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Effects of streptozotocin-induced diabetes on bladder function in the rat.

Streptozotocin-induced (STZ, 60 mg./kg. I.V.) diabetic male rats underwent cystometrographic (CMG) and electrophysiologic evaluations under urethane anesthesia (1.2 gm./kg.) to determine whether the neural pathways to the urinary bladder are altered in these animals. Diabetic rats (n = 6) in comparison to controls (n = 8) had significantly greater micturition volumes (3.0 +/- 0.8 ml. vs. 0.7 +/- 0.4 ml., p less than 0.001), bladder compliances (0.51 +/- 0.15 cm. H2O/ml. vs. 0.12 +/- 0.09 cm. H2O/ml., p less than 0.001) and bladder weights (225.2 +/- 21.4 mg. vs. 112.2 +/- 18.0 mg., p less than 0.01). No differences were noted in: 1) the thresholds or conduction velocities of axons in the bladder postganglionic nerves, 2) transmission in the major ganglion or 3) the latencies for firing in the supraspinal parasympathetic reflex pathway to the bladder. However, the supraspinal reflex, which was facilitated by bladder distension in 38% of control rats, was not facilitated in any diabetic rats. Another apparent difference in diabetic rats was the absence of spinal reflex response which was noted in 38% of control animals. This study confirmed that CMG changes in STZ-induced diabetic rats are similar to those observed clinically in patients with diabetic autonomic neuropathy, and in addition raise the possibility that these changes are produced by a defect in autonomic reflexes. It is also clear that alterations of the micturition reflex pathway in diabetic rats are distinct from those associated with another type of enlarged, abnormal bladder induced by bladder outlet obstruction.

Animals↗

A new approach to electromyography of the external urethral sphincter.

Detailed electromyographic investigation of the external urethral sphincter was done as part of a urodynamic evaluation of 119 patients. The sphincter was located by inserting electrodes alongside the urethra. The electromyogram was viewed on an oscilloscope and recorded on paper. Normal and abnormal sphincter electromyograms were defined and the role of sphincter electromyography in urodynamic studies was discussed. It was observed that electromyographic activity does not always correlate with urethral resistance but must be interpreted in conjunction with other urodynamic parameters, such as urethral pressures, urinary flow rates and voiding cystourethrography. In addition, sphincter electromyography provides valuable information to define the various neural pathways involved in micturition and continence.

Electromyography↗

The impact of beta-adrenergic blockade on daily rhythms of melatonin and body temperature of golden spiny mice Acomys russatus.

Beta-adrenergic stimulation induces melatonin synthesis and non-shivering thermogenesis (NST) in rodents. The golden spiny mouse, Acomys russatus is a nocturnal species capable of diurnal activity when coexisting with its congenitor the common spiny mouse A. cahirinus. We have investigated the impact of beta-adrenergic blockade on 6-sulphatoxymelatonin (6-SMT--a metabolite and index of melatonin production) and body temperature (Tb) daily rhythms in male A. russatus. Mice were acclimated to an ambient temperature (Ta) of 28 degrees C, under two photoperiod regimes (16L:8D; 8L:16D). The daily rhythms of Tb and urinary 6-SMT were measured for a period of 30 h at intervals of 4 h. Propranolol (4.5 mg/kg, i.p.) was administered one hour before lights went off (i.e. when beta blockade does not affect NST in this species) and both variables were measured for another 30 h. The beta blocker markedly augmented melatonin output of A. russatus under both photoperiod regimes. The elevation in melatonin secretion was accompanied with an increase in Tb of only 16L:8D-acclimated mice (i.e. shorten duration of melatonin peak). However, in 8L:16D-acclimated mice, a phase advance of about 4 h was noted in 6-SMT daily rhythm. These results indicate that the role of sympathetic innervation in regulation of melatonin synthesis in A. russatus differs from that in the rat. In addition, these data are compatible with the hyperthermic action of melatonin in this species. Therefore, it is suggested that in A. russatus, other neural pathways are involved in its pineal regulation.

Adrenergic alpha-Agonists↗

Tachykinin NK1 and NK2 receptor-mediated control of peristaltic propulsion in the guinea-pig small intestine in vitro.

The tachykinins substance P and neurokinin A are excitatory cotransmitters of cholinergic enteric neurons, their actions being mediated by NK1, NK2 and NK3 receptors. This study examined which of these receptors are part of the neural circuitry of peristalsis. Peristaltic propulsion in luminally perfused segments of the guinea-pig isolated ileum was elicited by a rise of the intraluminal pressure. The pressure threshold at which peristaltic contractions were triggered was used to quantify drug effects on peristalsis, inhibition of peristalsis being reflected by an increase in the pressure threshold. The NK1, NK2 and NK3 receptor antagonists SR-140333, SR-48968 and SR-142 801 (each at 0.1 microM), respectively, had little effect on peristaltic activity as long as cholinergic transmission was left intact. However, both the NK1 and NK2 receptor antagonist (each at 0.1 microM) abolished peristalsis after cholinergic transmission via muscarinic receptors had been blocked by atropine (1 microM) and peristalsis rescued by naloxone (0.5 microM). When cholinergic transmission via nicotinic receptors was suppressed by hexamethonium (100 microM) and peristalsis restored by naloxone (0.5 microM), only the NK2 receptor antagonist (0.1 microM) was able to attenuate peristaltic performance as deduced from a rise of the peristaltic pressure threshold by 106%. The NK3 receptor antagonist (0.1 microM) lacked a major influence on peristalsis under any experimental condition. It is concluded that tachykinins acting via NK1 and NK2 receptors sustain intestinal peristalsis when cholinergic neuroneuronal and neuromuscular transmission via muscarinic receptors has been suppressed. NK2 receptors help maintaining peristalsis once cholinergic neuroneuronal transmission via nicotinic receptors has been blocked, whereas NK3 receptors play little role in the neural pathways of peristalsis.

Animals↗

PET evaluation of bilingual language compensation following early childhood brain damage.

We report a positron emission tomography (PET) study in a 37-year-old, right handed, bilingual (English and American Sign Language) male with left frontal lobe damage, without evidence of language or general intellectual dysfunction. A brain MRI scan demonstrated an atrophic lesion of the left dorsolateral prefrontal, orbital, and opercular cortices extending from the frontal pole to precentral gyrus and including parts of anterior cingulate cortex, due to an probable infantile encephalitis. H(2) (15)O PET scans found evidence of increased right hemisphere activity compared to normal controls during spontaneous generation of narrative in both English and ASL. Neuropsychological data were within normal limits with the exception of visuospatial function. The results suggest the possibility that plasticity, unmasking of neural pathways, and or other adaptations of language function in the right hemisphere may have occurred, and are discussed with regard to the crowding hypothesis.

Adult↗

Neurogenic bladder dysfunction.

The neurophysiology of lower urinary tract function is followed by a discussion of the causes, evaluation, and management of neurogenic bladder dysfunction in children. All forms of injured bladders require early assessment and proper treatment, the basis for which is provided. Clues to what the pediatrician can look for and care for are presented.

Child↗

Vagotomy attenuates effects of L-glucose but not of D-glucose on spontaneous alternation performance.

Two peripheral signaling routes have been proposed to account for the ability of peripheral substances such as glucose to modulate memory processing in the brain. One possible signaling route is by crossing the blood-brain barrier to act directly on brain. A second route involves activation of peripheral nerves with resulting changes in neural activity carried by peripheral nerves to the brain. Because the vagus nerve is a major neural pathway between the periphery and brain, peripherally acting modulators of memory modulators may act via vagal afferents to the brain to enhance memory processing. In the present experiments, systemic injections of either D-glucose or L-glucose, a metabolically inactive enantiomer, facilitated performance of rats on a four-arm alternation task, but at very different doses (D-glucose, 250 mg/kg; L-glucose, 3,000 mg/kg). The enhanced performance seen with L-glucose, but not that seen with D-glucose, was attenuated by vagotomy. These findings suggest that the mechanisms by which these enantiomers act to enhance memory are quite different, with L-glucose acting via vagal afferents but D-glucose acting by other means, including direct modulation of central nervous system (CNS) processes by D-glucose.

Animals↗

Isolated-brain parallels to simple types of learning and memory in Tritonia.

Physiological studies of learning and memory often require reduced nervous system preparations that can be trained by stimulation of neural pathways in a manner that mimics behavioral training. In the isolated brain preparation of the seaslug Tritonia, fictive swimming can be activated with a few electrical pulses applied to the cut end of a nerve, and learning experiments can be simulated with combinations of nerve stimuli. Repeated application of a nerve stimulus produced changes in fictive swimming that resembled habituation and iterative enhancement of multiple components of the swimming behavior. Many repetitions of the nerve stimulus led to fictive swimming failure. Stimulation of another nerve then restored the ability of the original nerve to activate fictive swimming, thus reproducing dishabituation results. Sensitization of threshold and latency were also simulated. Parallels between the behavior and the isolated brain suggest that the neuronal modifications underlying simple types of learning can be induced by nerve stimulation. The activity pattern of interneuron C2 in these experiments suggests that increased C2 synaptic efficacy may underlie sensitization of swimming latency.

Action Potentials↗

Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation.

Challenge of animals with infectious microorganisms is well documented to affect a number of behavioral measures through activation of immune-neural mechanisms. In the present study, the ability of an infectious microorganism to directly alter behavioral responses in the absence of an overt immunologic response was examined. Eight-week-old CF-1 male mice were infected orally with the Gram-negative pathogen Campylobacter jejuni in order to establish a subclinical infection that did not result in immune activation. Microbiological examination of cecal contents revealed the presence of C. jejuni in all infected, but not control, animals 1 and 2 days post-oral challenge. Measurement of interleukin-6 (IL-6) levels and peripheral blood leukocyte populations did not reveal the activation of an overt immune response in 1 or 2 day infected animals as compared to controls. Infected mice demonstrated altered levels of anxiety-like behaviors on the elevated plus-maze as compared to controls on Day 2, but not Day 1, as reflected by a significant decrease in exploratory and an increase in nonexploratory behaviors. The anxiogenic effect of a subclinical infection in the absence of an overt immunologic response suggests that the direct activation of neural pathways by microorganisms may play a role in behavior.

Animals↗

Conditioned taste aversion produced by inhibitors of fatty acid oxidation in rats.

The aversive effects of mercaptoacetate (MA) and methyl palmoxirate (MP) were examined in the present experiment. We used a conditioned taste aversion (CTA) paradigm for Sprague-Dawley rats maintained on a low- or high-fat diet, and determined that MA and MP both produce profound aversions to a novel saccharin solution. Because it is known that the stimulation of food intake brought about by MA administration is blocked by destruction of vagal afferents. we repeated the CTA experiment in control and capsaicin-treated rats. Results show that although the capsaicin-treated rats did not increase food intake after MA administration, the CTA produced by MA remained. Therefore, the neural pathways for the aversive and orexigenic effects of MA are distinct. We conclude that MA and MP are aversive, and that the aversive signal generated by MA does not involve vagal afferents or other fibers damaged by capsaicin.

Animals↗

The relative sensitivities of sensory and motor fusion to small binocular disparities.

Horizontal binocular disparity is the fundamental stimulus for both fusional vergence and stereopsis, but whether common disparity-sensitive mechanisms are involved in both responses is unknown. To determine whether the sensitivities of motor and sensory fusion are interdependent, we studied vergence eye movements and depth discrimination, using stimuli with haplopic binocular disparities, in subjects with normal stereopsis and in subjects with mild to severe stereoanomalies. Our results showed that the subjects' disparity discrimination functions varied from nearly perfect discrimination to chance performance for all of the experimental stimuli. Their sensory functions did not necessarily predict the shape of their motor fusion functions, but in most cases were correlated with the subject's fixation disparities. The results support the conclusion that the stereoanomalies and vergence anomalies that previously have been described for coarse binocular disparities also extend to the small, haplopic binocular disparities. The independence of the response properties of sensory and motor fusion suggests that neural pathways for sensory and motor fusion separate after the initial disparity-selective mechanisms in primary visual cortex.

Depth Perception↗

Time-dependent changes of rod influence on hue perception.

Hue-naming was used in conjunction with a probe-flash procedure to determine the time-course of rod-mediated effects on hue appearance across the spectrum. Two types of rod influence on hue are distinguishable on the basis of differences in both spectral specificity and time course of effect: (1) a "faster" rod influence enhances green relative to red and (2) a "slower" rod influence enhances short-wavelength red relative to green and blue relative to yellow. The results show that there are separable rod hue biases that operate over different time courses and that the overall rod influence on hue appearance depends importantly on the temporal properties of the stimuli, presumably because rods interact in different ways with different portions of the neural pathways that mediate human color vision.

Adaptation, Ocular↗

FPL and sweep VEP to tritan stimuli in young human infants.

Young infants can distinguish red from green without brightness cues which shows that neural pathways processing color information (the 'red-green' color-opponent pathway) are functional early in life. There is some doubt over whether the 'blue-yellow' pathway is functional in young infants. Here, we show that infants behave like tritanopic adults until 2-3 months post-term age. By 3-4 months, infants distinguish tritan stimuli, and therefore, the 'blue-yellow' pathway must be functional by that age. Our sweep visual evoked potentials to identical stimuli, however, are not significantly above noise levels, in disagreement with the behavioral responses. We discuss several possible explanations for the discrepancy.

Adult↗

Posterior fossa syndrome.

Transient mutism is a well-recognized sequela of posterior fossa tumor resection in children. A recent review from our institution indicated that 12 of 142 children undergoing such procedures (8.5%) exhibited transient speech impairment, the largest series of such patients reported to date. Each child had a vermian neoplasm that was approached by division of the inferior vermis (n = 10) and/or superior vermis (n = 3). Seven children had medulloblastomas, three had astrocytomas, and two had ependymomas. None of the affected children had cerebellar hemispheric lesions; in contrast, the incidence among children with vermian neoplasms was 13%. In general, mutism developed 1 to 4 days postoperatively and typically was associated with puzzling neurobehavioral abnormalities. All children had bizarre personality changes, emotional lability, and/or decreased initiation of voluntary movements; nine exhibited poor oral intake; and five had urinary retention. Detailed neuropsychological testing was performed in seven children and confirmed the presence of widespread impairments not only in speech, but also in initiation of other motor activities. These deficits generally resolved during a period of several weeks to months, although two children had residual impairment. Characteristically, affect and oral intake normalized before the speech began to improve. These deficits were noted to correlate with the presence of edema within the brachium pontis bilaterally, although this association was not absolute. The latter observation suggests that there was not a single locus underlying this disorder, but rather that the involved neural pathways may have been impaired at any one of a number of sites within the posterior fossa. Based on the results in our patients and in others described in the literature, we postulate an important role for the cerebellum and/or its afferent and efferent connections in initiating (rather than merely coordinating) speech and other complex motor activities and a potential role for these structures in influencing overall behavior and affective state.

Adolescent↗

Is blindsight in normals akin to blindsight following brain damage?

The aim of this chapter is to discuss evidence bearing on two related issues, namely, first, whether the neural pathways of subliminal perception are the same as those subserving suprathreshold perception. Second, whether the pathways for subliminal perception in normals are similar to those subserving blindsight in brain-damaged patients. As to the former question, the overall balance is in favor of the different-pathway hypothesis while a tentative answer to the second question might be that blindsight is basically similar to subliminal perception in normals. The differences undoubtedly existing between the two conditions depend mainly on the differences in the stimuli used to reveal them.

Animals↗

Sensory control of extraocular muscles.

The role of sensory receptors in eye muscles is not well understood, but there is physiological and clinical evidence for the presence of proprioceptive signals in many areas of the central nervous system. It is unclear which structures generate these sensory signals, and which central neural pathways are involved. Three different types of receptors are associated with eye muscles: (1) muscle spindles, (2) palisade endings, and (3) Golgi tendon organs, but their occurrence varies wildly between species. A review of their organization shows that each receptor is mainly confined to a morphologically separate layer of the eye muscle. The palisade endings - which are unique to eye muscles, are associated with the global layer; and they have been found in all mammals studied so far. Their function is unknown. The muscle spindles, if they are present in a species, lie in the orbital layer, or at its junction to the global layer. Golgi tendon organs appear to be unique to artiodactyls (i.e., sheep and goats, etc.); they lie in an outer distal marginal layer of the eye muscle, called the "peripheral patch layer" in sheep. The specific association between palisade endings and the multiply innervated type of muscle fibers of the global layer has led to the hypothesis that together they may act as a sensory receptor, and provide a source of central proprioceptive signals. But other interpretations of the morphological evidence do not support this role.

Afferent Pathways↗

The magnocellular oxytocin system, the fount of maternity: adaptations in pregnancy.

Oxytocin secretion from the posterior pituitary gland is increased during parturition, stimulated by the uterine contractions that forcefully expel the fetuses. Since oxytocin stimulates further contractions of the uterus, which is exquisitely sensitive to oxytocin at the end of pregnancy, a positive feedback loop is activated. The neural pathway that drives oxytocin neurons via a brainstem relay has been partially characterised, and involves A2 noradrenergic cells in the brainstem. Until close to term the responsiveness of oxytocin neurons is restrained by neuroactive steroid metabolites of progesterone that potentiate GABA inhibitory mechanisms. As parturition approaches, and this inhibition fades as progesterone secretion collapses, a central opioid inhibitory mechanism is activated that restrains the excitation of oxytocin cells by brainstem inputs. This opioid restraint is the predominant damper of oxytocin cells before and during parturition, limiting stimulation by extraneous stimuli, and perhaps facilitating optimal spacing of births and economical use of the store of oxytocin accumulated during pregnancy. During parturition, oxytocin cells increase their basal activity, and hence oxytocin secretion increases. In addition, the oxytocin cells discharge a burst of action potentials as each fetus passes through the birth canal. Each burst causes the secretion of a pulse of oxytocin, which sharply increases uterine tone; these bursts depend upon auto-stimulation by oxytocin released from the dendrites of the magnocellular neurons in the supraoptic and paraventricular nuclei. With the exception of the opioid mechanism that emerges to restrain oxytocin cell responsiveness, the behavior of oxytocin cells and their inputs in pregnancy and parturition is explicable from the effects of hormones of pregnancy (relaxin, estrogen, progesterone) on pre-existing mechanisms, leading through relative quiescence at term inter alia to net increase in oxytocin storage, and reduced auto-inhibition by nitric oxide generation. Cyto-architectonic changes in parturition, involving evident retraction of glial processes between oxytocin cells so they get closer together, are probably a response to oxytocin neuron activation rather than being essential for their patterns of firing in parturition.

Action Potentials↗

Effects of dizocilpine (MK-801) on flash-evoked potentials, body temperature, and locomotor activity of hooded rats.

The present study examined the effects of Dizocilpine (MK-801; a noncompetitive N-methyl-D-aspartate receptor antagonist) on flash-evoked potentials recorded from both the visual cortex (VC) and superior colliculus (SC) of chronically implanted hooded rats. The potentials were recorded at 5, 20, and 35 min following i.p. injections of saline, and of 0.1, 0.3, and 1.0 mg/kg MK-801 on separate days. The amplitude of VC component P1 was unaltered following drug treatment. N1 was increased in amplitude by the 0.1-, 0.3-, and 1.0-mg/kg doses, while two other negative peaks in the VC emerged, beginning with the 0.1-mg/kg dose, to complicate the waveform. One negative peak developed between N1 and P2, while the other effectively split peak P2 (forming P2A and P2B). P2A was depressed at all doses, while P2B was depressed at 0.1 mg/kg but augmented at the 1.0-mg/kg dose. N2 was elevated by the 0.3- and 1.0-mg/kg doses, while P3 was increased in amplitude by all doses. N3 was transiently enhanced by the 0.3-mg/kg dose. SC amplitudes were less affected, with P3 and N4 reduced in amplitude by the 0.3- and 1.0-mg/ kg doses. The latencies of most components in both structures were decreased, often with all doses, but generally at the later recording times. A second experiment demonstrated significant MK-801-induced hyperthermia at all of the above doses, although a higher dose of 3.0 mg/kg MK-801 caused hypothermia. The reduction in component latencies may, therefore, result at least in part from a drug-induced hyperthermia. A third experiment demonstrated MK-801-induced changes in locomotor activity in rats in an open field. The effects were both dose and time dependent. The 0.3-mg/kg dose of MK-801 produced significant increases in the number of line crossings from 20-60 min in comparison to the saline condition. Increases in the number of line crossings with the 1.0-mg/kg dose peaked at 15 min, and then gradually declined. It is unlikely, however, that these changes in movement can account for the effects of MK-801 on evoked potentials. In conclusion, the results show that blockade of the ion channel associated with the NMDA receptor produces profound changes in the activity of the neural pathways that are reflected in the middle components of the flash-evoked potential recorded from the VC.

Animals↗