-
Neuroscience Dec 2020Sensory information arising from limb movements controls the spinal locomotor circuitry to adapt the motor pattern to demands of the environment. Stimulation of extensor...
Sensory information arising from limb movements controls the spinal locomotor circuitry to adapt the motor pattern to demands of the environment. Stimulation of extensor group (gr) I afferents during fictive locomotion in decerebrate cats prolongs the ongoing extension, and terminates ongoing flexion with an initiation of the subsequent extension, i. e. "resetting to extension". Moreover, instead of the classical Ib non-reciprocal inhibition, stimulation of extensor gr I afferents produces a polysynaptic excitation in extensor motoneurons with latencies (∼3.5-4.0 ms) compatible with 3 interposed interneurons. We assume that some interneurons in this pathway actually belong to the rhythm-generating layer of the locomotor Central Pattern Generator (CPG), since their activity was correlated to a resetting of the rhythm. In the present work fictive locomotion was (mostly) induced by i.v. injection of nialamide followed by l-DOPA in paralyzed cats following decerebration and spinalization at C1 level. In some experiments, we extended previous observations during fictive locomotion on the emergence and locomotor state-dependence of polysynaptic excitatory postsynaptic potentials from extensor gr I afferents to ankle extensor motoneurons. However, the main focus was to record location and properties of interneurons (n = 62) that (i) were active during the extensor phase of fictive locomotion and (ii) received short-latency excitation (mono-, di- or polysynaptic) from extensor gr I afferents. We conclude that the interneurons recorded fulfill the characteristics to belong to the neuronal pathway activated by extensor gr I afferents during locomotion, and may contribute to the 'resetting to extension' as part of the locomotor CPG.
Topics: Animals; Cats; Decerebrate State; Electric Stimulation; Excitatory Postsynaptic Potentials; Interneurons; Locomotion; Motor Neurons; Spinal Cord
PubMed: 32946952
DOI: 10.1016/j.neuroscience.2020.09.017 -
Autonomic Neuroscience : Basic &... Jul 2022Our understanding of central nervous system regulation of the set-point of arterial pressure remains incomplete, especially in conditions of hypertension. The...
Our understanding of central nervous system regulation of the set-point of arterial pressure remains incomplete, especially in conditions of hypertension. The ventrolateral periaqueductal gray (vlPAG) is of particular interest given that its acute activation induces hypotension and sympatho-inhibition in anaesthetised, normotensive animals, and recent preliminary studies have shown that vlPAG stimulation can reduce blood pressure in refractory hypertensive patients. To assist our mechanistic understanding, we investigated whether electrical stimulation of the vlPAG had depressor actions in a model of neurogenic hypertension, the spontaneously hypertensive (SH) rat. We found that electrical stimulation of the lateral and vlPAG (2-6 V, 20-40 Hz, 0.18-0.2 ms pulse width) decreased arterial pressure (-19 ± 4 mm Hg, n = 8) and heart rate (median - 18 bpm) in anaesthetised SH rats. In contrast, in conscious freely-moving SH rats fitted with blood pressure telemetry, stimulation of this same region produced failed to evoked a hypotensive response (n = 13; either no change, n = 9; or an increase in arterial pressure of 23 ± 4 mm Hg, n = 4). The hypotensive action of the vlPAG observed in anaesthetised animals has been attributed to inhibition of pre-sympathetic neurones originating in the rostral ventrolateral medulla. We therefore used an un-anaesthetised, decerebrate SH rat preparation to investigate whether activation of vlPAG neurons produced sympatho-inhibition that might be below the threshold at which a peripheral vascular response could be observed. Only sympatho-excitatory responses to electrical and excitatory amino acid microinjections were observed, and these were evoked from both the dorsal and ventral PAG; no responses were evoked from the vlPAG. We conclude that the vlPAG is not a reliable antihypertensive locus in the awake SH rat. We discuss the potential importance of the state-dependency of the hypotensive response that can be evoked from the vlPAG, which has important implications for translating to humans.
Topics: Animals; Arterial Pressure; Blood Pressure; Humans; Hypertension; Hypotension; Microinjections; Periaqueductal Gray; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley
PubMed: 35526354
DOI: 10.1016/j.autneu.2022.102984 -
Brain Research Feb 2020Central command, a feedforward signal from higher brain centers, regulates the cardiovascular system in association with exercise. Previous evidence suggests that...
Central command, a feedforward signal from higher brain centers, regulates the cardiovascular system in association with exercise. Previous evidence suggests that nucleus (or nuclei) around the midbrain may contribute to generating spontaneous motor activity and concomitant cardiovascular responses. To examine which area within the midbrain is important for the spontaneous and synchronized responses, 18 rats were decerebrated at three levels (pre-midbrain, rostroventral midbrain, and caudal midbrain levels) and paralyzed with a neuromuscular blocker. Individual brain sections showed decerebration rostral to the pre-collicular level in the pre-midbrain preparation and, additionally, removal of the periaqueductal gray in the rostroventral midbrain preparation, and decerebration around the midcollicular level in the caudal midbrain preparation. Spontaneous motor activity occurred at frequency of 69 ± 27 times/h and accompanied increases in heart rate (by 15 ± 4 beats/min) and mean arterial blood pressure (by 54 ± 4 mmHg) in the pre-midbrain preparation. Similar motor and cardiovascular responses took place in the rostroventral midbrain preparation, while such responses hardly occurred in the caudal midbrain preparation. We next examined whether injection of a GABAergic receptor agonist (muscimol) in the ventral tegmental area (VTA) inhibits the spontaneous motor and cardiovascular responses in 6 pre-midbrain preparations. The occurrence of spontaneous motor activity and concomitant cardiovascular responses was inhibited clearly (P < 0.05) by injection of muscimol, but not saline. It is concluded that the VTA plays a pivotal role in the spontaneous and synchronized activation of the motor and cardiovascular systems in decerebrate rats.
Topics: Animals; Cardiovascular Physiological Phenomena; Decerebrate State; Male; Motor Activity; Rats; Rats, Wistar; Ventral Tegmental Area
PubMed: 31863729
DOI: 10.1016/j.brainres.2019.146616 -
Experimental Neurology Oct 2019It has been established that stepping of the decerebrate cat was accompanied by involvement of the urinary system: external urethral sphincter (EUS) and detrusor muscle...
It has been established that stepping of the decerebrate cat was accompanied by involvement of the urinary system: external urethral sphincter (EUS) and detrusor muscle activation, as well as the corresponding increase of the intravesical pressure. Detrusor and EUS evoked EMG activity matched the limbs locomotor movements. Immunohistochemical labeling of the immediate early gene c-fos expression was used to reveal the neural mechanisms of such somatovisceral interconnection within the sacral neural pathways. Study showed that two locomotor modes (forward and backward walking) had significantly different kinematic features. Combining the different immunohistochemical methods, we found that many c-fos-immunopositive nuclei were localized within several visceral areas of the S2 spinal segment which matched the sacral parasympathetic nucleus and dorsal gray commissure. Cats stepping backward had 4-fold more c-fos-immunopositive nuclei within the ventrolateral part of the sacral parasympathetic nucleus apparently correspondent to the "lateral band" contained cells controlling bladder function. The present work provides the direct evidences of visceral neurons activation depending on the specific of locomotor pattern and confirms the somatovisceral integration carrying out on the spinal cord level.
Topics: Animals; Cats; Decerebrate State; Female; Locomotion; Male; Neural Pathways; Parasympathetic Nervous System; Spinal Cord; Urinary Bladder; Urinary Tract Physiological Phenomena
PubMed: 31254518
DOI: 10.1016/j.expneurol.2019.112986 -
Physiological Reports Sep 2021Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fiber muscle afferents and produce reflex increases in...
Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fiber muscle afferents and produce reflex increases in sympathetic nerve activity and blood pressure during exercise (i.e., the exercise pressor reflex; EPR). The EPR is exaggerated in patients and animals with heart failure with reduced ejection fraction (HF-rEF) and its activation contributes to reduced exercise capacity within this patient population. Accumulating evidence suggests that the exaggerated EPR in HF-rEF is partially attributable to a sensitization of mechanically activated channels produced by thromboxane A receptors (TxA -Rs) on those sensory endings; however, this has not been investigated. Accordingly, the purpose of this investigation was to determine the role played by TxA -Rs on the sensory endings of thin fiber muscle afferents in the exaggerated EPR in rats with HF-rEF induced by coronary artery ligation. In decerebrate, unanesthetized rats, we found that injection of the TxA -R antagonist daltroban (80 μg) into the arterial supply of the hindlimb reduced the pressor response to 30 s of electrically induced 1 Hz dynamic hindlimb muscle contraction in HF-rEF (n = 8, peak ∆MAP pre: 22 ± 3; post: 14 ± 2 mmHg; p = 0.01) but not sham (n = 10, peak ∆MAP pre: 13 ± 3; post: 11 ± 2 mmHg; p = 0.68) rats. In a separate group of HF-rEF rats (n = 4), we found that the systemic (intravenous) injection of daltroban had no effect on the EPR (peak ΔMAP pre: 26 ± 7; post: 25 ± 7 mmHg; p = 0.50). Our data suggest that TxA -Rs on thin fiber muscle afferents contribute to the exaggerated EPR evoked in response to dynamic muscle contraction in HF-rEF.
Topics: Animals; Blood Pressure; Heart Failure; Male; Motor Activity; Muscle Contraction; Muscle, Skeletal; Nerve Endings; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane A2, Prostaglandin H2; Reflex; Sensory Receptor Cells
PubMed: 34558221
DOI: 10.14814/phy2.15052 -
Brain Communications 2020Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a...
Mechanisms of motor deficits (e.g. hemiparesis and hemiplegia) secondary to stroke and traumatic brain injury remain poorly understood. In early animal studies, a unilateral lesion to the cerebellum produced postural asymmetry with ipsilateral hindlimb flexion that was retained after complete spinal cord transection. Here we demonstrate that hindlimb postural asymmetry in rats is induced by a unilateral injury of the hindlimb sensorimotor cortex, and characterize this phenomenon as a model of spinal neuroplasticity underlying asymmetric motor deficits. After cortical lesion, the asymmetry was developed due to the contralesional hindlimb flexion and persisted after decerebration and complete spinal cord transection. The asymmetry induced by the left-side brain injury was eliminated by bilateral lumbar dorsal rhizotomy, but surprisingly, the asymmetry after the right-side brain lesion was resistant to deafferentation. Pancuronium, a curare-mimetic muscle relaxant, abolished the asymmetry after the right-side lesion suggesting its dependence on the efferent drive. The contra- and ipsilesional hindlimbs displayed different musculo-articular resistance to stretch after the left but not right-side injury. The nociceptive withdrawal reflexes evoked by electrical stimulation and recorded with EMG technique were different between the left and right hindlimbs in the spinalized decerebrate rats. On this asymmetric background, a brain injury resulted in greater reflex activation on the contra- versus ipsilesional side; the difference between the limbs was higher after the right-side brain lesion. The unilateral brain injury modified expression of neuroplasticity genes analysed as readout of plastic changes, as well as robustly impaired coordination of their expression within and between the ipsi- and contralesional halves of lumbar spinal cord; the effects were more pronounced after the left side compared to the right-side injury. Our data suggest that changes in the hindlimb posture, resistance to stretch and nociceptive withdrawal reflexes are encoded by neuroplastic processes in lumbar spinal circuits induced by a unilateral brain injury. Two mechanisms, one dependent on and one independent of afferent input may mediate asymmetric hindlimb motor responses. The latter, deafferentation resistant mechanism may be based on sustained muscle contractions which often occur in patients with central lesions and which are not evoked by afferent stimulation. The unusual feature of these mechanisms is their lateralization in the spinal cord.
PubMed: 32954305
DOI: 10.1093/braincomms/fcaa055 -
American Journal of Physiology.... Nov 2019The exercise pressor reflex is initiated by the contraction-induced activation of group III and IV muscle afferents. The reflex is manifested by increases in arterial...
The exercise pressor reflex is initiated by the contraction-induced activation of group III and IV muscle afferents. The reflex is manifested by increases in arterial blood pressure and cardiac output, which, in turn, are generated by increases in the sympathetic outflow to the heart and vasculature and decreases in the vagal outflow to the heart. In previous experiments, we used a pharmacological approach to assess the role played by the acid-sensing ion channel 3 (ASIC3) on group III and IV afferents in evoking the exercise pressor reflex. In the present experiments, we used an alternative approach, namely functional knockout (KO) of the ASIC3 gene, to confirm and extend our previous finding that pharmacological blockade of the ASIC3 had only a small impact on the expression of the exercise pressor reflex when the arterial supply to the contracting hindlimb muscles of rats was patent. Using this alternative approach, we compared the magnitude of the exercise pressor reflex evoked in ASIC3 KO rats with that evoked in their wild-type (WT) counterparts. We found both WT and ASIC3 KO rats displayed similar pressor responses to static contraction (WT, = 10, +12 ± 2 mmHg; KO, = 9, +11 ± 2 mmHg) and calcaneal tendon stretch (WT, = 9, +13 ± 2 mmHg; KO, = 7, +11 ± 2 mmHg). Likewise, both WT and ASIC3 KO displayed similar pressor responses to intra-arterial injection of 12 mM lactic acid (WT, = 9, +14 ± 3 mmHg; KO, = 8, +18 ± 5 mmHg), 24 mM lactic acid (WT, = 9,+24 ± 2 mmHg; KO, = 8, +20 ± 5 mmHg), capsaicin (WT, = 9,+27 ± 5 mmHg; KO, = 10, +29 ± 5 mmHg), and diprotonated phosphate ([Formula: see text]; WT, = 6,+22 ± 3 mmHg; KO, = 6, +32 ± 6 mmHg). We conclude that redundant receptors are responsible for evoking the pressor reflexes arising from group III and IV afferents.
Topics: Acid Sensing Ion Channels; Animals; Decerebrate State; Lower Extremity; Muscle Contraction; Muscle, Skeletal; Physical Conditioning, Animal; Physical Exertion; Rats; Rats, Sprague-Dawley; Reflex
PubMed: 31347922
DOI: 10.1152/ajpregu.00148.2019 -
Experimental Brain Research Sep 2021Successful propagation throughout the step cycle is contingent on adequate regulation of whole-limb stiffness by proprioceptive feedback. Following spinal cord injury...
Successful propagation throughout the step cycle is contingent on adequate regulation of whole-limb stiffness by proprioceptive feedback. Following spinal cord injury (SCI), there are changes in the strength and organization of proprioceptive feedback that can result in altered joint stiffness. In this study, we measured changes in autogenic feedback of five hindlimb extensor muscles following chronic low thoracic lateral hemisection (LSH) in decerebrate cats. We present three features of the autogenic stretch reflex obtained using a mechanographic method. Stiffness was a measure of the resistance to stretch during the length change. The dynamic index documented the extent of adaptation or increase of the force response during the hold phase, and the impulse measured the integral of the response from initiation of a stretch to the return to the initial length. The changes took the form of variable and transient increases in the stiffness of vastus (VASTI) group, soleus (SOL), and flexor hallucis longus (FHL), and either increased (VASTI) or decreased adaptation (GAS and PLANT). The stiffness of the gastrocnemius group (GAS) was also variable over time but remained elevated at the final time point. An unexpected finding was that these effects were observed bilaterally. Potential reasons for this finding and possible sources of increased excitability to this muscle group are discussed.
Topics: Animals; Decerebrate State; Hindlimb; Muscle, Skeletal; Reflex; Reflex, Stretch; Spinal Cord Injuries; Up-Regulation
PubMed: 34218298
DOI: 10.1007/s00221-020-06016-1 -
Experimental Physiology Nov 2020What is the central question of this study? Do endoperoxide 4 and thromboxane A receptors, which are receptors for cyclooxygenase products of arachidonic metabolism, on...
NEW FINDINGS
What is the central question of this study? Do endoperoxide 4 and thromboxane A receptors, which are receptors for cyclooxygenase products of arachidonic metabolism, on thin fibre muscle afferents play a role in the chronic mechanoreflex sensitization present in rats with heart failure with reduced ejection fraction (HF-rEF)? What is the main finding and its importance? The data do not support a role for endoperoxide 4 receptors or thromboxane A receptors in the chronic mechanoreflex sensitization in HF-rEF rats.
ABSTRACT
We investigated the role of cyclooxygenase metabolite-associated endoperoxide 4 receptors (EP4-R) and thromboxane A receptors (TxA -R) on thin fibre muscle afferents in the chronic mechanoreflex sensitization in rats with myocardial infarction-induced heart failure with reduced ejection fraction (HF-rEF). We hypothesized that injection of either the EP4-R antagonist L-161,982 (1 µg) or the TxA -R antagonist daltroban (80 µg) into the arterial supply of the hindlimb would reduce the increase in blood pressure and renal sympathetic nerve activity (RSNA) evoked in response to 30 s of static hindlimb skeletal muscle stretch (a model of isolated mechanoreflex activation) in decerebrate, unanaesthetized HF-rEF rats but not sham-operated control rats (SHAM). Ejection fraction was significantly reduced in HF-rEF (45 ± 11%) compared to SHAM (83 ± 6%; P < 0.01) rats. In SHAM and HF-rEF rats, we found that the EP4-R antagonist had no effect on the peak increase in mean arterial pressure (peak ΔMAP SHAM n = 6, pre: 15 ± 7, post: 15 ± 9, P = 0.99; HF-rEF n = 9, pre: 30 ± 11, post: 32 ± 15 mmHg, P = 0.84) or peak increase in RSNA (peak ΔRSNA SHAM pre: 33 ± 14, post: 47 ± 31%, P = 0.94; HF-rEF, pre: 109 ± 47, post: 139 ± 150%, P = 0.76) response to stretch. Similarly, in SHAM and HF-rEF rats, we found that the TxA -R antagonist had no effect on the peak ΔMAP (SHAM n = 7, pre: 13 ± 7, post: 19 ± 14, P = 0.15; HF-rEF n = 14, pre: 24 ± 13, post: 21 ± 13 mmHg, P = 0.47) or peak ΔRSNA (SHAM pre: 52 ± 43, post: 57 ± 67%, P = 0.94; HF-rEF, pre: 108 ± 93, post: 88 ± 72%, P = 0.30) response to stretch. The data do not support a role for EP4-Rs or TxA -Rs in the chronic mechanoreflex sensitization in HF-rEF.
Topics: Animals; Blood Pressure; Heart Failure; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane; Reflex; Thromboxanes
PubMed: 32954541
DOI: 10.1113/EP088835 -
American Journal of Physiology.... Sep 2019Passive limb movement and limb muscle stretch in humans and animals are common experimental strategies used to investigate activation of the muscle mechanoreflex...
Passive limb movement and limb muscle stretch in humans and animals are common experimental strategies used to investigate activation of the muscle mechanoreflex independent of contraction-induced metabolite production. Cyclooxygenase (COX) metabolites, however, are produced by skeletal muscle stretch in vitro and have been found to impact various models of mechanoreflex activation. Whether COX metabolites influence the decerebrate rat triceps surae muscle stretch mechanoreflex model remains unknown. We examined the effect of rat triceps surae muscle stretch on the interstitial concentration of the COX metabolite prostaglandin E (PGE). Interstitial PGE concentration was increased above baseline values by 4 min of both static (38% increase, = 0.01) and dynamic (56% increase, < 0.01) triceps surae muscle stretch ( = 10). The 4-min protocol was required to collect enough microdialysis fluid for PGE detection. The finding that skeletal muscle stretch in vivo was capable of producing COX metabolites prompted the hypothesis that intra-arterial administration of the COX inhibitor indomethacin (1 mg/kg) would reduce the pressor and cardioaccelerator responses evoked during 30 s (the duration most commonly used in the rat mechanoreflex model) of static and dynamic rat triceps surae muscle stretch. We found that indomethacin had no effect ( > 0.05, = 9) on the pressor or cardioaccelerator response during 30 s of either static or dynamic stretch. We conclude that, despite the possibility of increased COX metabolite concentration, COX metabolites do not activate or sensitize thin-fiber muscle afferents stimulated during 30 s of static or dynamic hindlimb skeletal muscle stretch in healthy rats.
Topics: Animals; Blood Pressure; Cyclooxygenase Inhibitors; Decerebrate State; Dinoprostone; Heart Rate; Indomethacin; Male; Mechanoreceptors; Rats; Rats, Sprague-Dawley; Reflex, Stretch
PubMed: 31241976
DOI: 10.1152/ajpregu.00080.2019