-
Frontiers in Neural Circuits 2014Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic...
Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a "hyper-cholinergic" state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.
Topics: Animals; Animals, Newborn; Catheters, Indwelling; Cats; Cholinergic Agonists; Cholinergic Antagonists; Decerebrate State; Electrodes, Implanted; Electromyography; Hindlimb; Locomotion; Lumbar Vertebrae; Periodicity; Rats, Sprague-Dawley; Receptors, Cholinergic; Spinal Cord; Spinal Cord Injuries
PubMed: 25414645
DOI: 10.3389/fncir.2014.00132 -
Pediatrics Jan 2017A 14-year-old previously healthy female was transferred from a local emergency department after being found unresponsive at home. Parental questioning revealed she had...
A 14-year-old previously healthy female was transferred from a local emergency department after being found unresponsive at home. Parental questioning revealed she had fever and pharyngitis 2 weeks before presentation. Past mental health history was negative, including concern for past or present suicidal ideation/attempts, suspected substance use, or toxic ingestion. In the emergency department, she was orotracheally intubated due to a Glasgow Coma Scale of 3. She was hemodynamically stable and euglycemic. Electrocardiogram showed sinus tachycardia. She underwent a noncontrast head computed tomography that was normal and subsequently underwent a lumbar puncture. She had a seizure and was given a loading dose of diazepam and fosphenytoin that led to cessation of extremity movements. She was subsequently transferred to the PICU for additional evaluation. Initial examination without sedation or analgesia demonstrated dilated and minimally responsive pupils, intermittent decorticate posturing, and bilateral lower extremity rigidity and clonus, consistent with a Glasgow Coma Scale of 5. Serum studies were unremarkable with the exception of mild leukocytosis. Chest radiograph only showed atelectasis. She was empirically started on antibiotics to cover for meningitis pending final cerebral spinal fluid test results. The pediatric neurology team was consulted for EEG monitoring, and the patient was eventually sent for computed tomography angiogram and magnetic resonance angiogram/venogram. We will review diagnostic evaluation and management of an adolescent patient with acute encephalopathy with decorticate posturing of unclear etiology.
Topics: Acute Febrile Encephalopathy; Adolescent; Amitriptyline; Brain; Bupropion; Decerebrate State; Diagnosis, Differential; Emergency Service, Hospital; Female; Glasgow Coma Scale; Humans; Intensive Care Units, Pediatric; Interdisciplinary Communication; Intersectoral Collaboration; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Self Medication; Serotonin Syndrome; Suicide, Attempted; Tomography, X-Ray Computed; Venlafaxine Hydrochloride
PubMed: 27940505
DOI: 10.1542/peds.2015-3779 -
American Journal of Physiology.... Aug 2014The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n =...
The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa.
Topics: Air; Animals; Cats; Decerebrate State; Electromyography; Eructation; Esophageal Sphincter, Lower; Esophageal Sphincter, Upper; Esophagogastric Junction; Mechanoreceptors; Muscle Relaxation; Pressure; Stomach
PubMed: 24970778
DOI: 10.1152/ajpgi.00120.2014 -
The Journal of Comparative Neurology Jun 2016Neurochemical microstimulation in different parts of the midbrain periaqueductal gray (PAG) in the cat generates four different types of vocalization, mews, howls,...
Neurochemical microstimulation in different parts of the midbrain periaqueductal gray (PAG) in the cat generates four different types of vocalization, mews, howls, cries, and hisses. Mews signify positive vocal expression, whereas howls, hisses, and cries signify negative vocal communications. Mews were generated in the lateral column of the intermediate PAG and howls and hisses in the ventrolateral column of the intermediate PAG. Cries were generated in two regions, the lateral column of the rostral PAG and the ventrolateral column of the caudal PAG. To define the specific motor patterns belonging to mews, howls, and cries, the following muscles were recorded during these vocalizations: larynx (cricothyroid, thyroarytenoid, and posterior cricoarytenoid), tongue (genioglossus), jaw (digastric), and respiration (diaphragm, internal intercostal, external abdominal oblique, and internal abdominal oblique) muscles. Furthermore, the frequency, intensity, activation cascades, and turns and amplitude analyses of the electromyograms (EMGs) during these vocalizations were analyzed. The results show that each type of vocalization consists of a specific, circumscribed motor coordination. The nucleus retroambiguus (NRA) in the caudal medulla serves as the final premotor interneuronal output system for vocalization. NRA neurochemical microstimulation also generated vocalizations (guttural sounds). Analysis of the EMGs demonstrated that these vocalizations consist of only small parts of the emotional voalizations generated by neurochemical stimulation in the PAG. These results demonstrate that motor organization of positive and negative emotional vocal expressions are segregated in the PAG and that the PAG uses the NRA as a tool to gain access to the motoneurons generating vocalization.
Topics: Animals; Cats; Decerebrate State; Emotions; Laryngeal Muscles; Motor Neurons; Periaqueductal Gray; Vocalization, Animal
PubMed: 26235936
DOI: 10.1002/cne.23869 -
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 -
The Journal of Physiology Feb 2016Mechanical and metabolic stimuli from contracting muscles evoke reflex increases in blood pressure, heart rate and sympathetic nerve activity. Little is known, however,...
Mechanical and metabolic stimuli from contracting muscles evoke reflex increases in blood pressure, heart rate and sympathetic nerve activity. Little is known, however, about the nature of the mechano-gated channels on the thin fibre muscle afferents that contribute to evoke this reflex, termed the exercise pressor reflex. We determined the effect of GsMTx4, an inhibitor of mechano-gated Piezo channels, on the exercise pressor reflex evoked by intermittent contraction of the triceps surae muscles in decerebrated, unanaesthetized rats. GsMTx4 reduced the pressor, cardioaccelerator and renal sympathetic nerve responses to intermittent contraction but did not reduce the pressor responses to femoral arterial injection of compounds that stimulate the metabolically-sensitive thin fibre muscle afferents. Expression levels of Piezo2 channels were greater than Piezo1 channels in rat dorsal root ganglia. Our findings suggest that mechanically-sensitive Piezo proteins contribute to the generation of the mechanical component of the exercise pressor reflex in rats. Mechanical and metabolic stimuli within contracting skeletal muscles evoke reflex autonomic and cardiovascular adjustments. In cats and rats, gadolinium has been used to investigate the role played by the mechanical component of this reflex, termed the exercise pressor reflex. Gadolinium, however, has poor selectivity for mechano-gated channels and exerts multiple off-target effects. We tested the hypothesis that GsMTX4, a more selective mechano-gated channel inhibitor than gadolinium and a particularly potent inhibitor of mechano-gated Piezo channels, reduced the exercise pressor reflex in decerebrate rats. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 5, GsMTx4: 12 ± 5 mmHg, P < 0.01), cardioaccelerator and renal sympathetic nerve responses to tendon stretch, a purely mechanical stimulus, but had no effect on the pressor responses to intra-arterial injection of α,β-methylene ATP or lactic acid. Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 2, GsMTx4: 14 ± 3 mmHg, P < 0.01), cardioaccelerator and renal sympathetic nerve responses to electrically-induced intermittent hindlimb muscle contractions. By contrast, injection of 10 μg of GsMTx4 into the jugular vein had no effect on the pressor, cardioaccelerator, or renal sympathetic nerve responses to contraction. Quantitative RT-PCR and western blot analyses indicated that both Piezo1 and Piezo2 channel isoforms were natively expressed in rat dorsal root ganglia tissue. We conclude that GsMTx4 reduced the exercise pressor reflex in decerebrate rats and that the reduction was attributable, at least in part, to its effect on mechano-gated Piezo channels.
Topics: Achilles Tendon; Animals; Decerebrate State; Ganglia, Spinal; Hindlimb; Intercellular Signaling Peptides and Proteins; Ion Channels; Lung; Male; Muscle, Skeletal; Peptides; Physical Conditioning, Animal; Rats, Sprague-Dawley; Reflex; Spider Venoms
PubMed: 26608396
DOI: 10.1113/JP271714 -
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 -
Experimental Neurology Sep 2015Hemisection of the spinal cord at C2 eliminates ipsilateral descending drive to the phrenic nucleus and causes hemidiaphragmatic paralysis in rats. Phrenic nerve (PhN)...
Hemisection of the spinal cord at C2 eliminates ipsilateral descending drive to the phrenic nucleus and causes hemidiaphragmatic paralysis in rats. Phrenic nerve (PhN) or diaphragmatic activity ipsilateral to hemisection can occasionally be induced acutely following hemisection by respiratory stressors (i.e., hypercapnia, asphyxia, contralateral phrenicotomy) and becomes spontaneously active days-to-weeks later. These investigations, however, are potentially confounded by the use of anesthesia, which may suppress spontaneously-active crossed phrenic pathways. Experiments were performed on vecuronium-paralyzed, unanesthetized, decerebrate adult male rats and whole PhN activity recorded continuously before, during, and after high cervical hemisection at the C1 spinal level. Crossed phrenic activity recovered spontaneously over minutes-to-hours with maximal recovery of 11.8 ± 3.1% (m ± SE) in the PhN ipsilateral to hemisection. Additionally, there was a significant increase in PhN activity contralateral to hemisection of 221.0 ± 4 0.4% (m ± SE); since animals were artificially-ventilated, these changes likely represent an increase in central respiratory drive. These results underscore the state-dependence of crossed bulbophrenic projections and suggest that unanesthetized models may be more sensitive in detecting acute recovery of respiratory output following spinal cord injury (SCI). Additionally, our results may suggest an important role for a group of C1-C2 neurons exhibiting respiratory-related activity, spared by the higher level of hemisection. These units may function as relays of polysynaptic bulbophrenic pathways and/or provide excitatory drive to phrenic motoneurons. Our findings provide a new model for investigating acute respiratory recovery following cervical SCI, the high C1-hemisected unanesthetized decerebrate rat and suggest a centrally-mediated increase in central respiratory drive in response to high cervical SCI.
Topics: Action Potentials; Animals; Decerebrate State; Functional Laterality; Laminectomy; Male; Motor Neurons; Neuronal Plasticity; Nonlinear Dynamics; Phrenic Nerve; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries
PubMed: 26056711
DOI: 10.1016/j.expneurol.2015.06.002 -
Neuromodulation : Journal of the... Jun 2024Implantation of stimulating electrodes into the basement of the vertebral spinous process allows the electrodes to be quickly and stably fixed relative to the spinal...
OBJECTIVES
Implantation of stimulating electrodes into the basement of the vertebral spinous process allows the electrodes to be quickly and stably fixed relative to the spinal cord. Using this approach, we have previously shown the selectivity of rat muscle activation during transvertebral stimulation (TS). In this work, we investigated the TS to induce forward stepping of the cat's hindlimbs in comparison with epidural stimulation (ES).
MATERIALS AND METHODS
TS was performed with an electrode placed in the VL3-VL6 vertebrae in five decerebrated cats. ES was performed on the same cats in L5-L7 segments. Kinematic parameters of stepping were recorded in addition to electromyographic activity of musculus (m.) iliopsoas (IP), m. tibialis anterior (TA), and m. gastrocnemius lateralis (GL) of both hindlimbs.
RESULTS
With VL3-VL4 TS, all five animals were capable of bipedal forward stepping, whereas VL5 and VL6 TS led to the forward stepping in 3 of 5 and 1 of 5 animals, respectively. Well-coordinated muscle activity led to a high level of intra- and interlimb coordination. Kinematic parameters of TS-induced stepping were similar to those obtained with ES. The TS of the VL3 vertebra causes the frequency lock with the integer multiple of the stimulation frequency. Similarly to the rat model, TS-evoked muscle responses were site specific. They were minimal during VL3 TS and were maximal during VL4-VL5 TS (IP) and VL5-VL6 TS (TA, GL).
CONCLUSIONS
The obtained results support hypotheses about the location of the central pattern generators in the upper lumbar spinal segments. The proposed approach of electrode placement is surgically easier to perform than is ES. This approach is useful for studying site-specific neuromodulation of the spinal sensorimotor networks and for investigating new strategies of locomotor recovery in animal models.
Topics: Animals; Cats; Decerebrate State; Electromyography; Muscle, Skeletal; Hindlimb; Biomechanical Phenomena; Spinal Cord Stimulation; Electrodes, Implanted; Electric Stimulation; Male; Female; Lumbar Vertebrae
PubMed: 36567242
DOI: 10.1016/j.neurom.2022.11.009 -
Neurourology and Urodynamics Apr 2018To develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro-like access with in...
AIM
To develop the decerebrate arterially perfused mouse (DAPM) preparation, a novel voiding model of the lower urinary tract (LUT) that enables in vitro-like access with in vivo-like neural connectivity.
METHODS
Adult male mice were decerebrated and arterially perfused with a carbogenated, Ringer's solution to establish the DAPM. To allow distinction between central and peripheral actions of interventions, experiments were conducted in both the DAPM and in a "pithed" DAPM which has no brainstem or spinal cord control.
RESULTS
Functional micturition cycles were observed in response to bladder filling. During each void, the bladder showed strong contractions and the external urethral sphincter (EUS) showed bursting activity. Both the frequency and amplitude of non-voiding contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the LUT resulting in retention in DAPM as it increased tonic EUS activity and basal bladder pressure in a dose-dependent manner (basal pressure increase also noted in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion blockade (hexamethonium), initially caused incomplete voiding, and both drugs eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed bladder distention-induced activity in the non-noxious range which was associated with pMM.
CONCLUSIONS
This study demonstrates the utility of the DAPM which allows a detailed characterization of LUT function in mice.
Topics: Animals; Decerebrate State; Electromyography; Female; Male; Mice; Pressure; Urethra; Urinary Bladder; Urination; Urodynamics
PubMed: 29333621
DOI: 10.1002/nau.23471