to neuronal network homeostasis and plasticity. Their function is the result of a cascade of events including miRNA biogenesis, target recognition, and translation inhibition. It has been suggested that miRNAs are major switches of the genome owing to their ability to regulate multiple genes at the same time. This regulation is essential for normal neuronal activity and, when affected, can lead to drastic pathological conditions. As an example, we illustrate how deregulation of miRNAs can affect neuronal plasticity leading to chronic pain. The origin of pain and its dual role as a key physiological function and a debilitating disease has been highly debated until now. The incidence of chronic pain is estimated to be 20-25% worldwide, thus making it a public health problem. Chronic pain can be considered as a form of maladaptive pl...
Nature Neuroscience, 2014
Trends in Pharmacological Sciences, 2007
The Journal of Physiology, 2011
Non‐technical summary The dorsal horn of the spinal cord is the first site in the central nervou... more Non‐technical summary The dorsal horn of the spinal cord is the first site in the central nervous system where painful sensory information is processed before transmission to the brain. In vitro recordings in spinal slices established that this processing relies on both plasticity of synaptic connections and intrinsic electrical properties of dorsal horn neurones (DHNs). DHNs may generate plateau potentials, which underlie intense discharges and long‐lasting after‐discharges in response to a brief stimulation, and represent a putative endogenous mechanism for amplification of painful sensory inputs. Using patch‐clamp recordings in the anaesthetized adult rat, we show that DHNs do generate plateau potentials in vivo, which shape their responses to natural sensory stimulation. Moreover, we give direct evidence for the involvement of these amplification properties in both short‐term (windup) and long‐term sensitisation associated with neuropathic pain, raising the possibility that pla...
The EMBO Journal, 2011
Chronic pain states are characterized by long-term sensitization of spinal cord neurons that rela... more Chronic pain states are characterized by long-term sensitization of spinal cord neurons that relay nociceptive information to the brain. Among the mechanisms involved, up-regulation of Cav1.2-comprising L-type calcium channel (Cav1.2-LTC) in spinal dorsal horn have a crucial role in chronic neuropathic pain. Here, we address a mechanism of translational regulation of this calcium channel. Translational regulation by microRNAs is a key factor in the expression and function of eukaryotic genomes. Because perfect matching to target sequence is not required for inhibition, theoretically, microRNAs could regulate simultaneously multiple mRNAs. We show here that a single microRNA, miR-103, simultaneously regulates the expression of the three subunits forming Cav1.2-LTC in a novel integrative regulation. This regulation is bidirectional since knocking-down or over-expressing miR-103, respectively, up-or down-regulate the level of Cav1.2-LTC translation. Functionally, we show that miR-103 knockdown in naive rats results in hypersensitivity to pain. Moreover, we demonstrate that miR-103 is downregulated in neuropathic animals and that miR-103 intrathecal applications successfully relieve pain, identifying miR-103 as a novel possible therapeutic target in neuropathic chronic pain.
Review of Scientific Instruments, 2006
In this article we present a complete laser scanning microscope designed for simultaneous spectra... more In this article we present a complete laser scanning microscope designed for simultaneous spectral and lifetime measurements from every point of the specimen located within the field of view. The pulsed laser source used for two-photon excitation provides good spatial resolution with minimal invasivity. In addition, the detection module was optimized for minimal photon loss, allowing laser power minimization and further reduction of cells photodamage. Analysis of biological samples illustrates the performances of this configuration, particularly when applied to fluorescent resonance energy transfer (FRET) measurements. Indeed, multiparametric acquisition is particularly useful to discriminate between FRET and artifactual response due to acquisition invasivity or cell heterogeneity. Combined with adapted homemade driving software, this system is stable, portable, and optimized for living cell studies.
Regulatory Peptides, 2004
Tumor galanin content was measured in extracts from human pituitary adenomas using a specific RIA... more Tumor galanin content was measured in extracts from human pituitary adenomas using a specific RIA method for monitoring human galanin. Twenty-two out of twenty-four tumors contained galanin with notably high levels in corticotroph adenomas, varying levels in clinically inactive tumors, and low levels in GH secreting adenomas. Tumor galanin and ACTH contents were closely correlated in all tumors. In four young patients with microadenomas and highly active Mb Cushing tumor galanin was inversely related to tumor volume. The molecular form of tumor galanin, studied with reverse-phase HPLC, was homogenous with the majority of tumor galanin coeluting with standard human galanin. In the tumors analysed with in situ hybridization there was a good correlation between galanin peptide levels and galanin mRNA expression. In some tumors galanin mRNA and POMC levels coexisted, in others they were essentially in different cell populations. Levels of plasma galanin-LI were not related to tumor galanin concentration, and galanin levels were in the same range in sinus petrosus close to the pituitary venous drainage as in peripheral blood. Corticotrophin releasing hormone injections in two patients caused ACTH, but no detectable galanin release into sinus petrosus. Our results demonstrate that corticotroph, but not GH adenomas, express high levels of galanin, in addition to ACTH, and that in some tumors both polypeptides are synthesised in the same cell population. However, galanin levels in plasma were not influenced by the tumor galanin content.
Peptides, 2000
In the rat hypothalamic magnocellular neurons, galanin coexists with vasopressin and might be inv... more In the rat hypothalamic magnocellular neurons, galanin coexists with vasopressin and might be involved in hydro-osmotic regulation. In the present study, we investigated the ability of galanin to also regulate the osmotically stimulated expression of galanin itself in hypothalamic magnocellular neurons. Ten minutes after galanin injection, galanin mRNA rate decreased in salt-loaded rats whereas the level of galanin immunoreactivity increased. Both effects were suppressed by the injection of a galanin antagonist together with galanin. Moreover, electron microscope studies demonstrated synaptic contacts between galanin-containing fibers and magnocellular neurons. Galanin may exert inhibitory roles in the regulation of magnocellular neurons. However, galanin and vasopressin expression displayed differences upon galanin injection. Possible mechanisms underlying these discrepancies are further discussed.
Pain, 2013
In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the exci... more In the spinal nerve ligation (SNL) model of neuropathic pain, synaptic plasticity shifts the excitation/inhibition balance toward excitation in the spinal dorsal horn. We investigated the deregulation of the synaptogenic neuroligin (NL) molecules, whose NL1 and NL2 isoforms are primarily encountered at excitatory and inhibitory synapses, respectively. In the dorsal horn of SNL rats, NL2 was overexpressed whereas NL1 remained unchanged. In control animals, intrathecal injections of small interfering RNA (siRNA) targeting NL2 increased mechanical sensitivity, which confirmed the association of NL2 with inhibition. By contrast, siRNA application produced antinociceptive effects in SNL rats. Regarding NL partners, expression of the excitatory postsynaptic scaffolding protein PSD95 unexpectedly covaried with NL2 overexpression, and NL2/PSD95 protein interaction and colocalization increased. Expression of the inhibitory scaffolding protein gephyrin remained unchanged, indicating a partial change in NL2 postsynaptic partners in SNL rats. This phenomenon appears to be specific to the NL2(-) isoform. Our data showed unexpected upregulation and pronociceptive effects of the "inhibitory" NL2 in neuropathic pain, suggesting a functional shift of NL2 from inhibition to excitation that changed the synaptic ratio toward higher excitation.
Nature Neuroscience, 2003
Journal of Neurochemistry, 2007
Functional cross‐talk between structurally unrelated P2X ATP receptors and members of the ‘cys‐lo... more Functional cross‐talk between structurally unrelated P2X ATP receptors and members of the ‘cys‐loop’ receptor‐channel superfamily represents a recently‐discovered mechanism for rapid modulation of information processing. The extent and the mechanism of the inhibitory cross‐talks between these two classes of ionotropic receptors remain poorly understood, however. Both ionic and molecular coupling were proposed to explain cross‐inhibition between P2X subtypes and GABAA receptors, suggesting a P2X subunit‐dependent mechanism. We show here that cross‐inhibition between neuronal P2X3 or P2X2+3 and GABAA receptors does not depend on chloride and calcium ions. We identified an intracellular QST386–388 motif in P2X3 subunits which is required for the functional coupling with GABAA receptors. Moreover the cross‐inhibition between native P2X3 and GABA receptors in cultured rat dorsal root ganglia (DRG) neurons is abolished by infusion of a peptide containing the QST motif as well as by viral ...
The Journal of Comparative Neurology, 2006
The 29/30 amino acid neuropeptide galanin has been implicated in pain processing at the spinal le... more The 29/30 amino acid neuropeptide galanin has been implicated in pain processing at the spinal level and local dorsal horn neurons expressing the Gal(1) receptor may play a critical role. In order to determine the transmitter identity of these neurons, we used immunohistochemistry and antibodies against the Gal(1) receptor and the three vesicular glutamate transporters (VGLUTs), as well as in situ hybridization, to explore a possible glutamatergic phenotype. Gal(1) protein, which could not be demonstrated in Gal(1) knockout mice, colocalized with VGLUT2 protein, but not with glutamate decarboxylase, in many nerve endings in lamina II. Moreover, Gal(1) and VGLUT2 transcripts were often found in the same cell bodies in laminae I-IV. Gal(1)-protein and galanin-peptide showed an overlapping distribution but were not colocalized. Gal(1) staining did not appear to be affected by dorsal rhizotomy. Taken together, these findings provide strong evidence that Gal(1) is a heteroreceptor expressed on excitatory glutamatergic dorsal horn interneurons. Activation of such Gal(1) receptors may thus decrease the inhibitory tone in the superficial dorsal horn, and possibly cause antinociception.
Journal de la Société de Biologie, 2009
Experimental Neurology, 2000
European Journal of Neuroscience, 2004
Electromyographic (EMG) analysis was used to provide an assessment of the recovery of locomotion ... more Electromyographic (EMG) analysis was used to provide an assessment of the recovery of locomotion in spinal-transected adult salamanders (Pleurodeles waltlii). EMG recordings were performed during swimming and overground stepping in the same animal before and at various times (up to 500 days) after a mid-trunk spinalization. Two-three weeks after spinalization, locomotor EMG activity was limited to the forelimbs and the body rostral to the transection. Thereafter, there was a return of the locomotor EMG activity at progressively more caudal levels below the transection. The animals reached stable locomotor patterns 3-4 months post-transection. Several locomotor parameters (cycle duration, burst duration, burst proportion, intersegmental phase lag, interlimb coupling) measured at various recovery times after spinalization were compared with those in intact animals. These comparisons revealed transient and long-term alterations in the locomotor parameters both above and below the transection site. These alterations were much more pronounced for swimming than for stepping and revealed differences in adaptive plasticity between the two locomotor networks. Recovered locomotor activity was immediately abolished by retransection at the site of the original spinalization, suggesting that the spinal cord caudal to the transection was reinnervated by descending brain and/or propriospinal axons, and that this regeneration contributed to the restoration of locomotor activity. Anatomical studies conducted in parallel further demonstrated that some of the regenerated axons came from glutamatergic and serotoninergic immunoreactive cells within the reticular formation.
European Journal of Neuroscience, 2003