The Experts below are selected from a list of 111 Experts worldwide ranked by ideXlab platform
V. Reggie Edgerton - One of the best experts on this subject based on the ideXlab platform.
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Dose dependence of the 5-HT agonist Quipazine in facilitating spinal stepping in the rat with epidural stimulation.
Neuroscience letters, 2008Co-Authors: Ronaldo M. Ichiyama, Roland R. Roy, Yury Gerasimenko, Hui Zhong, Devin L. Jindrich, V. Reggie EdgertonAbstract:Epidural electrical stimulation (ES) at spinal cord segment L2 can produce coordinated step-like movements in completely spinalized adult rats [R.M. Ichiyama, Y.P. Gerasimenko, H. Zhong, R.R. Roy, V.R. Edgerton, Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation, Neurosci. Lett. 383 (2005) 339–344]. Plantar placement of the paws, however, was rarely observed. Here, we sought to determine the dose dependence of a 5-HT agonist (Quipazine) on stepping kinematics when administered in combination with ES. Six adult female Sprague–Dawley rats received a complete mid-thoracic spinal cord transection and were implanted with epidural electrodes at the L2 spinal cord level. Quipazine (i.p.) was tested at doses of 0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg. Rats were placed in a body weight support system, allowing them to walk bipedally on a moving treadmill belt (7 cm/s). 3D step kinematics analysis revealed that coordinated alternating bilateral stepping was induced by L2 stimulation (50 Hz) alone and by Quipazine alone. Furthermore, the combination treatment produced significantly greater numbers of plantar steps and improved quality of stepping compared to either intervention alone. Both number and quality of stepping peaked at the intermediate dose of 0.3–0.4 mg/kg. The results indicate that Quipazine and ES can have complementary effects on spinal circuits and that Quipazine dosage is an important factor in differentially modulating these circuitries to improve the quality of the bipedal stepping on a treadmill belt.
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Epidural spinal cord stimulation plus Quipazine administration enable stepping in complete spinal adult rats
Journal of neurophysiology, 2007Co-Authors: Yury Gerasimenko, Roland R. Roy, Ronaldo M. Ichiyama, Igor Lavrov, Grégoire Courtine, Lance Cai, Hui Zhong, V. Reggie EdgertonAbstract:We hypothesized that epidural spinal cord stimulation (ES) and Quipazine (a serotonergic agonist) modulates the excitability of flexor and extensor related intraspinal neural networks in qualitatively unique, but complementary, ways to facilitate locomotion in spinal cord-injured rats. To test this hypothesis, we stimulated (40 Hz) the S(1) spinal segment before and after Quipazine administration (0.3 mg/kg, ip) in bipedally step-trained and nontrained, adult, complete spinal (mid-thoracic) rats. The stepping pattern of these rats was compared with control rats. At the stimulation levels used, stepping was elicited only when the hindlimbs were placed on a moving treadmill. In nontrained rats, the stepping induced by ES and Quipazine administration was non-weight bearing, and the cycle period was shorter than in controls. In contrast, the stepping induced by ES and Quipazine in step-trained rats was highly coordinated with clear plantar foot placement and partial weight bearing. The effect of ES and Quipazine on EMG burst amplitude and duration was greater in flexor than extensor motor pools. Using fast Fourier transformation analysis of EMG bursts during ES, we observed one dominant peak at 40 Hz in the medial gastrocnemius (ankle extensor), whereas there was less of dominant spectral peak in the tibialis anterior (ankle flexor). We suggest that these frequency distributions reflect amplitude modulation of predominantly monosynaptic potentials in the extensor and predominantly polysynaptic pathways in the flexor muscle. Quipazine potentiated the amplitude of these responses. The data suggest that there are fundamental differences in the circuitry that generates flexion and extension during locomotion.
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Spinal cord-transected mice learn to step in response to Quipazine treatment and robotic training.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005Co-Authors: Andy J. Fong, L.l. Cai, Chad K. Otoshi, David J. Reinkensmeyer, Joel W. Burdick, Roland R. Roy, V. Reggie EdgertonAbstract:In the present study, concurrent treatment with robotic step training and a serotonin agonist, Quipazine, generated significant recovery of locomotor function in complete spinal cord-transected mice (T7–T9) that otherwise could not step. The extent of recovery achieved when these treatments were combined exceeded that obtained when either treatment was applied independently. We quantitatively analyzed the stepping characteristics of spinal mice after alternatively administering no training, manual training, robotic training, Quipazine treatment, or a combination of robotic training with Quipazine treatment, to examine the mechanisms by which training and Quipazine treatment promote functional recovery. Using fast Fourier transform and principal components analysis, significant improvements in the step rhythm, step shape consistency, and number of weight-bearing steps were observed in robotically trained compared with manually trained or nontrained mice. In contrast, manual training had no effect on stepping performance, yielding no improvement compared with nontrained mice. Daily bolus Quipazine treatment acutely improved the step shape consistency and number of steps executed by both robotically trained and nontrained mice, but these improvements did not persist after Quipazine was withdrawn. At the dosage used (0.5 mg/kg body weight), Quipazine appeared to facilitate, rather than directly generate, stepping, by enabling the spinal cord neural circuitry to process specific patterns of sensory information associated with weight-bearing stepping. Via this mechanism, Quipazine treatment enhanced kinematically appropriate robotic training. When administered intermittently during an extended period of robotic training, Quipazine revealed training-induced stepping improvements that were masked in the absence of the pharmacological treatment.
Franziska Wollnik - One of the best experts on this subject based on the ideXlab platform.
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5-HT3 receptor-mediated photic-like responses of the circadian clock in the rat.
Neuropharmacology, 2007Co-Authors: Caroline Graff, Paul Pevet, Etienne Challet, Franziska WollnikAbstract:Serotonin (5-HT) and 5-HT agonists have various resetting effects on the master clock, located in the suprachiasmatic nucleus (SCN), depending on the species. In rats, they induce photic-like effects on both locomotor activity rhythms and gene expression in the SCN. The 5 HT receptor(s) mediating these effects at circadian time 22 are localized in the SCN, most likely at a presynaptic level, on the retinohypothalamic terminals (RHT) known to convey photic information by releasing glutamate. Indeed, RHT degeneration blocks photic-like effects of a non-specific 5 HT agonist, Quipazine. However, the 5-HT receptor subtype(s) involved is still unknown, although 5-HT3 receptor activation is known to induce glutamate release. We thus analyzed the effects of selective 5 HT3 agonist and antagonist, as well as a specific NMDA receptor antagonist, on different parameters of the clock. This study shows that the 5-HT3 receptor mediates the resetting effects of Quipazine on locomotor activity rhythms. The 5-HT3 receptor is only partially implicated in Quipazine-induced expression of c-FOS, while NMDA receptor inhibition blocks Quipazine photic-like effects on both parameters. Taken together, photic-like responses produced by 5-HT stimulation in rats are likely mediated by (presynaptic ?) 5-HT3 receptor activation followed by NMDA receptor activation.
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Involvement of the retinohypothalamic tract in the photic-like effects of the serotonin agonist Quipazine in the rat.
Neuroscience, 2005Co-Authors: Carole Graff, Markus Kohler, Paul Pevet, Franziska WollnikAbstract:Light is the major synchronizer of the mammalian circadian pacemaker located in the suprachiasmatic nucleus. Photic information is perceived by the retina and conveyed to the suprachiasmatic nucleus either directly by the retinohypothalamic tract or indirectly by the intergeniculate leaflet and the geniculohypothalamic tract. In addition, serotonin has been shown to affect the suprachiasmatic nucleus by both direct and indirect serotonin projections from the raphe nuclei. Indeed, systemic as well as local administrations of the serotonin agonist Quipazine in the region of the suprachiasmatic nucleus mimic the effects of light on the circadian system of rats, i.e. they induce phase-advances of the locomotor activity rhythm as well as c-FOS expression in the suprachiasmatic nucleus during late subjective night. The aim of this study was to localize the site(s) of action mediating those effects. Phase shifts of the locomotor activity rhythm as well as c-FOS expression in the suprachiasmatic nucleus after s.c. injection of Quipazine (10 mg/kg) were assessed in Lewis rats, which had received either radio-frequency lesions of the intergeniculate leaflet or infusions of the serotonin neurotoxin 5,7-dihydroxytryptamine into the suprachiasmatic nucleus (25 microg) or bilateral enucleation. Lesions of intergeniculate leaflet and serotonin afferents to the suprachiasmatic nucleus did not reduce the photic-like effects of Quipazine, whereas bilateral enucleation and the subsequent degeneration of the retinohypothalamic tract abolished both the phase-shifting and the FOS-inducing effects of Quipazine. The results indicate that photic-like effects of Quipazine are mediated via the retinohypothalamic tract.
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Serotonin agonist Quipazine induces photic-like phase shifts of the circadian activity rhythm and c-Fos expression in the rat suprachiasmatic nucleus.
Journal of biological rhythms, 1999Co-Authors: Markus Kohler, Andreas Kalkowski, Franziska WollnikAbstract:Nonphotic stimuli can reset and entrain circadian activity rhythms in hamsters and mice, and serotonin is thought to be involved in the phase-resetting effects of these stimuli. In the present study, the authors examined the effect of the serotonin agonist Quipazine on circadian activity rhythms in three inbred strains of rats (ACI, BH, and LEW). Furthermore, they investigated the effect of Quipazine on the expression of c-Fos in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Quipazine reduced the amount of running wheel activity for 3 h after treatment, however, no long-term changes in τ and in the activity level were observed. More important, Quipazine induced significant phase advances of the activity rhythm and c-Fos production in the SCN at the end of the subjective night (Circadian Time [CT] 22), whereas neither phase shifts nor c-Fos induction were observed during the subjective day. Quipazine injections also resulted in moderate phase delays at the beginning of the subjectiv...
Phillip F Gardiner - One of the best experts on this subject based on the ideXlab platform.
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daily passive cycling attenuates the hyperexcitability and restores the responsiveness of the extensor monosynaptic reflex to Quipazine in the chronic spinally transected rat
Journal of Neurotrauma, 2014Co-Authors: Jeremy W Chopek, Christopher W Macdonell, Kalan Gardiner, Phillip F GardinerAbstract:Activity-based interventions such as locomotor training or passive cycling have a positive influence on the spinal circuitry and recovery following a spinal cord injury (SCI). The use of Quipazine in combination with exercise training has demonstrated a greater functional recovery than has exercise training alone. However, the influence of exercise or training on the responsiveness of the spinal cord to Quipazine has not been examined following a chronic spinal transection. The purpose of this study was to characterize the flexor and extensor monosynaptic reflex (MSR) response pre- and post-Quipazine in chronic complete spinally transected rats that either underwent daily passive cycling for 3 months or did not receive passive cycling. Following a chronic spinal transection, the extensor MSR demonstrated a hyperreflexive response (fivefold increase) to afferent stimuli, and did not respond to Quipazine injection. With daily passive cycling, the extensor MSR hyperexcitability was attenuated, and the MSR amplitude increased 72% following Quipazine injection (p<0.004), which was comparable to the extensor MSR response (94%) in the control group. For both chronic spinal transection groups, the flexor MSR amplitudes were not altered following Quipazine injection, whereas in the control group the flexor MSR amplitude increased 86% in response to Quipazine (p<0.004). These results demonstrate that passive cycling attenuates the hyperreflexive response of the extensor MSR following a chronic SCI, and restores the MSR response to Quipazine.
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Daily Passive Cycling Attenuates the Hyperexcitability and Restores the Responsiveness of the Extensor Monosynaptic Reflex to Quipazine in the Chronic Spinally Transected Rat
Journal of neurotrauma, 2014Co-Authors: Jeremy W Chopek, Christopher W Macdonell, Kalan Gardiner, Phillip F GardinerAbstract:Activity-based interventions such as locomotor training or passive cycling have a positive influence on the spinal circuitry and recovery following a spinal cord injury (SCI). The use of Quipazine in combination with exercise training has demonstrated a greater functional recovery than has exercise training alone. However, the influence of exercise or training on the responsiveness of the spinal cord to Quipazine has not been examined following a chronic spinal transection. The purpose of this study was to characterize the flexor and extensor monosynaptic reflex (MSR) response pre- and post-Quipazine in chronic complete spinally transected rats that either underwent daily passive cycling for 3 months or did not receive passive cycling. Following a chronic spinal transection, the extensor MSR demonstrated a hyperreflexive response (fivefold increase) to afferent stimuli, and did not respond to Quipazine injection. With daily passive cycling, the extensor MSR hyperexcitability was attenuated, and the MSR amplitude increased 72% following Quipazine injection (p
Donald J. Stehouwer - One of the best experts on this subject based on the ideXlab platform.
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L-DOPA and Quipazine elicit air-stepping in neonatal rats with spinal cord transections.
Behavioral neuroscience, 1997Co-Authors: Melanie L. Mcewen, C. Van Hartesveldt, Donald J. StehouwerAbstract:Acute mid-thoracic spinal cord transection eliminates hindlimb air-stepping in neonatal rats suspended in harnesses and administered L-DOPA. Because spinal cord transection eliminates all descending inputs to the hindlimb locomotor circuits, this experiment determined if coadministration of L-DOPA and Quipazine (serotonin receptor agonist) would induce hindlimb air-stepping in rat pups 24 hr after transection. Hindlimb steps of spinally transected pups that received L-DOPA or Quipazine alone were infrequent and slow; hindlimb steps induced by L-DOPA + Quipazine occurred more frequently and were faster than those elicited by either drug alone. These findings suggest that catecholaminergic and serotonergic systems both contribute to hindlimb stepping.
Roland R. Roy - One of the best experts on this subject based on the ideXlab platform.
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Dose dependence of the 5-HT agonist Quipazine in facilitating spinal stepping in the rat with epidural stimulation.
Neuroscience letters, 2008Co-Authors: Ronaldo M. Ichiyama, Roland R. Roy, Yury Gerasimenko, Hui Zhong, Devin L. Jindrich, V. Reggie EdgertonAbstract:Epidural electrical stimulation (ES) at spinal cord segment L2 can produce coordinated step-like movements in completely spinalized adult rats [R.M. Ichiyama, Y.P. Gerasimenko, H. Zhong, R.R. Roy, V.R. Edgerton, Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation, Neurosci. Lett. 383 (2005) 339–344]. Plantar placement of the paws, however, was rarely observed. Here, we sought to determine the dose dependence of a 5-HT agonist (Quipazine) on stepping kinematics when administered in combination with ES. Six adult female Sprague–Dawley rats received a complete mid-thoracic spinal cord transection and were implanted with epidural electrodes at the L2 spinal cord level. Quipazine (i.p.) was tested at doses of 0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg. Rats were placed in a body weight support system, allowing them to walk bipedally on a moving treadmill belt (7 cm/s). 3D step kinematics analysis revealed that coordinated alternating bilateral stepping was induced by L2 stimulation (50 Hz) alone and by Quipazine alone. Furthermore, the combination treatment produced significantly greater numbers of plantar steps and improved quality of stepping compared to either intervention alone. Both number and quality of stepping peaked at the intermediate dose of 0.3–0.4 mg/kg. The results indicate that Quipazine and ES can have complementary effects on spinal circuits and that Quipazine dosage is an important factor in differentially modulating these circuitries to improve the quality of the bipedal stepping on a treadmill belt.
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Epidural spinal cord stimulation plus Quipazine administration enable stepping in complete spinal adult rats
Journal of neurophysiology, 2007Co-Authors: Yury Gerasimenko, Roland R. Roy, Ronaldo M. Ichiyama, Igor Lavrov, Grégoire Courtine, Lance Cai, Hui Zhong, V. Reggie EdgertonAbstract:We hypothesized that epidural spinal cord stimulation (ES) and Quipazine (a serotonergic agonist) modulates the excitability of flexor and extensor related intraspinal neural networks in qualitatively unique, but complementary, ways to facilitate locomotion in spinal cord-injured rats. To test this hypothesis, we stimulated (40 Hz) the S(1) spinal segment before and after Quipazine administration (0.3 mg/kg, ip) in bipedally step-trained and nontrained, adult, complete spinal (mid-thoracic) rats. The stepping pattern of these rats was compared with control rats. At the stimulation levels used, stepping was elicited only when the hindlimbs were placed on a moving treadmill. In nontrained rats, the stepping induced by ES and Quipazine administration was non-weight bearing, and the cycle period was shorter than in controls. In contrast, the stepping induced by ES and Quipazine in step-trained rats was highly coordinated with clear plantar foot placement and partial weight bearing. The effect of ES and Quipazine on EMG burst amplitude and duration was greater in flexor than extensor motor pools. Using fast Fourier transformation analysis of EMG bursts during ES, we observed one dominant peak at 40 Hz in the medial gastrocnemius (ankle extensor), whereas there was less of dominant spectral peak in the tibialis anterior (ankle flexor). We suggest that these frequency distributions reflect amplitude modulation of predominantly monosynaptic potentials in the extensor and predominantly polysynaptic pathways in the flexor muscle. Quipazine potentiated the amplitude of these responses. The data suggest that there are fundamental differences in the circuitry that generates flexion and extension during locomotion.
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Spinal cord-transected mice learn to step in response to Quipazine treatment and robotic training.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005Co-Authors: Andy J. Fong, L.l. Cai, Chad K. Otoshi, David J. Reinkensmeyer, Joel W. Burdick, Roland R. Roy, V. Reggie EdgertonAbstract:In the present study, concurrent treatment with robotic step training and a serotonin agonist, Quipazine, generated significant recovery of locomotor function in complete spinal cord-transected mice (T7–T9) that otherwise could not step. The extent of recovery achieved when these treatments were combined exceeded that obtained when either treatment was applied independently. We quantitatively analyzed the stepping characteristics of spinal mice after alternatively administering no training, manual training, robotic training, Quipazine treatment, or a combination of robotic training with Quipazine treatment, to examine the mechanisms by which training and Quipazine treatment promote functional recovery. Using fast Fourier transform and principal components analysis, significant improvements in the step rhythm, step shape consistency, and number of weight-bearing steps were observed in robotically trained compared with manually trained or nontrained mice. In contrast, manual training had no effect on stepping performance, yielding no improvement compared with nontrained mice. Daily bolus Quipazine treatment acutely improved the step shape consistency and number of steps executed by both robotically trained and nontrained mice, but these improvements did not persist after Quipazine was withdrawn. At the dosage used (0.5 mg/kg body weight), Quipazine appeared to facilitate, rather than directly generate, stepping, by enabling the spinal cord neural circuitry to process specific patterns of sensory information associated with weight-bearing stepping. Via this mechanism, Quipazine treatment enhanced kinematically appropriate robotic training. When administered intermittently during an extended period of robotic training, Quipazine revealed training-induced stepping improvements that were masked in the absence of the pharmacological treatment.
