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Modulation in firing pattern and oscillation in nerve cells of Lymnaea during network reconstruction.

The modulation and reconstruction of the cardio-respiratory neural circuit of Lymnaea stagnalis L. was compared to that of Helix ponatia L. where the input variation and signal molecules were found to have primary importance in network reorganization. From the cardio-respiratory circuit only neurons connected by afferent or efferent pathways to the peripheral chemosensory organ, the osphradium, were used. It was shown that, the general principles of the network reorganization is similar in the two species. The firing pattern of the neurons altered in Lymnaea depending on the input activation or presence of signal molecules in the vicinity of the neurons. The responses of the neurons to the same sensory information, originating from osphradium varied depending on their firing patterns. On central neurones the generation of phasic pattern and/or oscillation was an indicator of network disintegration leading to insensibility to the osphradial sensory inputs. Co-application of signal molecules (5HT, DA, GABA with opioid peptides) to the neurons caused a phasic firing pattern and/or oscillation leading to disintegration of one network and activation of another one. The effect of mu-opioid peptides on GABA-induced and voltage activated ion currents were shown to be the cellular target in reconstruction of neural networks in Lymnaea. The neural network reconstruction in vertebrate brain evoked by signal molecules can be compared to that observed in the identified network of Lymnaea stagnalis making this latter a useful model in further studies, too.

Animals↗

Polar innervation of enteric non-cholinergic and non-adrenergic neurons in the isolated guinea-pig ileum.

To study the polarity of the efferent pathway of the myenteric plexus, recordings were made of the mechanical activity of the longitudinal muscle of isolated guinea-pig ileal segments upon stimulation with an electrical field around the myenteric plexus contained within strips of longitudinal muscle (LM-MP) continuous with each end of ileal segment. The amplitude of the contractile response to stimulation of the anal LM-MP was always larger than that to the oral LM-MP. After cholinergic and adrenergic transmission was suppressed by atropine (10 microM) and guanethidine (1 microM), and the tone of the segment was enhanced by histamine (1 microM), the LM-MP stimulation produced non-cholinergic, non-adrenergic (NCNA) ascending contraction and NCNA descending relaxation. The NCNA contraction, but not the NCNA relaxation, was abolished or reduced by desensitization to substance P. The present results suggest that the NCNA innervation of the myenteric plexus participates in the polar effects observed in the guinea-pig ileum, that the NCNA excitatory response may be mediated at least in part by myenteric substance P neurons, and that the NCNA inhibitory response is mediated by non-adrenergic neurons.

Animals↗

Projections of the optic tectum in two teleost species.

The efferent pathways of the optic tectum have been investigated in the percomorph Eugerres and the berycomorph Holocentrus. A portion of the dorsal-dorsolateral region of the optic tectum was unilaterally resected by suction. The animals were perfused 6-30 days thereafter, and the brains were processed according to a modification (Method 7 in Ebbesson, '70) of the Fink-Heimer ('67) technique for the selective silver impregnation of degenerating axons and terminals. Three groups of fibers emerge from the lesioned region (a) a medial group, which runs towards the midline and terminates in the ipsilateral torus longitudinalis and the contralateral tectum; (b) an ascending group, which enters the dorsocaudal region of the diencephalon and terminates in pretectal cell groups, in the dorsomedial optic thalamic nucleus, and in the nucleus rotundus or prethalamicus; and (c) a descending group, which funnels down into the midbrain tegmentum. Here abundant terminals are given to dorsolateral cell groups and to the nucleus isthmi. A recurrent fascicle leaves the mainstream and ascends to terminate in scattered diencephalic cell groups, in the nucleus geniculatus posterior pars ventralis, and in the nucleus rotundus or prethalamicus. The bulk of descending fibers then forms an ipsilateral bundle, which gives terminals to the lateral reticular formation of mesencephalon and rhombencephalon, and a contralateral (i.e., the predorsal) bundle, which terminates in the medial reticular formation of mesencephalon and rhombencephalon.

Animals↗

A comparative study of the behavioral deficits following lesions of various parts of the zebra finch song system: implications for vocal learning.

Song production in song birds is controlled by an efferent pathway. Appended to this pathway is a "recursive loop" that is necessary for song acquisition but not for the production of learned song. Since zebra finches learn their song by imitating external models, we speculated that the importance of the recursive loop for learning might derive from its processing of auditory feedback during song acquisition. This hypothesis was tested by comparing the effects on song in birds deafened early in life and birds with early lesions in either of two nuclei--Area X and the lateral magnocellular nucleus of the anterior neostriatum (LMAN). These nuclei are part of the recursive loop. The three treatments affected song development differently, as reflected by various parameters of the adult song of these birds. Whereas LMAN lesions resulted in songs with monotonous repetitions of a single note complex, songs of Area X-lesioned birds consisted of rambling series of unusually long and variable notes. Furthermore, whereas song of LMAN lesioned birds stabilized early, song stability as seen in intact birds was never achieved in Area X-lesioned birds. Early deafness also resulted in poorly structured and unstable song. We conclude that Area X and LMAN contribute differently to song acquisition: the song variability that is typical of vocal development persists following early deafness or lesions of Area X but ends abruptly following removal of LMAN. Apparently, LMAN plays a crucial role in fostering the kinds of circuit plasticity necessary for learning.

Aging↗

The nigral projection to predorsal bundle cells in the superior colliculus of the rat.

Predorsal bundle cells give rise to the major efferent pathway from the superior colliculus to the premotor centers of the brainstem and spinal cord responsible for initiating orienting movements. The activity of predorsal bundle cells is profoundly influenced by an inhibitory pathway from substantia nigra pars reticulata that uses gamma aminobutyric acid (GABA) as a neurotransmitter. The present study examines the morphological basis for this influence of substantia nigra on predorsal bundle cells in the rat. In the first experiments, the laminar distributions of the nigrotectal tract terminals and the predorsal bundle cells were compared. The predorsal bundle cells were labeled by the retrograde axonal transport of horseradish peroxidase from either the decussation of the predorsal bundle or the cervical spinal cord, while the terminations of the pathway from substantia nigra pars reticulata were labeled by anterograde axonal transport from the substantia nigra. Either horseradish peroxidase, wheat germ agglutinin conjugated to horseradish peroxidase, or Phaseolus vulgaris leucoagglutinin were used as anterograde tracers. The results showed that the distributions of both the predorsal bundle cells and the nigrotectal terminals are restricted almost entirely to the intermediate grey layer and that they overlap extensively. Predorsal bundle cells varied in size. Within the areas of maximum overlap, the majority, regardless of size, was closely apposed by nigrotectal terminals. In a second series of experiments, the synaptic contacts between nigrotectal terminals and the tectospinal component of the predorsal bundle were examined in tissue in which both the terminals and the tectospinal cells were labeled for electron microscopy. In the final experiments, the distribution and fine structure of the nigrotectal terminals were compared to those of terminals that had been labeled immunocytochemically with an antibody to glutamic acid decarboxylase, the synthesizing enzyme for GABA. The results showed that nigrotectal terminals contain large numbers of mitochondria and pleomorphic vesicles, and form synaptic contacts with the somas and proximal dendrites of tectospinal cells. These synapses have modest postsynaptic densities. In both their distribution and fine structure, these terminations resemble the glutamic acid decarboxylase immunoreactive terminals that contact tectospinal cells. Taken together, these results support the view that the nigrotectal tract is an important source of GABAergic input to most, if not all, predorsal bundle cells.

Animals↗

Signalling in body-weight homeostasis: neuroendocrine efferent signals.

Whilst a number of neuroendocrine afferent signals are implicated in body-weight homeostasis, the major efferent pathway is the sympathetic nervous system (SNS), which affects both energy expenditure and substrate utilization. Thyroid hormones and their interactions with the SNS may also have a role to play. Some of the variability in resting energy expenditure can be explained by differences in SNS activity, and beta-blockade can reduce energy expenditure and diet-induced thermogenesis in Caucasians. Excess energy intake leads to SNS activation and increased diet-induced thermogenesis. A relationship has also been demonstrated between spontaneous physical activity and SNS activity. In many animal models the SNS activates brown adipose tissue thermogenesis, hence increasing diet-induced thermogenesis and dissipating excess energy as heat. This effect is mediated via beta3-adrenoceptors and activation of an uncoupling protein unique to brown adipose tissue. Homologous proteins have been identified in human tissues and may play a role in human energy expenditure. How the SNS is implicated in this process is unclear at present. beta3-Adrenoceptor polymorphism has been associated both with lower resting energy expenditure in some populations and with reduced autonomic nervous system activity. SNS effects on substrate cycling may also play a role. In the development of obesity the effects of the SNS in promoting lipolysis and fat oxidation are likely to be at least as important as its effects on thermogenesis. beta-Blockade has relatively small effects on energy expenditure, but more pronounced effects on reducing lipid oxidation, so tending to favour fat storage and weight gain. Low lipid oxidation is a risk factor for weight gain, and there is some evidence that low basal sympathetic nerve activity in muscle is associated with this process. Overall, the relationship between SNS activity and obesity is complex, with evidence of low SNS activity occurring in some, but not all, studies.

Animals↗

Efferent projections from the periventricular and medial parvicellular subnuclei of the hypothalamic paraventricular nucleus to circumventricular organs of the rat: a Phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study.

The heterogeneous hypothalamic paraventricular nucleus (PVN) is intimately involved in the regulation of several homeostatic functions. These regulations might, at least partly, be mediated via neuronal projections from the PVN to circumventricular organs outside the blood-brain barrier. To study the efferent projections of the medial and periventricular parvicellular subnuclei of the PVN with particular emphasis on the projections to the circumventricular organs, anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) was applied. Three major efferent pathways and one minor one coursed from the medial and periventricular parvicellular subnuclei to the circumventricular organs. The major fiber projections included a rostral, a lateral, and a dorsocaudal projection tract, whereas the minor projection coursed ventrally. Fibers of the rostral projection were followed to the preoptic area and along the fornix to the subfornical organ. Single fibers originating from this projection coursed further rostrally to the organum vasculosum laminae terminalis. The lateral projection equivalent to the hypothalamo-pituitary tract passed through the lateral hypothalamic area to the median eminence, and nerve terminals were observed throughout the rostrocaudal extent of this structure. A few fibers of this bundle continued into the infundibular stalk and some terminated in the posterior pituitary lobe. Few fibers of the lateral projection descended to caudal pontine levels, where they reached descending fibers of the dorsocaudal projection. The dorsocaudal projection was essentially restricted to midline structures. Along the midline, fibers were followed from the hypothalamus either dorsally through the thalamus to the dorsal part of the third ventricle or caudally alongside the ventricular wall to the mesencephalic periaqueductal grey. The density of fibers decreased along the caudal direction of the neuraxis. The dorsal part of this projection gave rise to terminals in the deep pineal gland and pineal stalk, whereas the caudal part of this projection sent terminating fibers into the area postrema. The minor ventrally directed projection could be followed through the periventricular region to the rostral part of the median eminence. The number of terminals in the circumventricular organs varied. Within the median eminence, a high density of afferents was observed in the entire rostrocaudal extent of the external zone, whereas a low density of fibers was seen in the internal zone. A medium density of afferents was observed in the organum vasculosum laminae terminalis, whereas a relative low density of nerve terminals was observed in the posterior pituitary, the deep pineal gland, the subfornical organ, and the area postrema.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Neuro-ophthalmic manifestations of head trauma.

OBJECTIVE: To describe the neuro-ophthalmic findings in a group of patients with head trauma. MATERIALS AND METHODS: A retrospective chart review of all patients given a diagnosis code of head trauma in the neuroophthalmology unit at Emory University between 1991 and 1999. RESULTS: A total of 326 consecutive patients were reviewed (203 [63%] men and 123 [37.0%] women). Age ranged from 2 to 86 years, with a mean of 30 years. Motor vehicle accident was the most common cause of head trauma, occurring in 195 (59.8%) patients. An abnormal neuro-ophthalmic examination was noted in 185 of 326 patients (56.7%). Loss of consciousness was not associated with any outcome, but the presence of a neuroimaging abnormality, particularly intracranial hemorrhage, was significantly associated with specific neuroophthalmic deficits. CONCLUSIONS: Head trauma causes a number of neuroophthalmic manifestations. The afferent and efferent pathways are vulnerable to traumatic injury, although the efferent system is more commonly affected. Loss of consciousness may not be a reliable predictor of specific neuro-ophthalmic outcomes, but neuroimaging abnormalities may.

Adolescent↗

Effect of TAK-637, a tachykinin NK1-receptor antagonist, on lower urinary tract function in cats.

The effect of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H[1,4]diazocino[2,1g][1,7]naphthyridine-6,13-dione), a tachykinin NK1-receptor antagonist, on lower urinary tract function was investigated in cats. TAK-637 (0.1, 0.3, 1 and 3 mg/kg, i.v.) produced a dose-dependent increase in bladder capacity without any significant reduction in voiding efficiency in decerebrate cats. The maximal increase in bladder capacity was 94%. By contrast, oxybutynin at 1 and 3 mg/kg (i.v.) produced a 18% and 35% increase in bladder capacity, respectively, with a 47% and 45% reduction in voiding efficiency. TAK-637 (3 mg/kg, i.v.) did not inhibit the micturition reflex induced by electrical stimulation of the rostral brainstem near the locus coeruleus, indicating that it does not impair the well-organized micturition reflex (bladder contraction and urethral relaxation). These results suggest that TAK-637 increases bladder storage capability without inhibiting the voiding function of the lower urinary tract, presumably by inhibiting the afferent pathway of the micturition reflex, rather than the efferent pathway.

Animals↗

[Are we sectioning the cochlear efferent system during vestibular neurotomy?].

INTRODUCTION: In addition to sensory neurons which transmit information from the inner ear to the brain, there is a system of efferent feedback fibers, called the olivocochlear system, carrying signals from the brain to the ear. Over the past half-century, the efferent system has been extensively studied in animals and results provided theories as to the functional significance of these efferents: to improve signal-to-noise ratio in the auditory periphery, to mediate selective attention, and to protect the inner ear from acoustic overexposure. The results of several studies conducted in man rely on the study of patients who have undergone a vestibular neurectomy. Indeed, anatomical data show that olivocochlear efferents could travel along or inside the vestibular part of the auditory nerve before reaching the organ of Corti. Therefore, these patients may be considered as an experimental model of unilaterally de-efferented subjects. However, to date, none has reported the existence of olivocohlear efferents in the vestibular section following neurectomy. MATERIALS AND RESULTS: In this study, we present the histological results from 18 vestibular sections and show the absence of olivocochlear efferents. CONCLUSION: These results provide a reason to reconsider the results of previous experiments conducted in similar patients and ask for further studies on the olivocochlear efferents pathways.

Cochlea↗

N1 action potentials in humans. Influence of simultaneous contralateral stimulation.

N1 action potentials, elicited by low-level, 4.0-kHz filtered clicks, were recorded from the ear canals of normal-hearing adults. Responses were recorded at two sensation levels in the presence and absence of a pure tone delivered to the contralateral ear. Waveforms were analysed for changes in amplitude and latency. A significant reduction in the amplitude of N1 was observed following the introduction of the contralateral tone at both FC levels. A concomitant change in latency was not observed. For all subjects, ipsilateral and contralateral signals were below the intensities which resulted in acoustic reflexes and crossover of contralateral signals. These data suggest that the N1 amplitude reduction observed in this study represents inhibitory activity of the efferent auditory pathway.

Acoustic Stimulation↗

[Baroreflexes and congestive heart failure].

Abnormal responses are found in the early stages of heart failure with increased sympathetic and decreased parasympathetic activity, causing peripheral arteriolar vasconstriction and tachycardia respectively. The cardiopulmonary baroreflex may be studied by decreasing venous return ("low body negative pressure") and by measuring vascular resistance forearm. The arterial baroreflex may be studied by changing aortic pressures (by intravenous phenylephrine or nitroglycerin). Orthostatism and the tilt test deactivate the cardiopulmonary and arterial baroreflexes simultaneously. These baroreflexes are impaired in patients with heart failure. Their activation does not cause the usual sympatho-inhibition so contributing to increased sympathetic tone. This dysfunction may result from a change at any point on the reflex pathway: the baroreceptors themselves, the afferent, central and efferent pathways. It is selective as during the cold pressor test, the vasoconstrictor response remains intact. One of the possible mechanisms of baroreflex dysfunction in heart failure is loss of sensitivities of the baroreceptors. This may be multifactorial: structural abnormalities, changes in compliance or functional abnormality. Even if the loss of sensitivity is partially related to a change in compliance, other factors play a role. It is more functional than structural abnormalities because, after cardiac transplantation, the baroreceptors regain their sensitivity within 2 to 3 weeks. Excessive Na-K dependent ATPase activation of the smooth muscle cells of the carotid sinus could lead to hyperpolarization of the cell membrane, so reducing the excitability of the receptor. Aldosterone is one of the factors which could activate the Na-K ATPase, as this hormone directly increases pump activity and favorizes the synthesis of new pumps in the vascular smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System↗

[Psychoacoustic tests: effects of atropine].

The efferent pathways exert a control action on the function of the cochlear nucleus and hair cells. Acetylcholine is the neurotransmitter of the centrifugal system and its action can be blocked by atropine. In order to give a contribution to the knowledge of the function of the efferent bundle and of the cochlea efficiency we examined 10 young normal subjects before and after infusion of 1 mg of atropine i.v. a battery of three psychoacoustical tests (Remote Masking, Critical Ratio and Brief Tone Audiometry). After infusion of atropine we have shown an increase of 0.25 Hz hearing threshold, an increase of RC values and a decrease of RM values. It can be concluded that the pharmacological block of the olivo-cochlear bundle determines a stiffness of outer hair cells and basilar membrane; this finding means that the atropine can inhibit the facilitating activity of the efferent system on the cochlear performance.

Adolescent↗

The genesis of efferent connections from the visual cortex of the fetal rhesus monkey.

The prenatal development of the cortical projections to the dorsal lateral geniculate nucleus (LGN), superior colliculus (SC) and pulvinar was studied by autoradiography of orthogradely transported 3H-proline injected into the occipital cortex of fetal rhesus monkeys aged from embryonic day 63 (E63) to E95. Differentiation of pyramidal neurons situated in the infragranular strata of the cortical plate (prospective layers 5 and 6, which give rise to these efferent projections) was also examined in Golgi preparations prepared from specimens of corresponding embryonic ages. In autoradiographs of the E63 fetus, no radioactive label was seen in subcortical structures. In two specimens injected around E70, label was present in the prospective magnocellular layers of the LGN and within the immediately surrounding cell-poor zones. At these young fetal ages, the presence of topographic order in the corticogeniculate projection could not be determined due to the large size of the injection sites relative to the small cerebral vesicles. By E84 the portion of the prospective parvocellular layers adjacent to the white matter also contained label which was characteristically wedge-shaped and appropriately located with respect to the site of the cortical injection, suggesting that topographic order is established. In the oldest fetus (E95) label in the LGN assumed a configuration similar to that seen in the adult. The cortical projection also invades the SC and pulvinar around E70. In the SC, label was initially confined to the stratum opticum, but by E84 it extended into the superficial gray. Thus, all known classes of efferent pathways from the visual cortex to subcortical structures are present by the middle of the 165-day gestational period in rhesus monkey. The one-month period, E63-E97, during which these efferent visual connections are established is characterized by the considerable growth and increased complexity of the dendritic arborization of pyramidal cells in the infragranular cortical layers of area 17. Thus the development of visual cortical efferents occurs in rough synchrony with the genesis of the afferent pathway from the LGN (Rakic, '76a; '79) and with the onset of morphological differentiation of pyramidal neurons in the infragranular cortical layers.

Animals↗

Cutaneous venodilation in response to systemic hypoxemia in dogs.

Experiments were performed in chloralose anesthetized dogs to test if the saphenous vein (a cutaneous vein) participates in the cardiovascular response to systemic hypoxemia. The saphenous vein was perfused at constant flow with cooled blood (32 degrees C) from the terminal aorta. Sixteen paralyzed (gallamine triethiodide) animals were ventilated with 10% O2 in N2 for 4-min episodes; arterial PO2 was 49 +/- 4 mm Hg after 4 min of ventilation with this gas mixture. Hypoxemia caused a 29% decrease in saphenous vein perfusion pressure (interpreted as a dilation) and an 8% increase in aortic pressure. The hypoxemia induced saphenous venous dilation was abolished by (1) section of the vagus nerves and denervation of the carotid chemoreceptors (afferent pathways), or (2) section of the lumbar sympathetic chain (efferent pathway). These data demonstrate that systemic hypoxemia causes a neurally mediated dilation of the saphenous vein that is dependent upon intact carotid chemoreceptors and/or vagus nerves. It is concluded that saphenous vein dilation is part of the integrated cardiovascular response to hypoxemia in anesthetized dogs. This reflex effect may represent a decompensatory mechanism that compromises cardiac output during hypoxemia in animals with hypothermic extremities.

Animals↗

Neural mechanism of depressor responses of arterial pressure elicited by acupuncture-like stimulation to a hindlimb in anesthetized rats.

The effects of acupuncture-like stimulation of a hindlimb on renal sympathetic nerve activity (RNA) as well as mean arterial blood pressure (MAP) were examined in anesthetized rats. An acupuncture needle (diameter of 160 microns) was inserted into the skin of a hindlimb and underlying muscles to a depth of 5 mm and was twisted at about 1 Hz. Under deep anesthetic condition, in about 70% of trials, acupuncture-like stimulation for 60 s induced a decrease in MAP which was accompanied by a decrease in RNA. Acupuncture-like stimulation applied to the muscles alone, but not to the skin alone, induced inhibition of RNA and MAP. Transection of sciatic and femoral nerves ipsilateral to the hindlimb stimulation completely abolished the responses of RNA and MAP. The hindlimb stimulation excited the femoral and common peroneal afferent nerves. In spinalized animals, the hindlimb stimulation did not produce any changes in RNA and MAP. The results indicate that the decrease in MAP induced by acupuncture-like stimulation of a hindlimb is a reflex response. The afferent pathway is composed of hindlimb muscle afferents while the efferent pathway is composed of sympathetic vasoconstrictors including the renal nerves. Endogenous opioids may not be involved in the present reflex, because an intravenous injection of naloxone, an antagonist of the opioid receptors, did not influence the reflex.

Acupuncture Therapy↗

A simulation study of reflex instability in spasticity: origins of clonus.

Clonus is defined as an involuntary rhythmic muscle contraction that generally occurs in people who have sustained lesions involving descending motor pathways in the neuraxis, and is usually accompanied by other signs of reflex hyperexcitability such as spasticity. This paper hypothesizes that clonus arises when two conditions occur simultaneously: 1) the reflex pathway contains long delay times (implying innervation of distal limb muscles, exacerbated when these muscles display slow twitch properties) and 2) the excitability of the motoneurons is enhanced. This paper tested this dual hypothesis by developing a computer model representing the ankle reflex pathway. This model included the ankle muscles, afferent and efferent pathways, and a monosynaptic spinal link between spindle afferents and motoneurons. Simulations show that as the motoneuron current threshold was reduced (reflecting increased excitability of spinal motoneurons), normal reflex responses became unstable and oscillations developed similar to those observed in spastic patients. In parallel, when we choose reflex delay times typical for distal leg muscles in man, system stability is poor, and oscillations occur readily with increasing motoneuron excitability. As simulated pathway delays are reduced, oscillatory behavior is also reduced, and usually damps out. Conversely, as simulated reflex delays are increased, oscillations increase in amplitude and do not decay. Finally, these two phenomena interact, so that increasing motoneuron excitability will induce reflex oscillations for intermediate loop delays. These findings support the hypothesis that unstable oscillatory behavior, such as the oscillations observed in clonus, will occur when the motoneuron excitability increases in a reflex pathway containing long delays. This change in excitability is mediated by a reduction in motoneuron firing threshold, rather than by an increase in feedback gain. Furthermore, we demonstrate that sustained oscillations occur readily through self reexcitation, which reduces the need to propose that a "central oscillator" must be involved in generating clonus.

Algorithms↗