Intrapericardial algogenic chemicals evoke cardiac-somatic motor reflexes in rats.

Many patients suffer from secondary muscle hyperalgesia after experiencing angina pectoris. Electrophysiological studies have also demonstrated electromyography (EMG) activities evoked during brief occlusion of the coronary artery in cats. Our objectives are: (1) to develop an animal model to study muscle changes resulting from cardiac dysfunction and (2) to investigate possible links between muscle hyperalgesia and EMG activities observed with ischemic heart diseases. Intrapericardial infusion of algogenic chemicals produced EMG activities in paraspinal muscles. Among these paraspinal muscles, the spinotrapezius produced the most consistent responses (38/53 animals). The evoked responses, in most cases, persisted longer than 90 s (29/53 muscles). The EMG activities consisted of three patterns of motor-unit discharge, namely single-unit, complex, and ventilation-related. The duration of the patterns, as well as the shape and amplitude of the motor-unit waveforms, are similar to the characteristics of muscle spasms. Since sensitization of muscle afferent fibers by noxious stimuli could produce angina-like pain, the spasm-like EMG activities might sensitize muscle afferent fibers that contribute to acute angina pain and secondary muscle hyperalgesia of cardiac patients.     

Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic-ischemic injury

Severe perinatal hypoxia-ischemia is an important cause of brain injury in both full-term and premature newborns, with a high risk of future behavioral and neurological deficits. The most commonly used animal model of neonatal hypoxia-ischemia is the unilateral ligation of the common carotid artery followed by exposure to hypoxia in 7-day-old rats. In spite of the wide use of this model, lot of contradictions and discrepancies exist between the results obtained by different laboratories regarding behavioral deficits and there are no data regarding the possible delay of the appearance of neurological reflexes and the time-course of reflex performances following neonatal hypoxic-ischemic injury in rats. In the present study we showed that neonatal hypoxia-ischemia retarded the development of somatic growth and several neurological reflexes (ear twitch, grasping, gait and negative geotaxis). Hypoxic animals also displayed retarded performance in righting, geotaxis and gait reflexes. Although hypoxic pups performed worse in most tests for motor coordination, they reached normal levels by 5 weeks of age except in the footfault test. In the open-field, hypoxic animals were generally more active, except at 3 weeks, when activity of normal pups increased enormously as well. Brain areas were significantly reduced in hypoxic animals, but no close correlation was found with behavioral deficits.     

Development of neurological reflexes and motor coordination in rats neonatally treated with monosodium glutamate

Monosodium glutamate (MSG) treatment of neonatal rats causes neuronal degeneration in various brain areas and leads to several neurochemical, endocrinological and behavioral alterations. However, relatively little is known about the development of neurological reflexes and motor coordination of these animals. Therefore, the aim of the present study was to examine the neurobehavioral development of newborn rats treated with MSG. Rats received MSG at postnatal days 1, 3, 5, 7, and 9. Appearance of neural reflexes and reflex performance as well as motor coordination were examined for 5 weeks after birth. The efficacy of MSG treatment was confirmed by histological examination of the arcuate nucleus. We found that MSG treatment delayed the appearance of forelimb placing, forelimb grasp and righting reflexes, besides the retarded somatic development. The treated pups performed surface righting in significantly longer times. Also, worse performance was observed in the foot-fault and rota-rod tests. However, MSG-treated rats reached control levels by the end of the fifth postnatal week. These results show that MSG treatment does not cause permanent alterations in the neurobehavioral development, only delays the appearance of some reflexes and leads to temporary changes in reflex performance and motor coordination signs.     

Neural pathways of somatic and visceral reflexes of the external urethral sphincter in female rats

The external urethral sphincter (EUS) plays a crucial role in maintaining urinary continence. The activity of the EUS is modulated by bladder and urethra sensory neurons. However, a complete understanding of the somatic or visceral sources that modulate the EUS is lacking. The aims of the present study were to characterize the response of the EUS to perineal skin, genital, rectal, and urethral mechanical stimulation, as well as to determine the peripheral neural pathways of the reflex. EUS reflex electromyographic activity (EMG), innervation of pelvic and perineal structures, and the anatomy of afferent and efferent nerves were determined in anesthetized female rats. The EUS responds to cutaneous as well as genital and rectal stimuli. However, the EUS EMG response is significantly larger when induced by genital stimulation. The dorsal nerve of the clitoris and the cavernous nerve both innervate the distal urethra and the distal vagina, as well as the clitoris and perigenital skin and are the main afferent pathways for the genito‐sphincteric reflex. Efferent axons travel through the pudendal nerve and the lumbosacral trunk and converge in the motor branch of the lumbosacral plexus, which innervates the EUS. Because the nerves are located on the vaginal walls, they are susceptible to damage during childbirth. Physiology and anatomy of the different neural pathways that regulate EUS activity are important to consider when inducing nerve damage to create models of urinary incontinence. J. Comp. Neurol., 520:3120–3134, 2012. © 2012 Wiley Periodicals, Inc.     

Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD

The pathogenesis of Autism Spectrum Disorder (ASD), a serious neurodevelopmental disorder, is poorly understood. We review evidence for alterations in glutamatergic signalling in the aetiology of ASD, with a focus on the metabotropic glutamate receptor-5 (mGluR5). mGluR5 signalling is important for synapse formation, neuroplasticity and long term potentiation as well as neuroprotection and has been shown to have a regulatory role in neuroinflammation. Evidence for neuroinflammation in ASD is supported by increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid (CSF) and increased number and activation of microglia in postmortem dorsolateral prefrontal cortex (DLPFC). mGlur5 signalling has also been shown to downregulate microglial activation. Therefore, we focus on mGluR5 as a potential unifying explanation for synapse alteration and neuroinflammation seen in ASD. Data from mGluR5 knockout mouse models, and syndromic and non syndromic forms of ASD are discussed in relation to how alterations in mGluR5 are associated with ASD symptoms. This review supports altered mGluR5 functioning as a convergent point in ASD pathogenesis and indicates more research is warranted into mGluR5 as a potential therapeutic target.     

Spinal pathways involved in the control of forelimb motor function in rats

There is increasing interest in developing rodent models for cervical spinal cord injury (SCI) and techniques to assess forelimb motor function. Previously, we demonstrated that in rats, complete unilateral hemisection at cervical level five (C5) permanently eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion [Anderson, K.D., Gunawan, A., Steward, O., 2005. Quantitative behavioral analysis of forepaw function after cervical spinal cord injury in rats: Relationship to the corticospinal tract. Exp. Neurol. 194, 161-174]. Here, we analyzed the functional consequences of partial lesions that damaged tracts/cells located in the medial vs. lateral portion of the spinal cord. Female Sprague-Dawley rats were trained on the Grip Strength Meter (GSM) and the food pellet reaching task. Rats then received either a "medial lesion" that destroyed an approximately 0.5 mm wide zone from the midline laterally (which included the dorsal column) or "lateral lesion" that destroyed the lateral column at C5 and were tested for 8 weeks. Rats with histologically-verified medial lesions exhibited a complete loss of gripping ability for 7 weeks post-injury; only 1 of 4 animals exhibited any recovery of grip strength, and this occurred at 54 days. In contrast, rats with lateral lesions exhibited deficits, but the majority (7/10) recovered the ability to grip by 43 days post-injury. Interestingly, when tested on the food retrieval task, rats with medial lesions exhibited deficits that recovered; rats with lateral lesions exhibited more permanent deficits. These results suggest that different spinal circuits are involved in recovery of grip strength vs. recovery of skilled reaching.     

The somato-adrenal medullary reflexes in rats

In chloralose-urethane-anesthetized rats, the effects of somatic stimulation on the adrenal sympathetic efferent nerve activity as well as the adrenal catecholamine secretion were examined. Single shock of the thoracic thirteenth spinal afferent nerve evoked reflex discharges in the adrenal sympathetic efferent nerve. The spinal and supraspinal reflex components evoked by the myelinated and unmyelinated afferent stimulation were identified. The adrenal nerve activity was usually increased reflexly by pinching of the lower chest or upper abdominal skin area in the central nervous system (CNS)-intact animals. Secretion of adrenal epinephrine was noted to be increased reflexly by pinching the lower chest or upper abdominal skin in the central nervous system intact animals.     

Spinal reflexes provide motor error signals to cerebellar modules—relevance for motor coordination

The cerebellar olivo–cortico–nuclear network influencing rubro- and corticospinal tracts via the nucleus interpositus anterior (NIA) is one of the most thoroughly characterized mammalian motor systems involved in limb movement control. Recent findings indicate that climbing fibres innervating the NIA system mediate highly integrated sensorimotor information derived from spinal withdrawal reflex modules. In the present paper, the implications of this relationship between spinal and cerebellar neuronal networks for cerebellar sensorimotor processing are put in perspective of the modular organization of the NIA system. Data that should prove useful for computational models of cerebellar sensorimotor processing and motor learning, including functional spino–olivo–cortico–nucleo–spinal connectivity, are reviewed. It is argued that spinal ‘pre-processing’ of climbing fibre input constitutes a signal conversion from ‘sensory’ to ‘motor’ coordinates, providing the cerebellar modules with motor error signals relevant to the action of single limb muscles. Drawing upon their patterns of interconnectivity with spinal reflex modules it is hypothesized how cerebellar modules may adaptively coordinate transitions between agonist and antagonist muscle activity. This mechanism would contribute to the generation of the triphasic EMG patterns that are necessary for smooth acceleration and deceleration of single-joint movements.     

Demonstration of axon reflexes in human motor nerve fibres

Responses of single muscle fibres to electrical stimulation of the tibial nerve trunk or of the intramuscular nerve twigs were detected in young volunteers without evidence of neurological disease. With suitably adjusted amplitude of the stimulus, clear-cut double distribution of the response latencies was obtained in some fibres. Experiments with two stimulating cathodes and with recordings from more than one muscle fibre in the same motor unit suggest that axon reflexes were involved. The results indicate that axonal branching normally occurs not only in the intramuscular course of the nerve but also outside the muscle, in some cases even rather high in the nerve trunk. The possibility is discussed that axon reflexes may underlie fasciculations evoked by neostigmine and those seen in some other conditions, such as amyotrophic lateral sclerosis, as well as muscle cramps in normal subjects.     

Medullary pathways involved in cardiac sympathoexcitatory reflexes in the cat

Stimulation of cardiac sympathetic afferents evokes excitatory cardiovascular reflexes. However, the exact regions in the brain that integrate these reflexes have not been identified. Expression of c-Fos in the neurons provides a useful marker of the activated neurons. In the present study, we examined the response of c-Fos within the medulla of the cat to chemical stimulation of cardiac sympathetic afferents. After bilateral sinoaortic denervation and cervical vagotomy, we applied bradykinin (BK, 1-10 microg, n=7) six times to the anterior ventricular surface every 20 min. We observed consistent increases in blood pressure and heart rate while the vehicle for BK (0.9% saline, n=6) produced no responses. Ninety minutes after the end of the sixth treatment, transcardial perfusion was performed with 4% paraformaldehyde and the brainstem was harvested for immunohistochemical staining. Compared to the control animals, we noted Fos immunoreactive neurons in the nucleus of the solitary tract, lateral tegmental field, caudal and rostral ventrolateral medulla (VLM), and vestibular nucleus in the BK-treated cats (all P<0.05). Fos immunoreactivity was found in catecholaminergic neurons of the VLM. These findings indicate that the activated neurons in the medulla, especially in the VLM, are involved in integration of cardiac-cardiovascular sympathoexcitatory reflexes.     

Somatovesical and vesicovesical excitatory reflexes in urethane-anaesthetized rats

The effect of spinal cord transection on excitatory somato- and vesicovesical micturition reflexes have been investigated in urethane-anaesthetized rats. In adult rats, 3 distinct types of excitatory reflexes to the bladder may be observed: a somatovesical reflex organized at spinal level and two vesicovesical reflexes organized at spinal and supraspinal level, respectively. In agreement with results of lesion experiments (Neurosci. Lett., 8 (1978) 27-33), bladder voiding is abolished following spinal cord transection although both somato- and vesicovesical reflexes may be demonstrated in acute spinal rats. Occurrence of the spinal vesicovesical reflex during the collecting phase of the cystometrogram appears to be inhibited by a supraspinal inhibitory pathway.     

Palatal and pharyngeal reflexes in health and in motor neuron disease.

Palatal and pharyngeal sensation and motor responses, and volitional palatal movement, were tested in 171 healthy adults and 43 patients with motor neuron disease. In healthy adults palatal and pharyngeal sensation and volitional palatal elevation were present in all; the palatal and pharyngeal motor responses could not be elicited on first testing in two (1.1%) and seven (4.1%) subjects respectively. Pharyngeal motor responses were more easily elicited in older subjects and palatal responses were more easily elicited in women. Eye watering and retching were the most common accompanying features. In 57 normal subjects tested on five occasions there was considerable variation in the stimulus required to elicit the motor responses within subjects: in none of four subjects (7%) who initially had absent responses were they always absent. Pharyngeal motor responses were more easily elicited in patients with motor neuron disease than in matched normal subjects; within the motor neuron disease group pharyngeal motor responses elicited by tongue depression were associated with the symptom of food or drink "going down the wrong way" > 1/month and a reduction in average volume per swallow (ml) and swallowing capacity (ml/s). Volitional palatal elevation was absent in five patients (11.6%). In six of eight patients with motor neuron disease studied repeatedly (on between two and seven occasions) the palatal and pharyngeal responses were elicited with the same stimulus on each occasion. In healthy adults palatal and pharyngeal sensation and motor responses should be present although considerable variation occurs in the stimulus required. In patients with motor neuron disease features of impaired swallowing are associated with a brisk rather than a depressed pharyngeal response.     

Blind evaluation of body reflexes and motor skills in learning disability

Motor dysfunctions have been associated with learning disabilities in casual observation and systematic study. However, most prior work has concentrated solely on high-level skills and has been subject to observer bias. In this study, boys with learning disability were blindly compared with paired controls on measures of postural and equilibrium reflexes as well as skills. Learning-disabled children as a group showed significant deficits on all measures; a few, however, were totally without deficit. The implications of these findings for controversies about the role of motor dysfunction in learning disabilities are examined. Funds for the purchase of videotapes were donated to Emory University in support of the research efforts of the senior author by relatives and friends in memory of the late Paul E. Connelly of Tampa, Florida, We are grateful to Elinore O. McCandless, of the Dekalb County (Georgia) Program for Children with Specific Learning Disabilities, and to Mr. William Simpson, who was principal of the Wadsworth School in DeKalb County at the time of the study, for assistance in arranging and conducting the research.