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Journal of Neurophysiology Feb 2018Coordination of respiratory pump and valve muscle activity is essential for normal breathing. A hallmark respiratory response to hypercapnia and hypoxia is the emergence...
Coordination of respiratory pump and valve muscle activity is essential for normal breathing. A hallmark respiratory response to hypercapnia and hypoxia is the emergence of active exhalation, characterized by abdominal muscle pumping during the late one-third of expiration (late-E phase). Late-E abdominal activity during hypercapnia has been attributed to the activation of expiratory neurons located within the parafacial respiratory group (pFRG). However, the mechanisms that control emergence of active exhalation, and its silencing in restful breathing, are not completely understood. We hypothesized that inputs from the Kölliker-Fuse nucleus (KF) control the emergence of late-E activity during hypercapnia. Previously, we reported that reversible inhibition of the KF reduced postinspiratory (post-I) motor output to laryngeal adductor muscles and brought forward the onset of hypercapnia-induced late-E abdominal activity. Here we explored the contribution of the KF for late-E abdominal recruitment during hypercapnia by pharmacologically disinhibiting the KF in in situ decerebrate arterially perfused rat preparations. These data were combined with previous results and incorporated into a computational model of the respiratory central pattern generator. Disinhibition of the KF through local parenchymal microinjections of gabazine (GABA receptor antagonist) prolonged vagal post-I activity and inhibited late-E abdominal output during hypercapnia. In silico, we reproduced this behavior and predicted a mechanism in which the KF provides excitatory drive to post-I inhibitory neurons, which in turn inhibit late-E neurons of the pFRG. Although the exact mechanism proposed by the model requires testing, our data confirm that the KF modulates the formation of late-E abdominal activity during hypercapnia. NEW & NOTEWORTHY The pons is essential for the formation of the three-phase respiratory pattern, controlling the inspiratory-expiratory phase transition. We provide functional evidence of a novel role for the Kölliker-Fuse nucleus (KF) controlling the emergence of abdominal expiratory bursts during active expiration. A computational model of the respiratory central pattern generator predicts a possible mechanism by which the KF interacts indirectly with the parafacial respiratory group and exerts an inhibitory effect on the expiratory conditional oscillator.
Topics: Animals; Central Pattern Generators; Evoked Potentials, Motor; Hypercapnia; Kolliker-Fuse Nucleus; Male; Models, Neurological; Peripheral Nerves; Rats; Rats, Wistar; Respiration; Respiratory Muscles
PubMed: 29070631
DOI: 10.1152/jn.00499.2017 -
Journal of Neurophysiology Aug 2014Regulation of feeding behavior involves the integration of multiple physiological and neurological pathways that control both nutrient-seeking and consummatory...
Regulation of feeding behavior involves the integration of multiple physiological and neurological pathways that control both nutrient-seeking and consummatory behaviors. The consummatory phase of ingestion includes stereotyped oromotor movements of the tongue and jaw that are controlled through brain stem pathways. These pathways encompass not only cranial nerve sensory and motor nuclei for processing feeding-related afferent signals and supplying the oromotor musculature but also reticular neurons for orchestrating ingestion and coordinating it with other behaviors that utilize the same musculature. Based on decerebrate studies, this circuit should be sensitive to satiety mechanisms mediated centrally by A2 noradrenergic neurons in the caudal nucleus of the solitary tract (cNST) that are potently activated during satiety. Because the first observable phase of satiety is inhibition of oromotor movements, we hypothesized that norepinephrine (NE) would act to inhibit prehypoglossal neurons in the medullary reticular formation. Using patch-clamp electrophysiology of retrogradely labeled prehypoglossal neurons and calcium imaging to test this hypothesis, we demonstrate that norepinephrine can influence both pre- and postsynaptic properties of reticular neurons through both α1- and α2-adrenoreceptors. The α1-adrenoreceptor agonist phenylephrine (PE) activated an inward current in the presence of TTX and increased the frequency of both inhibitory and excitatory miniature postsynaptic currents. The α2-adrenoreceptor agonist dexmedetomidine (DMT) inhibited cNST-evoked excitatory currents as well as spontaneous and miniature excitatory currents through presynaptic mechanisms. The diversity of adrenoreceptor modulation of these prehypoglossal neurons may reflect their role in a multifunctional circuit coordinating both ingestive and respiratory lingual function.
Topics: Animals; Calcium; Excitatory Postsynaptic Potentials; Inhibitory Postsynaptic Potentials; Medulla Oblongata; Miniature Postsynaptic Potentials; Motor Activity; Mouth; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Neurons; Norepinephrine; Patch-Clamp Techniques; Presynaptic Terminals; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, alpha-2; Tissue Culture Techniques
PubMed: 24805080
DOI: 10.1152/jn.00091.2014 -
Respiratory Physiology & Neurobiology Aug 2015Respiration consists of three phases--inspiration (I), post-inspiration (post-I), and late expiration (E2). Pre-I is a subphase occurring at the end of E2. Hypoglossal...
Respiration consists of three phases--inspiration (I), post-inspiration (post-I), and late expiration (E2). Pre-I is a subphase occurring at the end of E2. Hypoglossal (XII) discharge contains I and occasionally pre-I activity. Functionally, XII pre-I underlies tongue muscle contraction and expansion of the upper airway, causing a decrease in airway resistance in anticipation of the succeeding inspiratory effort. It has been shown that vagotomy causes an increase in pre-I activity in XII in anesthetized animals. Also, in anesthetized artificially-ventilated animals, XII onset is synchronized with that of inspiratory phrenic nerve (PhN) activity. Therefore, we sought to systematically test the hypothesis that XII pre-I is present in vagus-intact unanesthetized decerebrate animals and vagal afferents negatively modulate XII pre-I discharge in decerebrate rats, in the absence of confounding anesthesia. Experiments were performed on seven Sprague-Dawley unanesthetized decerebrate adult male rats and bilateral PhN and XII recordings performed. In three animals, vagotomy was performed during PhN recordings and one animal was vagotomized during initial surgical preparation prior to recordings. In vagus-intact animals, XII pre-I duration averaged 12.4 ms. Vagotomy was associated with greater XII pre-I duration, expressed in absolute time (89.5 vs. 12.4 ms; p<0.01) as well as relative to the XII bursting period (18.9 vs. 3.4%; p<0.01). Vagal deafferentation was also associated with a larger relative amplitude of the pre-I XII activity relative to total XII discharge (12.4 vs. 2.1%; p<0.01). We conclude that pre-I discharge is present in vagus-intact artificially-ventilated unanesthetized decerebrate animals and is negatively modulated by vagal afferents.
Topics: Action Potentials; Animals; Decerebrate State; Hypoglossal Nerve; Male; Phrenic Nerve; Rats; Rats, Sprague-Dawley; Respiration; Vagotomy; Vagus Nerve
PubMed: 25979456
DOI: 10.1016/j.resp.2015.05.002 -
Undersea & Hyperbaric Medicine :... 2021Paroxysmal autonomic instability syndrome with dystonia (PAISD) is a possible complication that worsens the prognosis of hypoxic-ischemic encephalopathy related to...
Paroxysmal autonomic instability syndrome with dystonia (PAISD) is a possible complication that worsens the prognosis of hypoxic-ischemic encephalopathy related to non-fatal drowning. There are case reports of hyperbaric oxygen (HBO2) therapy enhancing recovery in such cases. We report a case of a 5-year-old boy admitted to the Pediatric Intensive Care Unit after a non-fatal drowning. He was transferred under mechanical ventilation and sedation, with hemodynamic instability and hypothermia. On admission he had a Glasgow Coma Score of 6. On the fifth day of admission he presented episodes of dystonia with decerebration posture, diaphoresis, tachycardia and hypertension, sometimes with identified triggers, suggesting PAISD. The episodes were difficult to control; multiple drugs were needed. Electroencephalography showed diffuse slow wave activity, and cranioencephalic magnetic resonance imaging showed hypoxia-related lesions, suggesting hypoxic-ischemic encephalopathy. Early after admission the patient started physiotherapy combined with normobaric oxygen therapy. Subsequently he started HBO2 therapy at 2 atmospheres, with a total of 66 sessions. Dystonia progressively subsided, with gradual discontinuation of therapy. He also showed improvement in spasticity, non-verbal communication and cephalic control. This case highlights the diagnostic and therapeutic challenges of PAISD and the potential benefit of HBO2 therapy, even in the subacute phase, in recovery of hypoxic-ischemic encephalopathy.
Topics: Child, Preschool; Decerebrate State; Drowning; Dystonia; Humans; Hyperbaric Oxygenation; Hypoxia-Ischemia, Brain; Male; Physical Therapy Modalities
PubMed: 33648033
DOI: 10.22462/01.03.2021.6 -
Neurourology and Urodynamics Nov 2018Sacral spinal cord injury (SCI) could induce underactive bladder (UAB). Malfunction of connexin 43 (CX43) regulated by TGF-β1 might involve in urinary bladder...
AIMS
Sacral spinal cord injury (SCI) could induce underactive bladder (UAB). Malfunction of connexin 43 (CX43) regulated by TGF-β1 might involve in urinary bladder dysfunction. We studied the changes of CX43 and TGF-β1/Smad3 signaling in detrusor of neurogenic bladder (NB) in sacral SCI rats.
METHODS
Sacral SCI was produced by hemisection (SSCH) or transection (SSCT) of spinal cord between L4 and L5 in female Wistar rats. BBB scores, residual urine volume and bladder weight as well as characteristic cystometric parameters at 6th week were used to confirm the successful establishment of NB. Western blotting and qRT-PCR were used to exam the protein and mRNA expression levels of CX43, CX45, TGF-β1, and Smad3 in detrusor.
RESULTS
BBB scores were significantly decreased, with the lowest in SSCT rats (P < 0.01). The residual urine volume, mean bladder weight, and cystometric parameters were increased, with the highest in SSCT rats. CX43 and phospho-CX43 protein levels were significantly decreased, but those of TGF-β1, Smad3, and phospho-Smad3 were significantly increased. It was the protein and mRNA levels of CX43 but not those of CX45 which were decreased in negative accordance with those of TGF-β1 and Smad3. Those changes were more significant in SSCT than in SSCH rats.
CONCLUSIONS
This study indicates that voiding dysfunction is related to the decreased CX43 function in detrusor from NB. TGF-β1/Smad3 signaling might be involved in the down-regulation of CX43 in SCI rats. Early regulation of CX43 might be beneficial to patients with voiding dysfunction.
Topics: Animals; Connexin 43; Decerebrate State; Female; Organ Size; Rats; Rats, Wistar; Smad3 Protein; Spinal Cord Injuries; Transforming Growth Factor beta1; Urinary Bladder; Urinary Bladder, Neurogenic; Urodynamics
PubMed: 30070388
DOI: 10.1002/nau.23767 -
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 -
Neuroscience Feb 2017The ventromedial hypothalamus (VMH) is known to play an important role in feeding behavior and the control of sympathetic nerve activity (SNA). We report the...
The ventromedial hypothalamus (VMH) is known to play an important role in feeding behavior and the control of sympathetic nerve activity (SNA). We report the identification of novel neuron groups that showed oscillations on both sides of the VMH in hypothalamus slice preparations from juvenile rats of postnatal days 5-14. We detected spontaneous rhythmic burst activity with a frequency of around 0.06Hz typically in the dorsolateral region of the VMH (i.e., VMH oscillation) using optical recordings (voltage and calcium imaging), field potential recordings and intracellular membrane potential recordings. The oscillation was also confirmed after isolation of the VMH from other hypothalamic structures. The frequency of oscillation was increased by lowering the glucose concentration of the superfusate. To evaluate the relation between VMH oscillation and SNA, we simultaneously recorded VMH oscillation, SNA from the thoracic sympathetic nerve trunk and phrenic nerve discharge (Phr) in the decerebrate and arterially perfused in situ preparation from juvenile rats of postnatal days 5-11. Power spectral analysis in the arterially perfused in situ rat preparation revealed similar peak values to those of slice preparations within the low-frequency range between the VMH oscillation and sympathetic nerve trunk activity. In addition, we analyzed cross-correlations between the VMH, SNA and Phr. The results revealed that a predominant positive correlation of the VMH activity with the SNA existed with an average time lag of 2.4s, suggesting the presence of functional couplings between the VMH and SNA (and respiratory center) in the lower brainstem and spinal cord. We hypothesize that the VMH oscillation might be involved in low-frequency modulation of the SNA.
Topics: Action Potentials; Animals; Calcium; Decerebrate State; Glucose; Hypothalamus, Middle; Microelectrodes; Periodicity; Rats, Wistar; Sympathetic Nervous System; Tissue Culture Techniques; Voltage-Sensitive Dye Imaging
PubMed: 27956062
DOI: 10.1016/j.neuroscience.2016.11.048