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The Journal of Physiology Oct 19941. The behaviour of medullary respiratory neurons was studied during fictive coughing and swallowing evoked by electrical stimulation of the superior laryngeal nerve...
1. The behaviour of medullary respiratory neurons was studied during fictive coughing and swallowing evoked by electrical stimulation of the superior laryngeal nerve (SLN) in decerebrate, paralysed and artificially ventilated cats. Fictive coughing, swallowing and respiration were monitored by recording activities of the phrenic, hypoglossal and abdominal nerves. 2. Extracellular recordings were made from respiratory neurons in the ventral respiratory group (VRG) and in the Bötzinger complex (BOT). The neuronal types analysed included decrementing inspiratory neurons (I-DEC), augmenting expiratory neurons (E-AUG) and decrementing expiratory neurons (E-DEC) from the BOT area, and augmenting inspiratory neurons (I-AUG) and augmenting expiratory neurons (E-AUG) from the VRG area. 3. During fictive coughing, all the inspiratory and expiratory neurons were active during the inspiratory and expiratory phases of coughing, respectively. The firing of both I-DEC and I-AUG neurons was increased and prolonged in association with the augmented inspiratory activity of the phrenic nerve. The activity of E-AUG neurons of the VRG did not parallel the abdominal nerve activity, suggesting the existence of additional neurons which participate in the generation of abdominal nerve activity during fictive coughing. 4. During fictive swallowing, half of I-DEC neurons fired transiently at the onset of hypoglossal bursts associated with swallowing; the firing was suppressed during the rest of the hypoglossal bursts. Other I-DEC neurons were silent during hypoglossal bursts. Some I-AUG neurons fired during the initial half of hypoglossal bursts, and others were silent. The brief phrenic activity accompanying the swallowing might have originated from this activity in I-AUG neurons. The discharges of all E-AUG neurons (BOT and VRG) and the majority of E-DEC BOT neurons were suppressed during swallowing. 5. We conclude that these five types of respiratory neurons of the BOT and VRG are involved in the generation of the spatiotemporally organized activity of coughing and swallowing, and that at least a part of the neuronal network for respiration is shared by networks for these non-respiratory activities.
Topics: Action Potentials; Animals; Cats; Cough; Decerebrate State; Deglutition; Electric Stimulation; Electrophysiology; Female; Laryngeal Nerves; Male; Neurons; Respiratory Mechanics; Respiratory System
PubMed: 7869246
DOI: 10.1113/jphysiol.1994.sp020361 -
Journal of Applied Physiology... Sep 2018Spinal cord injury (SCI) at the level of cervical segments often results in life-threatening respiratory complications and requires long-term mechanical ventilator...
Spinal cord injury (SCI) at the level of cervical segments often results in life-threatening respiratory complications and requires long-term mechanical ventilator assistance. Thus restoring diaphragm activity and regaining voluntary control of breathing are the primary clinical goals for patients with respiratory dysfunction following cervical SCI. Epidural stimulation (EDS) is a promising strategy that has been explored extensively for nonrespiratory functions and to a limited extent within the respiratory system. The goal of the present study is to assess the potential for EDS at the location of the phrenic nucleus (C-C) innervating the diaphragm: the main inspiratory muscle following complete C cervical transection. To avoid the suppressive effect of anesthesia, all experiments were performed in decerebrate, C cervical transection, unanesthetized, nonparalyzed ( n = 13) and paralyzed ( n = 7) animals. Our results show that C segment was the most responsive to EDS and required the lowest threshold of current intensity, affecting tracheal pressure and phrenic nerve responses. High-frequency (200-300 Hz) EDS applied over C segment (C-EDS) was able to maintain breathing with normal end-tidal CO level and raise blood pressure. In addition, 100-300 Hz of C-EDS showed time- and frequency-dependent changes (short-term facilitation) of evoked phrenic nerve responses that may serve as a target mechanism for pacing of phrenic motor circuits. The present work provides the first report of successful EDS at the level of phrenic nucleus in a complete SCI animal model and offers insight into the potential therapeutic application in patients with high cervical SCI. NEW & NOTEWORTHY The present work offers the first demonstration of successful life-supporting breathing paced by epidural stimulation (EDS) at the level of the phrenic nucleus, following a complete spinal cord injury in unanesthetized, decerebrate rats. Moreover, our experiments showed time- and frequency-dependent changes of evoked phrenic nerve activity during EDS that may serve as a target mechanism for pacing spinal phrenic motor networks.
Topics: Animals; Blood Pressure; Carbon Dioxide; Cervical Cord; Decerebrate State; Electric Stimulation; Epidural Space; Heart Rate; Male; Phrenic Nerve; Rats; Rats, Sprague-Dawley; Recovery of Function; Respiration; Respiratory Muscles; Spinal Cord Injuries
PubMed: 29771608
DOI: 10.1152/japplphysiol.00895.2017 -
Journal of Neurophysiology Oct 2012Anatomical and pharmacological studies have shown that the lateral superior olive (LSO) receives inputs from a number of sources and that LSO cells can alter the balance...
Anatomical and pharmacological studies have shown that the lateral superior olive (LSO) receives inputs from a number of sources and that LSO cells can alter the balance of their own excitatory and inhibitory drive. It is thus likely that the ongoing sound-evoked responses of LSO cells reflect a complex interplay of excitatory and inhibitory events, which may be affected by anesthesia. The goal of this study was to characterize the temporal discharge patterns of single units in the LSO of unanesthetized, decerebrate cats in response to long-duration ipsilateral best-frequency tone bursts. A decision tree is presented to partition LSO units on the basis of poststimulus time histogram shape, adaptation of instantaneous firing rate as a function of time, and sustained discharge rate. The results suggest that LSO discharge patterns form a continuum with four archetypes: sustained choppers that show two or more peaks of activity at stimulus onset and little adaptation of rate throughout the response, transient choppers that undergo a decrease in rate that eventually stabilizes with time, primary-like units that display an initial peak of activity followed by a monotonic decline in rate to a steady-state value, and onset-sustained units that exhibit an initial peak of activity at stimulus onset followed by a low sustained activity. Compared with the chopper units, the nonchopper units tend to show longer first-spike latencies, lower peak firing rates, and more irregular sustained discharge patterns. Modeling studies show that the full range of LSO response types can be obtained from an underlying sustained chopper by varying the strength and latency of a sound-driven ipsilateral inhibition relative to that of excitation. Together, these results suggest that inhibition plays a major role in shaping the temporal discharge patterns of units in unanesthetized preparations.
Topics: Action Potentials; Animals; Auditory Pathways; Brain Stem; Cats; Decerebrate State; Models, Neurological
PubMed: 22745462
DOI: 10.1152/jn.00908.2011 -
British Journal of Pharmacology Mar 19741 The relative potencies of methotrimeprazine, (+)-methotrimeprazine, (+/-)-10-(3-dimethylamino-2-methylpropyl)-2-valeroyl phenothiazine hydrochloride (M & B 18,706) and... (Comparative Study)
Comparative Study
1 The relative potencies of methotrimeprazine, (+)-methotrimeprazine, (+/-)-10-(3-dimethylamino-2-methylpropyl)-2-valeroyl phenothiazine hydrochloride (M & B 18,706) and (+)-M & B 18,706 in reducing the pressor action of noradrenaline in the spinal cat, reducing intercollicular decerebrate rigidity, and muscle spindle afferent activity have been studied.2 Methotrimeprazine was eight times as potent as (+)-methotrimeprazine in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity. M & B 18,706 was also eight times as potent as (+)-M & B 18,706 in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity.3 For the above compounds and chlorpromazine there was a significant correlation between the effective doses for the inhibition of the pressor action of noradrenaline and for the reduction of decerebrate rigidity.4 The doses which reduced decerebrate rigidity were similar to those that reduced muscle spindle afferent discharge. It is likely that these drugs reduce decerebrate rigidity by inhibiting fusimotor activity.5 Desipramine increased decerebrate rigidity and increased spindle afferent discharge.6 It is thought that the phenothiazine derivatives studied reduce decerebrate rigidity and spindle afferent discharge by inhibiting receptors for noradrenaline in the central nervous system.
Topics: Animals; Blood Pressure; Cats; Chlorpromazine; Decerebrate State; Desipramine; Dimethylamines; Dose-Response Relationship, Drug; Methotrimeprazine; Muscle Rigidity; Muscle Spindles; Nictitating Membrane; Norepinephrine; Phenothiazines; Receptors, Adrenergic; Serotonin Antagonists; Structure-Activity Relationship; Valerates
PubMed: 4277330
DOI: 10.1111/j.1476-5381.1974.tb09610.x -
Brain Research Jan 1997Eleven of 40 decerebrated cats were found to exhibit periods of spontaneous or sensory myoclonus and locomotion beginning 24 h after decerebration. Histological analysis...
Eleven of 40 decerebrated cats were found to exhibit periods of spontaneous or sensory myoclonus and locomotion beginning 24 h after decerebration. Histological analysis showed that the cats generating myoclonus hemorrhagic lesions in the retrorubral nucleus (RRN) and ventral mesopontine junction (vMPJ). However, with intact RRN and vMPJ never showed myoclonus. To verify that the lesions were responsible for myoclonus, 6 additional cats received N-methyl-D-aspartate (NMDA, 0.5 M/0.5 microliter) injections in the areas of RRN and vMPJ to produce bilateral lesions. Coordinated rhythmic leg movement (locomotion) or myoclonic twitches developed in all of these cats beginning 3 hours after NMDA injection. These NMDA lesion-induced movements appeared either spontaneously (5 out of 6 cats) or after sensory stimulation (1 cat). Four cats received saline control injections in the RRN and vMPJ and did not have spontaneous, or sensory stimulation-induced, myoclonic twitches during the 48 h observation period. These results indicate that the RRN and vMPJ have a suppressive effect on myoclonic twitches and rhythmic leg movement. Dysfunction of these regions could release motor activity into sleep and waking states.
Topics: Animals; Brain Stem; Cats; Cerebral Hemorrhage; Decerebrate State; Electric Stimulation; Female; Locomotion; Male; Myoclonus; Neurons; Physical Stimulation; Sleep, REM
PubMed: 9037417
DOI: 10.1016/s0006-8993(96)01177-8 -
The Journal of Physiology Aug 2010The nervous control of expiratory muscles is less well understood than that of the inspiratory muscles, particularly in the rat. The patterns of respiratory discharges...
The nervous control of expiratory muscles is less well understood than that of the inspiratory muscles, particularly in the rat. The patterns of respiratory discharges in adult rats were therefore investigated for the muscles of the caudal intercostal spaces, with hypercapnia and under either anaesthesia or decerebration. With neuromuscular blockade and artificial ventilation, efferent discharges were present for both inspiration and expiration in both external and internal intercostal nerves. This was also the case for proximal internal intercostal nerve branches that innervate only internal intercostal and subcostalis muscles. If active, this region of muscle in other species is always expiratory. Here, inspiratory bursts were almost always present. The expiratory activity appeared only gradually and intermittently, when the anaesthesia was allowed to lighten or as the pre-decerebration anaesthesia wore off. The intermittent appearance is interpreted as the coupling of a slow medullary expiratory oscillator with a faster inspiratory one. The patterns of nerve discharges, in particular the inspiratory or biphasic activation of the internal and subcostalis layers, were confirmed by observations of equivalent patterns of EMG discharges in spontaneously breathing preparations, using denervation procedures to identify which muscles generated the signals. Some motor units were recruited in both inspiratory and expiratory bursts. These patterns of activity have not previously been described and have implications both for the functional role of multiple respiratory oscillators in the adult and for the mechanical actions of the muscles of the caudal intercostal spaces, including subcostalis, which is a partly bisegmental muscle.
Topics: Anesthesia, General; Animals; Biological Clocks; Decerebrate State; Exhalation; Female; Inhalation; Motor Neurons; Muscle Contraction; Pattern Recognition, Automated; Rats; Rats, Sprague-Dawley; Respiratory Muscles
PubMed: 20530111
DOI: 10.1113/jphysiol.2010.192518 -
The Journal of Physiology Mar 19891. Mechanical actions of heterogenic (intermuscular) reflexes arising from proprioceptors in flexor and extensor ankle muscles were measured in intercollicular and...
1. Mechanical actions of heterogenic (intermuscular) reflexes arising from proprioceptors in flexor and extensor ankle muscles were measured in intercollicular and premammillary decerebrate cats. Length inputs were applied to the freed tendons of one of a pair of muscles crossing the ankle joint and resulting changes in force in both muscles were measured. Interactions between autogenic and heterogenic reflexes were studied by applying length changes to both muscles. 2. A consistent asymmetry was observed in the heterogenic inhibition between the single-joint antagonists soleus and tibialis anterior (TA). Inhibition from soleus to TA was weak or absent during the reflex activation of TA. In contrast, a strong heterogenic inhibition was consistently observed from TA to soleus during the activation of soleus by a crossed-extension reflex. The effect of this inhibition in the intact joint is to increase the apparent mechanical stiffness of soleus. 3. Mutual synergism among soleus, medial gastrocnemius (MG) and lateral gastrocnemius (LG) was demonstrated only at low to moderate forces by the observation of excitatory reflexes among them. During a naturally or electrically evoked crossed-extension reflex, however, a unidirectional inhibitory reflex from MG and LG to soleus was observed. This inhibition increased with force in MG or LG. These results suggest that the knee and ankle joints become more tightly linked mechanically at high forces since the stiffness of the biarticular gastrocnemius muscle predominates over that of the uniarticular soleus. 4. Under quiescent conditions (no resting muscle activation), mutual synergism was obeyed among the ankle extensors soleus, LG and MG and also between the pretibial flexors TA and extensor digitorum longus (EDL). Moreover, inhibition was generally observed between a pretibial flexor and an ankle extensor. Departures from this expected pattern of heterogenic reflexes occurred when the muscle groups were activated by crossed-extension and flexion reflexes. Reflexes onto soleus, TA and EDL reversed in sign or increased in magnitude. 5. The observed patterns of reflex connectivity among the ankle flexors and extensors were similar in both intercollicular and premammillary preparations, although changes in reflex strength were sometimes noted in cases where a second, lower transection was performed during the experiment. 6. It is argued from the large magnitudes of certain heterogenic reflexes that the mechanical response properties of muscles crossing the ankle joint in the intact animal are not dominated by autogenic reflexes and intrinsic mechanical properties.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Ankle Joint; Cats; Decerebrate State; Electric Stimulation; Electromyography; Female; Male; Mechanoreceptors; Muscles; Proprioception; Reflex, Stretch
PubMed: 2795487
DOI: 10.1113/jphysiol.1989.sp017544 -
American Journal of Physiology.... Jun 2012An exaggerated exercise pressor reflex (EPR) contributes to exercise intolerance and excessive sympathoexcitation in the chronic heart failure (CHF) state, which is...
An exaggerated exercise pressor reflex (EPR) contributes to exercise intolerance and excessive sympathoexcitation in the chronic heart failure (CHF) state, which is prevented by exercise training (ExT) at an early stage in the development of CHF. We hypothesized that ExT has a beneficial effect on the exaggerated EPR by improving the dysfunction of muscle afferents in CHF. We recorded the discharge of mechanically sensitive (group III) and metabolically sensitive (group IV) afferents in response to static contraction, passive stretch, and hindlimb intra-arterial injection of capsaicin in sham+sedentary (Sed), sham+ExT, CHF+Sed, and CHF+ExT rats. Compared with sham+Sed rats, CHF+Sed rats exhibited greater responses of group III afferents to contraction and stretch, whereas the responses of group IV afferents to contraction and capsaicin were blunted. ExT prevented the sensitization of group III responses to contraction or stretch and partially prevented the blunted group IV responses to contraction or capsaicin in CHF rats. Furthermore, we investigated whether purinergic 2X (P2X) and transient receptor potential vanilloid 1 (TRPV1) receptors mediate the altered sensitivity of muscle afferents by ExT in CHF. We found that the upregulated P2X and downregulated TRPV1 receptors in L4/5 dorsal root ganglia of CHF rats were normalized by ExT. Hindlimb intra-arterial infusion of a P2X antagonist attenuated the group III response to contraction or stretch in CHF rats to a greater extent than in sham rats, which was normalized by ExT. These findings suggest that ExT improves the abnormal sensitization of muscle afferents in CHF at least, in part, via restoring the dysfunction of P2X and TRPV1 receptors.
Topics: Afferent Pathways; Animals; Blotting, Western; Capsaicin; Chronic Disease; Decerebrate State; Electrophysiology; Heart Failure; Hindlimb; Immunohistochemistry; Muscle Contraction; Muscle, Skeletal; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2X; TRPC Cation Channels
PubMed: 22496362
DOI: 10.1152/ajpregu.00054.2012 -
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 -
The Journal of Neuroscience : the... Dec 2004CNS delivery of Urocortin I (UcnI), a member of the corticotropin-releasing factor family, suppresses feeding behavior and increases plasma glucose. The sites of action...
CNS delivery of Urocortin I (UcnI), a member of the corticotropin-releasing factor family, suppresses feeding behavior and increases plasma glucose. The sites of action necessary and sufficient for these responses remain unclear. The contribution of the caudal brainstem was explored using chronically maintained decerebrate (CD) and neurologically intact control rats given fourth-ventricle injections of UcnI. Ingestive and glycemic responses were evaluated, and Fos immunoreactivity was measured in the paraventricular nucleus of the hypothalamus (PVN), the parabrachical nucleus (PBN), the rostral ventrolateral medulla (RVLM), and the nucleus of the solitary tract (NTS). CD rats, like the neurologically intact controls, decreased intraoral food intake and had elevated plasma glucose in response to Unc1 injections, indicating that forebrain structures are not required for these behavioral and physiological actions of UcnI. Fos immunohistochemistry, however, revealed notable differences in the pattern of UcnI-induced activation between intact and CD rats. UcnI-related activation was observed in each of the four aforementioned brain areas of neurologically intact rats but only in the NTS of CD rats. The intact behavioral and physiological responses to UcnI in the absence of neural activation in the PVN, PBN, and RVLM help limit the list of structures necessary for the stimulation and mediation of these responses to UcnI and suggest that the NTS may serve as a primary site of UcnI action.
Topics: Animals; Blood Glucose; Brain; Brain Stem; Corticotropin-Releasing Hormone; Decerebrate State; Feeding Behavior; Homeostasis; Immunohistochemistry; Injections, Intraventricular; Male; Nerve Tissue Proteins; Neural Pathways; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Urocortins
PubMed: 15601952
DOI: 10.1523/JNEUROSCI.2702-04.2004