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PubMed1984

Localization and organization of geniculocortical and corticofugal fiber tracts within the subcortical white matter.

Reciprocal connections are formed between the dorsal lateral geniculate nucleus and the striate cortex in the mammalian visual system. The question of whether fibers of these corticopetal and corticofugal pathways are segregated or intermingled within the white matter is still open. In order to examine the organization of these fiber tracts within the white matter, we have used orthograde axonal transport of radiolabelled proteins and neuronal degeneration following kainic acid lesions in the geniculocortical and corticofugal pathways of the rat. Within the white matter the two pathways reside in different layers and are segregated from one another over a significant portion of their course, geniculocortical fibers lying in the external sagittal stratum and corticofugal fibers lying in the internal sagittal stratum of the white matter. In addition, the corticofugal pathways projecting to subcortical structures appear fasciculated in both the transport and the degeneration studies suggesting that axons of cortical output neurons are organized into fiber bundles. The separation of fibers within the white matter may be of potential use for selectively stimulating afferent and efferent pathways in electrophysiological studies in situ and in cortical slice preparations. In addition, the corticofugal fiber bundles may play an important role in guiding axons therein to appropriate targets during axonogeneis and may carry the output of columnar units within visual cortex.

Animals↗
PubMed1995

Role of the time factor in signaling specificity: application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-I receptor tyrosine kinases.

The signal transduction pathways activated by hormones, growth factors, and cytokines show an extraordinary degree of cross-talk and redundancy. This review addresses the question of how the specificity conferred at the binding step is maintained through the signaling network despite the convergence of multiple signals on common efferent pathways such as mitogen-activated protein (MAP) kinase. The mechanism of receptor activation by ligand-induced dimerization provides a signaling device with both a switch and a timer. The role of the time factor, ie, of signaling kinetics, as a determinant of selectivity is discussed with emphasis on the receptor tyrosine kinases and cytokine receptors, and especially mitogenic versus metabolic signaling by insulin and insulin-like growth factor-I (IGF-I).

Animals↗
PubMed1983

Ventral medullary relay neurones in the pathway from the defence areas of the cat and their effect on blood pressure.

In cats anaesthetized with Althesin, the efferent descending pathway from the brain-stem defence areas has been traced through the medulla by identifying sites at which electrical stimulation evoked the characteristic pattern of the visceral alerting (defence) response. This response includes an increase in arterial blood pressure resulting from increased heart rate and cardiac output and vasoconstriction in renal and splanchnic beds, accompanied by active vasodilation in skeletal muscle. The efferent pathway runs as a narrow strip, about 3 mm from the mid line, ventral to the superior olive and the nucleus of the trapezoid body, extending caudally to the rostral portion of the inferior olive where it lies ventral to the facial nucleus. It was found to lie very close to the ventral medullary surface just rostral to and within the area at which bilateral topical application of glycine results in a profound fall in arterial blood pressure and cessation of respiration. On bilateral application of glycine to the sensitive area of the ventral medulla, the visceral alerting response evoked by stimulation in the defence areas of the amygdalo-hypothalamic complex, or the mid-brain central grey or tegmentum, was attenuated in parallel with the fall in arterial pressure, the vasoconstrictor responses being most strongly reduced. As soon as arterial blood pressure had fallen to its lowest level the visceral alerting response was virtually abolished. A small radio-frequency lesion made in the ventral medullary efferent pathway, in the rostral part of the 'glycine-sensitive area', had the same effect as that produced by unilateral application of glycine: it resulted in little respiratory or cardiovascular effect itself, but application of glycine to the contralateral area then produced the full effect otherwise seen only on bilateral application of glycine. It is suggested (1) that the effects of glycine result from blockade of a synaptic relay, close to the ventral surface of the medulla, in the efferent pathway from the defence areas to the preganglionic sympathetic neurones, and (2) that the neurones which receive an input from the alerting (defence) areas normally provide an essential, tonic excitatory drive to the sympathetic output and probably to respiration also. After sudden withdrawal of this drive, vasomotor tone and the normal level of arterial blood pressure are not maintained.

Animals↗
PubMed1977

The seventh cranial nerve of the rat. Visualization of efferent and afferent pathways by cobalt precipitation.

The cobalt sulphide precipitation technique, in conjunction with Timm's intensification procedure, was used to delineate the afferent and efferent intramedullary pathways of the seventh cranial nerve complex in the rat. The branchial motor nucleus with the accompanying first part, genu, and second part of the root are described. The motor branches to the superficial facial musculature do not contain fibres of geniculate ganglion origin or fibres which terminate in the spinal trigeminal nucleus. The motor branches to the deep facial muscles arise from the dorsal part of the branchial motor nucleus and traverse to the midline medial to the genu, then project under the genu into the lateral reticular formation before exiting with the facial nerve. The salivatory and lacrimal nuclei and their intramedullary pathways are described. Sensory fibres from the cutaneous auricular branch enter the spinal trigeminal tract and most of the chorda tympani gustatory fibres enter the fasciculus solitarius. A smaller number of gustatory fibres extend medially to the region of the salivatory nucleus. Fibres of greater superficial petrosal origin also enter the fasciculus solitarius as well as the medial reticular formation. These findings are discussed in relation to previous anatomical, physiological and clinical reports.

Animals↗
PubMedDate not supplied

Is demyelination a feature of maple syrup urine disease?

To determine whether disturbance of myelination is a pathophysiologic feature in patients with treated maple syrup urine disease (MSUD), neurophysiologic studies were performed in 10 MSUD patients ages 4-16 years. Afferent and efferent pathways were studied by visual evoked potentials, somatosensory evoked potentials, motor evoked potentials, stance-stabilizing reflexes, and peripheral nerve conduction velocity. Magnetic resonance imaging was used to detect possible cerebral white matter abnormalities. Visual evoked potentials were normal in all patients. There was only slight prolongation of central afferent and efferent conduction times and the long latency component of the stance-stabilizing reflexes. Peripheral nerve conduction studies revealed reduced sensory nerve conduction velocity in 3 patients. The neurophysiologic findings were not consistently correlated to the neurologic outcome of the patients. Magnetic resonance imaging did not reveal major abnormalities and demonstrated bilateral periventricular high intensity periventricular signals on T2-weighted images in 4 of 10 patients. It is concluded that dysmyelination is not a major pathophysiologic feature in patients with MSUD.

Adolescent↗
PubMed1996

Nociceptive neurones in rat superior colliculus. I. Antidromic activation from the contralateral predorsal bundle.

Accumulating evidence suggests that the rodent superior colliculus (SC) plays as important a role in avoidance and defensive behaviours as it does in orientation and approach. These two complementary behaviours are associated with two anatomically segregated tectofugal output pathways, such that orientation and approach are mediated by the crossed descending projection, whereas avoidance and defence are subserved via the uncrossed projection. Because nociceptive neurones in the SC have been presumed to participate in withdrawal or defensive behaviours, it has been proposed that they have direct access only to the uncrossed efferent pathway. However, in certain behavioural situations, the most adaptive response to injury, or to a painful object in prolonged contact with the skin, is to orient towards the source of discomfort so that the skin can be licked and/or the offending object removed. Presumably then, nociceptive as well as low-threshold neurones would have access to the crossed descending pathway in order to initiate such behaviours. Determining whether or not this is the case was the objective of the present study. Both nociceptive-specific (82%) and wide-dynamic-range (18%) SC neurones were identified using long-duration (up to 6 s), frankly noxious mechanical and thermal stimuli in urethane-anaesthetised Long-Evans hooded rats. The majority (85.7%) of the nociceptive neurones encountered were located within the intermediate layers, which corresponds with the location of the cells-of-origin of the crossed descending projection. Nearly half (44.9%) were activated antidromically from electrical stimulation of the crossed descending pathway at a site in the brainstem below its decussation. The mean conduction velocity of these nociceptive output neurones was 9.02 m/s, which corresponds well to previous estimates of conduction velocity in the crossed tecto-reticulo-spinal tract. These data demonstrate that a significant proportion of nociceptive neurones in the rat SC have axons that project to the contralateral brainstem via the crossed descending projection. Nociceptive neurones could, therefore, effect orientation responses to noxious stimuli via similar output pathways that low-threshold neurones utilize to initiate orientation to innocuous stimuli.

Animals↗
PubMed1993

Localization of NADPH diaphorase in bladder afferent and postganglionic efferent neurons of the rat.

NADPH diaphorase histochemistry was used in combination with axonal labelling techniques to determine if NADPH diaphorase is present in afferent and postganglionic efferent pathways to the urinary bladder of the rat. In the L6 and S1 dorsal root ganglia, 80.9 and 78.5%, respectively, of bladder afferent neurons labelled with fluorescent dyes were NADPH diaphorase positive. In the major pelvic ganglion (MPG), many non-labelled neurons and fibers were intensely stained for NADPH diaphorase. Intensely stained cells were clustered near the exit of the penile nerve although stained cells were also scattered throughout the ganglion. Only a small percentage (3.5%) of bladder postganglionic neurons in the MPG were NADPH diaphorase positive. Since NADPH diaphorase activity commonly reflects the presence of nitric oxide synthase, the present findings raise the possibility that nitric oxide may have a role as a neurotransmitter or neuromodulator in afferent pathways from the urinary bladder.

Amino Acid Oxidoreductases↗
PubMed1995

[Subcortical pathways related to optokinetic nystagmus in the cat].

In recent experiments, it has been disclosed that the nucleus of the optic tract (NOT) is the visut-motor relay between the retina and preoculomotor structures in the pathway mediating optokinetic nystagmus (OKN). In the present study, how OKN signals are transmitted from the NOT in the brainstem was investigated using biocytin and triticum vulgaris (Wheat Germ) peroxidase labeled (WGA-HRP) as anterograde and retrograde tracers, respectively. Following biocytin injections into the NOT, labeled fibers were observed in each of the following efferent pathways: 1) those that project to the contralateral NOT via the posterior commissure; 2) those that course through the nucleus pontis orklis to terminate in the Edinger-Westphal complex and nucleus reticularis tegmenti pontis; and 3) those that descend via the medical lemniscus to the level of the medulla to terminate in the dorsal cap of the inferior olive, during which their axons branch to the dorsolateral pontine nucleus, nucleus prepositus hypoglossi, and the nucleus pontis caudalis, superior and lateral. Furthermore, differences in the distribution of labeled cells in the NOT were observed following WGA-HRP injections into the nucleus prepositus hypoglossi and medial vestibular nucleus. The retrograde labeled cells in the NOT were distributed to the medial area at the rostral level following the tracer injections into the medial vestibular nucleus. On the other hand, labeled cells were recognized in the part of the caudal NOT following the tracer injections into the nucleus prepositus hypoglossi. A recent neurophysiological study demonstrated that areas adjacent to the medial vestibular nucleus apparently to participate in the production of OKN, because both the slow component and after-nystagmus similar to OKN and optokinetic after nystagmus were elicited by stimulation of the vestibular nuclei. The present study shows that this direct projection from the NOT to the vestibular nuclei may serve to drive velocity storage in the vestibular nuclei.

Animals↗
PubMed1984

Immunohistochemical localization of unique enkephalin sequences contained in preproenkephalin A in the guinea pig cochlea.

The guinea pig cochlea was studied for the presence of immunoreactivities to the four unique enkephalin sequences contained in the preproenkephalin A. The antisera to Met-enkephalin-Arg6-Phe7 and Met-enkephalin-Arg6-Gly7-Leu8 were used as highly specific markers for the preproenkephalin A. Contrary to Met-enkephalin and Leu-enkephalin, also included in the present study, these two peptide sequences are not contained in pro-opiomelanocortin or preproenkephalin B (prodynorphin). All the four different antisera showed identical localization for the four peptide sequences, suggesting their coexistence in the same nervous pathway. Specific immunofluorescence was found in intraganglionic spiral bundle, inner spiral bundle, tunnel spiral bundle and in association with inner hair cells. The nerve fibers were thin and varicose, suggesting that most, if not all, of them were unmyelinated. Their localization indicates that the unique enkephalin sequences contained in preproenkephalin A are present in the cochlear efferent pathway to the inner hair cell region.

Animals↗
PubMedDate not supplied

Location of the area postrema pressor pathway in the dog brain stem.

Electrical stimulation of the dog's area postrema (AP) induces a response that mimics the pressor response produced by intravertebral infusion of low-dose angiotensin II, which causes an increase in mean arterial pressure associated with transient tachycardia and increased peripheral resistance. The present study investigated in morphine-chloralose anesthetized dogs whether: 1) the characteristics of the AP pressor response are influenced by the presence of carotid sinus afferents; 2) structures rostral to the medulla influence the AP pressor response; and 3) the pressor pathway is initiated by neurons within the AP. Since bilateral cervical sinovagal denervation, which potentiated the phenylephrine pressor response, did not affect the pressor response to AP stimulation, the data provide evidence for an inhibitory influence exerted upon the central baroreflex mechanism by the AP pressor mechanism. The unaltered AP pressor response after midcollicular transection suggests that the efferent pathway is contained within the brain stem caudal to the pons. Finally, the elimination of the pressor response following kainic acid microinjection into the AP provides evidence that the AP pressor mechanism is initiated by neurons within the AP, rather than by fibers of passage from other pressor centers. These results suggest that the AP produces its facilitation of central sympathetic vasomotor outflow via a pathway contained within the medulla.

Animals↗
PubMed1994

Vaccination for treatment of tumors: a critical comment.

Tumors are resistant to the immune response as evidenced by both their progressive growth in patients despite specific humoral and cellular immune responses to tumor antigens and by the moderate clinical effect of active specific immunotherapy with tumor vaccines tested to date. This "immune resistance" may be due to various reasons, among which the most important ones are: (1) in the afferent pathway of the immune response, (a) expression of major histocompatibility complex (MHC)-class II molecules without coexpression of costimulatory B7 molecules on tumor cells, which impairs activation of T- and B-cells and, (b) release of prostaglandins and other factors from tumor cells, that may inhibit proliferation and function of helper T-cells; and (2) in the efferent pathway; (c) release of tumor antigens, which blocks cytotoxic cells and antibodies and release of proteolytic enzymes, which degrades specific antibodies; (d) reduced expression of MHC-class I molecules by tumor cells, which inhibits their recognition by cytotoxic T-lymphocytes (CTL); and (e) cell membrane-associated inhibitors of complement factors that block complement-mediated lysis. Altogether, the chance for a successful tumor therapy by tumor vaccines has to be estimated to be low. Alternatives would be to use tumor antigens as tumor cell targets for cytotoxic compounds with differing action from the cytotoxic mechanisms used by the immune system. The problems of low tumor localization rates of tumor-specific monoclonal antibodies, immune resistance of the tumor cells, and general toxicity of cytotoxic drugs may be solved by a biphasic therapeutic approach called immune specific enzyme-mediated chemotherapy. It uses, in a first phase, an appropriate antibody-enzyme fusion protein and, in the second phase, a nontoxic prodrug that is cleaved at the tumor site by the enzyme of the fusion protein into the cytotoxic drug.

Antibodies, Neoplasm↗
PubMed2001

Visual discrimination learning impairments produced by combined transections of the anterior temporal stem, amygdala and fornix in marmoset monkeys.

Marmoset monkeys (Callithrix jacchus) with bilateral transections of the anterior temporal stem, amygdala and fornix were unable to relearn a 2-choice object discrimination first learnt prior to surgery, and were very severely impaired at relearning a concurrent object discrimination task which they had learnt and relearnt prior to surgery, indicating that they had a dense retrograde amnesia. They also had difficulty learning new visual object discriminations but were only mildly impaired on spatial learning. When tested on new learning of concurrent discriminations 8 to 10 weeks after surgery, three operated monkeys were unable to reach criterion in 400 trials while the remaining two operated monkeys performed within the normal range. The operated monkeys were subsequently shown to be impaired on acquisition of shape discriminations using black objects. These anterograde effects suggest that the impairment runs mainly in the domain of visual analysis. The monkeys also exhibited many of the features of the Klüver-Bucy syndrome. Histological analysis indicated that in addition to cutting some of the subcortical temporal lobe efferent pathways, the surgical procedures had cut the cholinergic afferents to the temporal neocortex, entorhinal cortex, and hippocampus. In a second experiment we found that treatment with the cholinergic agonist pilocarpine, which is effective in monkeys with specific cholinergic lesions, was unable to remediate the lesion-induced impairments. This suggests that transection of the non-cholinergic afferents, or the temporal lobe subcortical efferents, contributed to the behavioural syndrome and the learning and retention deficits seen in these monkeys.

Acetylcholinesterase↗
PubMed2006

The anatomy of the vestibular nuclei.

The vestibular portion of the eighth cranial nerve informs the brain about the linear and angular movements of the head in space and the position of the head with respect to gravity. The termination sites of these eighth nerve afferents define the territory of the vestibular nuclei in the brainstem. (There is also a subset of afferents that project directly to the cerebellum.) This chapter reviews the anatomical organization of the vestibular nuclei, and the anatomy of the pathways from the nuclei to various target areas in the brain. The cytoarchitectonics of the vestibular brainstem are discussed, since these features have been used to distinguish the individual nuclei. The neurochemical phenotype of vestibular neurons and pathways are also summarized because the chemical anatomy of the system contributes to its signal-processing capabilities. Similarly, the morphologic features of short-axon local circuit neurons and long-axon cells with extrinsic projections are described in detail, since these structural attributes of the neurons are critical to their functional potential. Finally, the composition and hodology of the afferent and efferent pathways of the vestibular nuclei are discussed. In sum, this chapter reviews the morphology, chemoanatomy, connectivity, and synaptology of the vestibular nuclei.

Animals↗
PubMed1995

Expression of the conditioned NK cell activity is beta-endorphin dependent.

We are interested in identifying the pathways which are responsible for triggering the conditioned enhancement of natural killer (NK) cell activity. Earlier studies have suggested that central opioid(s) are involved in eliciting the expression of the conditioned NK cell activity. The purpose of this study was to identify the central opioid peptides that allow the central nervous system (CNS) to communicate with the immune system. Mediators that activate the efferent pathway of communication between the CNS and immune system was examined by injection of the mediator via the cisterna magna (CM). Conditioning was used as a tool to show that the bi-directional communication between the CNS and the immune system does take place. We found that beta-endorphin but not dynorphin could stimulate NK cell activity, when beta-endorphin or dynorphin was injected into the CM. In addition, when anti-beta-endorphin or anti-dynorphin antibody was injected into the conditioned animals via CM the conditioned response was blocked by anti-beta-endorphin but not by anti-dynorphin antibody. These observations suggest that beta-endorphin appears to be one of the signals that is induced in the brain at the CS recall step of the conditioned response to trigger the elevation of NK cell activity.

Animals↗
PubMed1986

Horizontal knife cuts either ventral or dorsal to the hypothalamic paraventricular nucleus block testicular regression in golden hamsters maintained in short days.

The possible involvement of efferent pathways from the suprachiasmatic nucleus (SCN) in the photoperiodic regulation of reproduction was studied by measuring the testis size of hamsters bearing a horizontal knife cut either ventral or dorsal to the hypothalamic paraventricular nucleus (PVN) that were transferred from photostimulatory long days (light:dark (L:D) 14:10 h) to non-stimulatory short days (L:D 6:18 h). Knife cuts placed either ventral or dorsal to the PVN blocked testicular regression induced by exposure to short days. These results indicate that efferent fibers running dorsally from the SCN to the PVN are involved in relaying photoperiodic information from the SCN to the PVN. Furthermore, recently-defined efferents that leave the PVN dorsally and terminate in the spinal cord appear to be responsible for relaying seasonal information about day-length to the pineal-reproductive axis of hamsters.

Animals↗
PubMed1988

Retrograde neuronal labelling and double-staining immunohistochemistry of tachykinin- and calcitonin gene-related peptide-immunoreactive pathways in the carotid sinus nerve of the guinea pig.

The origin of tachykinin- and calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerve fibres in the guinea pig carotid body and carotid sinus was determined by retrograde labelling of the carotid sinus nerve with Fluoro-gold and immunohistochemical double staining with fluorescein- and rhodamine-conjugated second antisera. Fluoro-gold-labelled perikarya with characteristic features of primary sensory neurones were numerous in the glossopharyngeal (petrosal) ganglion and occurred rarely in the closely attached superior vagal (jugular) ganglion. An efferent pathway from the brainstem could not be detected. Co-existence of tachykinin- and CGRP-LI was observed in 25-47% of labelled sensory neurones; less than 1% of Fluoro-gold-containing perikarya were exclusively stained by CGRP antiserum. Co-existence of tachykinin- and CGRP-LI was also demonstrated in nerve fibres of the carotid body and carotid sinus. Somatostatin-, cholecystokinin- and dynorphin-LI did not co-exist with tachykinin-LI in these fibres. Thus, tachykinin/CGRP-LI fibres in the carotid presso- and chemoreceptive areas exhibit a peptide pattern being generally characteristic for sensory fibres supplying great vessels in the guinea pig. In view of the present findings doubt is raised as to a primary involvement of these fibres in presso- or chemoreception, although a modulatory influence on these specific functions appears to be likely.

Animals↗
PubMed1985

The hepatic vagus nerve and the neural regulation of insulin secretion.

Despite considerable evidence that vagal neural efferent pathways between brainstem and pancreatic islets may alter the secretion of insulin, afferent pathways which might affect this system have received little attention. In the present work we have examined the effects on plasma insulin concentration of several treatments designed to alter the neural activity of the hepatic vagus nerve, a major afferent pathway between the liver and the medulla. The hepatic vagus nerve was acutely sectioned or stimulated electrically in separate experiments in rats. In a third experiment, glucose or 3-O-methylglucose was given ip to stimulate or inhibit, respectively, the hypothetical hepatic glucoreceptors. The effects of these treatments were assessed by measuring arterial or portal plasma insulin concentrations. Anesthesia and its possible secondary inhibitory effects on insulin secretion were avoided by a spinal sectioning of the rats in the cervical region, before experimentation. Acute section of the hepatic vagus nerve between the liver and the main anterior vagal trunk caused an increase in both arterial and portal plasma insulin concentrations. Stimulation of the central end of the nerve suppressed the concentration of the hormone in both the arterial and portal plasma relative to sham-stimulated controls. Section of the celiac vagal branches to the pancreas abolished these changes. Intraperitoneal glucose enhanced arterial insulin more in sham-vagotomized than in hepatic-vagotomized rats. After 3-O-methylglucose was given ip, the response was the opposite: insulin rose more in the arterial plasma of the hepatic-vagotomized animals than in those sham vagotomized. These results suggest that the hepatic vagus nerve plays a role in the regulation of insulin secretion. They are consistent with the hypothesis that afferent fibers in this nerve exert a tonic inhibition on the brainstem centers of an efferent vagal pancreatic neuroendocrine system.

3-O-Methylglucose↗
PubMed1975

Primate models of postural disorders.

Dorsal column lesions in the high cervical region of the monkey result in severe defects of movements projected into space and contactual orienting reactions of the forelimbs. The hindlimbs are less affected provided a pathway through the lateral columns, Morin's tract, remains intact. Interruption of this pathway results in a defect of hindlimb function similar to that of the forelimbs. Cerebellar ablations in monkeys result in postural and movement disorders, including hypotonia of limb extensor muscles. An important mechanism underlying the hypotonia is a depression of the responses to muscle extension of spindle primary afferents owing to a decrease of fusimotor activity. In the decerebellate animal abnormalities of limb trajectory during active movements projected into space (cerebellar "dysmetria") appear to result principally from dysfunction of systems separate from the peripheral fusimotor efferent-spindle afferent reflex arc. Precentral cortical ablation results initially in a contralateral hypotonic hemiparesis, later in a hypertonic hemiparesis. A depression of the responses of muscle spindle afferents occurs during the hypotonic phase, but during the hypertonic phase spindle function returns to normal levels. Accordingly a depression of fusimotor function appears to be important in the hypotonic phase of hemiplegia; however, there is no evidence that an enhancement of fusimotor function underlies the hypertonic phase. Bilateral section of the medullary pyramids results in an enduring hypotonic paresis. Abnormalities of contactual orienting responses of limbs are similar to those following dorsal column lesions. Responses of spindle primary afferents are depressed during the initial stages after acute pyramidotomy, then approach but do not reach normal levels. It is concluded that the dorsal columns constitute an afferent, and the pyramidal tracts an efferent, pathway important in oriented contactual reactions of the limbs. The hypotonia resulting from cerebellar lesions, precentral ablation, and pyramidal tract section stems, at least in part, from a depression of the fusimotor innervation of muscle spindle afferent activity.

Animals↗