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[Ascending and descending efferent pathways of the midbrain reticular formation of the cat (radioautographic study)].

By means of the anterograde axoplasmic transport technique for a mixture of labelled aminoacids (3H-leucine and 3H-proline), ascending and descending systems of the reticular formation fibers in the cat mesencephalon have been studied. Projections from the mesencephalon reticular formation (MRF) ascend to the subthalamus, lateral, dorsal and periventricular hypothalamus, to the periventricular nuclei of the midline and to the intralaminar nuclei of the thalamus. The descending pathways project to the grey substance surrounding the aqueduct of cerebrum, locus coeruleus, parabrachial region and reticular formation of the pons and medulla oblongata. The projections to the reticular nucleus of the thalamus, ventral nucleus of the external geniculate body and superior colliculi arise from the dorsal half of the MRF, and projections to the striatum, lateral reticular nucleus of the medulla oblongata--from its ventral half. Most of the structures are reciprocally connected with the MRF.

Animals↗

[Evaluation of the vagal efferent pathway in rats in the acute and chronic phases of myocardial infarction].

PURPOSE: To investigate the sensitivity of the muscarinic receptors to acetylcholine (Ach) and to vagal stimulation in rats during the acute and the chronic phases of myocardial infarction (MI). METHODS: Male albino rats were submitted to ligature of the descending anterior branches of the left coronary artery to produce MI. Control rats (Con) were submitted to a sham surgery. The animals were studied 1-3 days (acute phase) or 30 days (chronic phase) after surgery. Under anesthesia (ketamine+xylazine) the right vagus nerve was isolated at the neck and stimulated with suprathreshold pulses (2ms, 1-64Hz). Atrial and ventricular rates were measured in the ECG recording. Dose-response curve to Ach (5-80 micrograms) was studied in the isolated hearts perfused according to the Langendorftechnique. Atrial and ventricular rates were evaluated through the surface electrogram recording. The left ventricular pressure was measured with an intraventricular balloon. RESULTS: Basal heart rate in the anesthetized animals was similar in Con and MI rats. The vagal stimulation produced a frequency dependent reduction of the heart rate. This reduction was less intense in the MI groups to stimulation rates of 32 and 64Hz. It was not observed any difference in the sensitivity of sinus and AV nodes to exogenous Ach in infarcted hearts. The reduction of the systolic pressure obtained after Ach administration to the hearts paced artificially (3.3Hz) was similar in MI and Con hearts. CONCLUSION: MI hearts were less sensitive to vagal stimulation than Con hearts. Since the in vitro effects of Ach remained unchanged after infarction, these results suggest an impairment of the cardiac neuroeffector vagal synapse. This may contribute to a less efficient control of the heart rate by the parasympathetic pathway in infarcted individuals.

Acetylcholine↗

[Orthostatic hypotension and postprandial hypotension].

Both orthostatic hypotension (OH) and postprandial hypotension (PPH) may result from lesions in any part of the baroreflex arc, which comprises central autonomic network, afferent pathways, efferent pathways, and neuro-vascular junction. Nonetheless, most attention has been centered to the efferent pathways to date. In the present report, I discussed on the contribution of neuro-vascular junction and central autonomic network to the development of OH and PPH. I also referred to the essential difference in pathophysiology between OH and PPH. (1) Difference between OH and PPH: Essential difference is in triggers inducing the initial blood pressure fall. The trigger in OH is gravity, while that in PPH is abnormal release of vasodilative gastroenteric peptides; the former is equally delivered to all persons living on earth, but the latter varies from person to person. (2) Neuro-vascular junction: Previous studies, in which catecholamine drip infusion tests were carried out on patients with OH, suggested that all of cardiovascular alpha-, beta 1, and beta 2 adrenoceptors gain denervation supersensitivity in OH. This view does, however, underestimate the blood pressure buffering effect of baroreflex. Because long-standing alteration in blood pressure by drip infusion of catecholamine necessarily provokes baroreflex, it is reasonable that augmented cardiovascular responses in OH are largely due to baroreflex failure. We performed bolus infusion tests of noradrenaline and isoprenaline on patients with OH, and found that alpha-adrenoceptor-mediated rise in blood pressure was comparable to control, beta 1-mediated increase in heart rate was blunted, and beta 2-mediated fall in blood pressure was enhanced in OH. It is, therefore, likely that beta 2-mediated vasodilation exceeds alpha-mediated vasoconstriction in OH. In such condition, noradrenaline may produce a paradoxical hypotensive effect, which contributes to the development of OH or PPH. (3) Central autonomic network (CAN): Clinical symptoms due to lesions within CAN are usually not manifested when the efferent sympathetic pathways are highly impaired, as in multiple system atrophy. Some variants of OH and PPH may result from lesions within CAN, however. For example, we have experienced a case of sympathotonic OH associated with herpes simplex encephalitis, in which the efferent pathways do not seem to be involved.

Eating↗

Reconstruction of afferent and efferent nervous pathways to the urinary bladder in two paraplegic patients.

Based on animal experiments, spinal root anastomoses were performed in two paraplegic patients who had traumatic lesions of the conus medullaris. The aim was to reinnervate the paralyzed urinary bladder. At operation, the functioning T12 nerve roots above the lesion were transected and anastomosed bilaterally to the S2 and S3 ventral and dorsal roots emerging from the injured cord area. About 1 year postoperatively, both patients demonstrated restoration of the micturition reflex as recorded in the cystometrogram. Both patients could feel the urge to void, could initate micturition voluntarily, and could empty their bladders satisfactorily. The patients' relatively good bladder functions were the result of either regeneration of the newly constructed nervous pathways or spontaneously developed reflex bladders in partial upper neuron lesions.

Adult↗

Vocal pathways modulate efferent neurons to the inner ear and lateral line.

All sonic vertebrates face the problem of sound production interfering with their ability to detect and process external acoustic signals, including conspecific vocalizations. Direct efferent inputs to the inner ear of all vertebrates, and the lateral line system of some aquatic vertebrates, represent a potential mechanism to adjust peripheral sensitivity during sound production. We recorded from single efferent neurons that innervate the inner ear and lateral line in a sound-producing teleost fish while evoking fictive vocalizations predictive of the temporal features of natural vocalizations. The majority of efferent neurons showed an increase in activity that occurred in-phase with modulations in the fine temporal structure of the fictive vocalizations. Many of these neurons also showed a decrease in activity at fictive vocal offset. Efferents to the sacculus, the main auditory end organ, showed features especially well adapted for maintaining sensitivity to external acoustic signals during sound production. These included robust phase locking of efferent activity to each cycle of a fictive vocalization and a long-duration rebound suppression after each fictive vocalization that could provide a rapid, long-lasting period of sensitization to external acoustic stimuli such as the call of a conspecific. These results suggest that efferent activation by the vocal motor system can directly modulate auditory sensitivity to self-generated sounds and maintain sensitivity to ongoing external sounds. Given the conserved organization of the auditory efferent system across vertebrates, such mechanisms may be operative among all sonic vertebrates.

Animals↗

Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats.

OBJECTIVE: A vagus nerve-mediated, brain cholinergic protective mechanism activated by melanocortin peptides is operative in conditions of circulatory shock; moreover, there is anatomical evidence of dual vagal-cardiac efferent pathways in rats, which could play different roles in controlling heart function. Therefore, we investigated the role and functional mechanism of such vagal efferent pathway(s) in an experimental model of ischemic heart disease. DESIGN: Randomized experimental study. SETTING: Research laboratory. SUBJECTS: Adult Wistar rats of either sex. INTERVENTIONS: After bilateral cervical vagotomy (with or without pretreatment with atropine), efferent vagal fibers were electrically stimulated in rats subjected to coronary artery occlusion (5 mins) followed by reperfusion (5 mins). Other rats (intact, vagotomized, or pretreated with atropine) were treated with nanomolar doses of melanocortin peptides. MEASUREMENTS AND MAIN RESULTS: Electrical stimulation of efferent vagal fibers (5 V, 2 m secs, 1-9 Hz, for the whole period of ischemia/reperfusion) strongly reduced the high incidence of severe arrhythmias and lethality, reduced the increase in free radical blood levels and left-ventricle histologic alterations, and augmented the extracellular signal-regulated kinase activation. Treatment with the melanocortin peptides adrenocorticotropin and gamma2-melanocyte-stimulating hormone (162 nmol/kg intravenously or 16.2 nmol/kg intracerebroventricularly, during coronary occlusion) produced the same protective effects of electrical stimulation and with the same muscarinic acetylcholine receptor-dependent mechanism, seemingly through brain activation (mediated by melanocortin MC3 receptors, as previously described) of such efferent vagal pathway. CONCLUSIONS: The present results give evidence for the identification of a protective, melanocortin-activated, efferent vagal cholinergic pathway, operative in conditions of myocardial ischemia/reperfusion. These data suggest that melanocortins and pertinent compounds able to activate such a pathway could provide the potential for development of a new class of drugs for a novel approach to management of ischemic heart disease.

Animals↗

Larval development of tectal efferents and afferents in Xenopus laevis (Amphibia Anura).

The development of tectal connections in Xenopus laevis had been investigated using the degeneration technique to demonstrate the efferent pathways and the retrograde HRP transport to label the afferent pathways. Bilateral tectal efferents were present as soon as the beginning of metamorphosis. Ascending efferents originated from the anterior tectal part terminate in the secondary visual thalamic centres whereas the descending efferents coming from the posterior tectal part reached the tegmentum and the medulla oblongata. At this same time, the optic tectum already received secondary visual afferents originating in the ipsilateral pretectum and non-visual afferents from the ipsilateral semicircular torus and tegmentum. Some sparse bilateral isthmotectal connections were also present. Later, efferent pathways showed an increasing number of fibres whereas the sites of origin of afferents became more diversified: the dorsal thalamus, the suprachiasmatic area, the tegmental nuclei and in the medulla oblongata, the reticular and octavolateral areas sent bilateral projections to the optic tectum. At the end of metamorphosis, we noted ipsilateral olivotectal fibres and reciprocal connections between the tectum and the area of the Vth nerve. These last findings and the presence of the following direct projections, not previously reported in Anurans: the reciprocal connections between the tectum and the semicircular torus or the octavolateral area, underline the implication of the optic tectum in the multisensory (visual, acoustic, vibratory) integration elicited during the larval behavior. Also, the relations between the optic tectum and the lateral line system are particularly examined in the discussion.

Afferent Pathways↗

Diffuse pathways convey efferent activity from rostral pontile pneumotaxic center to medullary respiratory regions.

Studies were undertaken to evaluate the hypothesis that diffuse pathways serve to convey efferent activity from the rostral pontile pneumotaxic center to the respiratory regions of medulla. Activation of respiratory mechanisms within the pneumotaxic center was produced by electrical stimulation. In decerebrate, vagotomized, cerebellectomized, paralyzed and ventilated cats, stimulations of the pneumotaxic center produced a premature termination of activities of both phrenic nerves. Such a termination of neural activities was still obtained following hemisection of the brain stem at the pontomedullary junction either ipsilateral or contralateral to the site of stimulation. Likewise, both phrenic activities were terminated by stimulation of the pneumotaxic center after a midsagittal division of the brain stem from the intercollicular level to the medullary obex. These results demonstrate that efferent pathways from the pneumotaxic center must decussate in both the caudal pons and in the medulla. The finding of diffuse pathways from the pneumotaxic center to the medullary respiratory regions has implications for previous studies which reported a variety of respiratory patterns following a brain stem transection at the pontomedullary junction.

Animals↗

Efferent projections of the superior olivary nucleus in the frog, Rana catesbeiana.

Following electrolytic lesions of the superior olivary nucleus (SO) of the bullfrog, Rana catesbeiana, the efferent pathways of this nucleus were studied with silver impregnation methods. The major projection was to the ipsilateral principal nucleus of the torus semicircularis. Less conspicuous degeneration was traced to the nuclei magnocellularis and commissuralis of the torus. No contribution was made to the tectum or nucleus isthmi. Other projections of the SO include a sma-ler contralateral projection to these same nuclei and to the ipsilateral nucleus lateralis profundus mesencephali. A system of connections between the acoustic nuclei was invariably interrupted with these lesions and the degeneration seen in the more dorsal acoustic areas was not entirely due to the destruction of SO neurons.

Animals↗

Chondroitin sulfate proteoglycans in the developing cerebral cortex: the distribution of neurocan distinguishes forming afferent and efferent axonal pathways.

The first thalamocortical axons to arrive in the developing cerebral cortex traverse a pathway that is separate from the adjacent intracortical pathway for early efferents, suggesting that different molecular signals guide their growth. We previously demonstrated that the intracortical pathway for thalamic axons is centered on the subplate (Bicknese et al. [1994] J. Neurosci. 14:3500-3510), which is rich in chondroitin sulfate proteoglycans (CSPGs; Sheppard et al. [1991] J. Neurosci. 11:3928-3942), whereas efferent axons cross the subplate to exit in a zone containing much less CSPG. To define the molecular composition of the subplate further, we used antibodies against CSPG core proteins and chondroitin sulfate disaccharides in an immunohistochemical analysis of their distribution in the developing neocortex of the rat. Immunolabeling for neurocan, a central nervous system-specific CSPG (Rauch et al. [1992] J. Biol. Chem. 267:19537-19547), and for chondroitin 6-sulfate and unsulfated chondroitin becomes prominent in the subplate before the arrival of thalamic afferents. Immunolabeling is initially sparse in the cortical plate but appears later in maturing cortical layers. A postnatal decline in immunolabeling occurs uniformly for most proteoglycans, but, in the somatosensory cortex, labeling for neurocan, phosphacan, and chondroitin 4- and 6-sulfate declines in the centers of the whisker barrels before the walls. In contrast to neurocan, immunolabeling for other proteoglycans is either uniformly distributed (syndecan-1, N-syndecan, 5F3, phosphacan, chondroitin 4-sulfate), restricted to axons (PGM1), distributed exclusively on nonneuronal elements (2D6, NG2, and CD44), or undetectable (9.2.27, aggrecan, decorin). Thus, neurocan is a candidate molecule for delineating the intracortical pathway of thalamocortical axons and distinguishing it from that of cortical efferents.

Afferent Pathways↗

Magnetic stimulation of sacral roots for assessing the efferent neuronal pathways of lower urinary tract.

The value of sacral magnetic stimulation (SMS) in neurophysiological evaluation of the sacral efferent pathways of the lower urinary tract was assessed during urodynamic examination in 10 men with chronic suprasacral spinal cord injury (SCI) and in 7 healthy volunteers. Investigated parameters included latency and amplitude of the urodynamic pressure response of the external urethral sphincter and detrusor to different stimulation strengths (50-100%) and single or repetitive (20 and 30 Hz) stimuli. Following SMS, reproducible external urethral sphincter pressure responses (mean latency, 13 ms) were recorded in all subjects. In contrast, a detrusor pressure increase was recorded only in SCI patients after repetitive SMS, with a latency of 1-2 s. This implies the appearance of a polysynaptic spinal reflex due to changes in organization of the sacral micturition reflex after SCI. The method of SMS may be helpful for the evaluation of cases in which urodynamic studies remain inconclusive.

Adult↗

Contributions of the vestibular nucleus and vestibulospinal tract to the startle reflex.

The startle reflex is elicited by strong and sudden acoustic, vestibular or trigeminal stimuli. The caudal pontine reticular nucleus, which mediates acoustic startle via the reticulospinal tract, receives further anatomical connections from vestibular and trigeminal nuclei, and can be activated by vestibular and tactile stimuli, suggesting that this pontine reticular structure could mediate vestibular and trigeminal startle. The vestibular nucleus, however, also projects to the spinal cord directly via the vestibulospinal tracts, and therefore may mediate vestibular startle via additional faster routes without a synaptic relay in the hindbrain. In the present study, the timing properties of the vestibular efferent pathways mediating startle-like responses were examined in rats using electrical stimulation techniques. Transient single- or twin-pulse electrical stimulation of the vestibular nucleus evoked bilateral, startle-like responses with short refractory periods. In chloral hydrate-anesthetized rats, hindlimb electromyogram latencies recorded from the anterior biceps femoris muscle were shorter than those for stimulation of the trigeminal nucleus, and similar to those for stimulation of the caudal pontine reticular nucleus or ventromedial medulla. In awake rats, combining vestibular nucleus stimulation with either acoustic stimulation or trigeminal nucleus stimulation enhanced the whole-body startle-like responses and led to strong cross-modal summation without collision effects. In both chloral hydrate-anesthetized and awake rats, combining vestibular nucleus stimulation with ventromedial medulla stimulation produced a symmetrical collision effect, i.e. a loss of summation at the same positive and negative stimulus intervals, indicating a continuous connection between the vestibular nucleus and ventromedial medulla in mediating vestibular startle. By contrast, combining trigeminal nucleus stimulation with ventromedial medulla stimulation resulted in an asymmetric collision effect when the trigeminal nucleus stimulation preceded ventromedial medulla stimulation by 0.5 ms, suggesting that a monosynaptic connection between the trigeminal nucleus and ventromedial medulla mediates trigeminal startle. We propose that the vestibulospinal tracts participate strongly in mediating startle produced by activation of the vestibular nucleus. The convergence of the vestibulospinal tracts with the reticulospinal tract within the spinal cord therefore provides the neural basis of cross-modal summation of startling stimuli.

Acoustic Stimulation↗

Sex-specific patterns of galanin, cholecystokinin, and substance P expression in neurons of the principal bed nucleus of the stria terminalis are differentially reflected within three efferent preoptic pathways in the juvenile rat.

Neurons in the principal bed nucleus of the stria terminalis (BSTp) integrate hormonal and sensory information associated with reproduction and transmit this information to hypothalamic nuclei that regulate neuroendocrine and behavioral functions. The neuropeptides galanin (GAL), cholecystokinin (CCK), and substance P (SP) are highly expressed in BSTp neurons and are differentially regulated by sex steroids. The current experiments investigated whether developmental or peripubertal hormone-mediated changes in GAL, CCK, and SP expression are reflected within efferent pathways to the preoptic structures that regulate gonadotropin secretion and sexual behavior. Anterograde labeling of projections from the BSTp of male and female juvenile rats combined with immunohistochemical labeling of GAL-, CCK-, and SP-containing fibers in the anteroventral periventricular preoptic nucleus (AVPV) and the central and medial divisions of the medial preoptic nucleus (MPNc, MPNm, respectively) revealed unique sex differences in each region. In the AVPV, Phaseolus vulgaris leucoagglutinin-labeled fibers were seen at a greater density in males than in females, and higher percentages of these fibers contained GAL in males than in females. In contrast, fibers projecting from the BSTp to the MPNc were more likely to contain SP in females than in males. Treatment of gonadectomized, peripubertal males and females with exogenous testosterone and estradiol did not alter the densities of GAL-, CCK-, or SP-containing fibers in any of the three brain areas examined. Collectively, these results suggest that patterns of neuropeptide expression in BSTp projections are established during development, resulting in a distinct, stable, and sex-specific chemoarchitectural profile for each projection pathway.

Aging↗