Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.     

Contribution of vestibular commissural pathways to spatial orientation of the angular vestibuloocular reflex

During nystagmus induced by the angular vestibuloocular reflex (aVOR), the axis of eye velocity tends to align with the direction of gravito-inertial acceleration (GIA), a process we term "spatial orientation of the aVOR." We studied spatial orientation of the aVOR in rhesus and cynomolgus monkeys before and after midline section of the rostral medulla abolished all oculomotor functions related to velocity storage, leaving the direct optokinetic and vestibular pathways intact. Optokinetic afternystagmus and the bias component of off-vertical-axis rotation were lost, and the aVOR time constant was reduced to a value commensurate with the time constants of primary semicircular canal afferents. Spatial orientation of the aVOR, induced either during optokinetic or vestibular stimulation, was also lost. Vertical and roll aVOR time constants could no longer be lengthened in side-down or supine/prone positions, and static and dynamic tilts of the GIA no longer produced cross-coupling from the yaw to pitch and yaw to roll axes. Consequently, the induced nystagmus remained entirely in head coordinates after the lesion, regardless of the direction of the resultant GIA vector. Gains of the aVOR and of optokinetic nystagmus to steps of velocity were unaffected or slightly increased. These results are consistent with a model in which the direct aVOR pathways are organized in semicircular canal coordinates and spatial orientation is restricted to the indirect (velocity storage) pathways.     

Learning-induced plasticity in the medial geniculate nucleus is expressed during paradoxical sleep.

Fear conditioning to an acoustic stimulus produces increases in tone-evoked discharges of neurons in the medial division of the medial geniculate nucleus (MG). This study examined the responses of MG neurons to a conditioned tone presented in paradoxical sleep (PS). After 1 session of habituation to a tone, awake rats underwent conditioning in 3 sessions during which the tone was used as the CS preceding a footshock. Control rats received unpaired presentations of tone and shock. The same tone, which never awakened the animal, was presented during PS following each daily session. Responses of MG neurons to the tone in PS were increased after conditioning. This enhancement was as large as that in waking and was manifested earlier after tone onset than in waking. No change appeared after pseudoconditioning. These results demonstrate that associatively induced plasticity in the MG can be expressed during PS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of cerebellar inactivation by lidocaine microdialysis on the vestibuloocular reflex in goldfish

Vestibuloocular reflex performance and adaptation were examined during vestibulocerebellar inactivation by localized lidocaine microdialysis or injection in goldfish. In the light, eye velocity perfectly compensated for head velocity (Vis-VOR) during sinusoidal yaw rotation (1/8 Hz +/- 20 degrees). In the dark, the reflex (VOR) gain was slightly reduced (gain approximately 0.8-0.9). In neither Vis-VOR nor VOR, was gain altered after 1 h of lidocaine microdialysis in the vestibulocerebellum. Before adaptation of reflex gain, the initial suppression or augmentation of Vis-VOR reflex gain produced by in-phase or out-of-phase visual-vestibular stimulation was also unaffected by cerebellar inactivation. Subsequently, 3 h of adaptive reflex training in either the in-phase or out-of-phase paradigm (acquisition phase) respectively decreased (0.30 +/- 0.09) or increased (1.60 +/- 0.08) VOR gain during artificial cerebral spinal fluid (CSF) microdialysis. However, microdialysis of lidocaine completely blocked adaptive gain changes during a 3-4 h period of continuous application. This effect was reversible because VOR gain changes were produced 1 h after lidocaine was replaced with CSF as the dialysate. After adaptive training, bilateral CSF injections (0.25 microl/side) into the vestibulocerebellum did not alter the normal retention or decay of adapted gain changes during a 3 h period in the dark (retention phase). However, injection of lidocaine into the vestibulocerebellum completely blocked retention of the adapted VOR gain returning the gain to values recorded before adaptation. In contrast to either acute or chronic surgical removal, lidocaine inactivation of the cerebellum by microdialysis did not alter either Vis-VOR and VOR behavior or interactive Vis-VOR performance over a wide range of gain extending from 0.3 to 1.4. Thus short-term VOR motor learning is a dynamic process requiring either continuous operation of brain stem cerebellar loops or, alternatively, modifiable sites within or directly influenced by the cerebellum. Our data supports the latter hypothesis, because the direct brain stem VOR pathways appear to be unaltered after cerebellar inactivation, and, hence, independent of the VOR-adapted state.     

Descending pathways from the medial longitudinal fasciculus and lateral vestibular nucleus to tail motoneurons in the decerebrate cat

A group of 120 male workers, employed in copperworks (mean age = 41.5 years; mean exposure duration = 17,9 years) at workposts with the highest level of exposure to lead, were covered by the study. Blood levels of the following heavy metals were measured in all workers: Pb, Cd, Mn, Cu, Zn, Ca, Mg as well as concentrations of FEP and GSH, SOD activity in erythrocytes, parameters of lipid metabolism: total cholesterol, HDL2- HDL3-cholesterol, triglycerides, lipid peroxides (LPO), and lecithin-cholesterol acyltransferase (LCAT) activity. Mean blood lead level accounted for 251,86 micrograms/l, and mean level of FEP was slightly above normal. That may indicate moderate lead deposits in smelters. Concentrations of other metals remained within normal limits. No significant disturbances in lipid metabolism were observed. Along with expected positive correlation between lead blood level and FEP, a significant negative correlation between lead and cholesterol levels as well as between FEP and serum cholesterol was found. Moreover, a significant negative correlation between FEP and serum LPO, as well as a significant positive correlation between concentration and HDL2-cholesterol level and between FEP concentration and SOD activity in erythrocytes were noted. We believe that unexpected outcome of our investigations could result from the adaptation of healthy smelters to the environmental conditions. It is assumed that further exposure could weak antioxidant mechanisms and lead, in consequence, to the manifestation of symptoms induced by harmful effect of free radicals.     

Monoamines (norepinephrine, dopamine, serotonin) in the rat medial vestibular nucleus: endogenous levels and turnover

The preconcentration of some elements such as Cd, Co, Ni, and V(IV) was modeled in the presence of complexing agents such as citrate and oxalate at high Ca, Mg, and sulfate concentrations on iminodiacetic acid/ethyl cellulose (IDAEC), a chelating cellulose. The effect of the species present in the solution was studied after construction of the species distribution curves using critical, estimated, and measured stability constants. The stability constants of the IDAEC chelates were determined potentiometrically. The constants were calculated or estimated using computer programs. The diagrams calculated in homogeneous media were used for optimization of the flow injection on-line preconcentration for analysis of ultratrace metals in the highly mineralized water "Hunyadi."     

Structural plasticity of optic synapses in the rat suprachiasmatic nucleus: adaptation to long-term influence of light and darkness

Synapses of optic afferents (optic synapses) in the suprachiasmatic nucleus of hooded rats were morphometrically evaluated after exposing the animals to 12 h, 14 days, 2 months, and 8 months of constant light (light rats) and darkness (dark rats). Compared with dark rats, optic synapses from light rats have larger boutons with larger mitochondria, more clear vesicles, fewer dense-core vesicles and front-line vesicles, smaller presynaptic dense projections, a smaller amount of postsynaptic density material, a smaller relative number of Gray-type I (asymmetric) junctions, a greater relative number of Gray-type II (symmetric) junctions, as well as more and larger mitochondria in the postsynaptic dendrites. Junctions of optic synapses are mostly straight, but the small number of positively curved contacts are more flattened in light rats than in dark rats. An age-related increase in the size of presynaptic dense projections was also observed. There are no changes in the sizes of clear and dense-core vesicles, in the size of synaptic junctions and their numerical density in area, and in the unspecific contact area between pre- and postsynaptic elements. The changes in optic boutons are characteristic for activated and relatively disused synapses with a slow, tonic firing rate. It appears that (1) the amount of postsynaptic density material is proportional to the strength of Gray-type I synapses, and that (2) some excitatory optic synapses become inhibitory after long-term activity, whereas some inhibitory synapses turn into excitatory contacts after long-term disuse.     

Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala

The mu-opioid receptor (mu-OR), like most G-protein-coupled receptors, is rapidly internalized after agonist binding. Although opioid peptides induce internalization in vivo, there are no studies that demonstrate mu-OR internalization in response to natural stimuli. In this study, we used laser-scanning microscopy to demonstrate that estrogen treatment induces the translocation of mu-OR immunoreactivity (mu-ORi) from the membrane to an internal location in steroid-sensitive cell groups of the limbic system and hypothalamus. Estrogen-induced internalization was prevented by the opioid antagonist naltrexone, suggesting that translocation was largely dependent on release of endogenous agonists. Estrogen treatment also altered the pattern of mu-ORi at the bright-field light microscopic level. In the absence of stimulation, the majority of immunoreactivity is diffuse, with few definable mu-OR+ cell bodies or processes. After stimulation, the density of distinct processes filled with mu-ORi was significantly increased. We interpreted the increase in the number of mu-OR+ processes as indicating increased levels of internalization. Using this increase in the density of mu-OR+ fibers, we showed that treatment of ovariectomized rats with estradiol benzoate induced a rapid and reversible increase in the number of fibers. Significant internalization was noted within 30 min and lasted for >24 hr after estrogen treatment in the medial preoptic nucleus, the principal part of the bed nucleus, and the posterodorsal medial amygdala. Naltrexone prevented the increase of mu-OR+ processes. These data imply that estrogen treatment stimulates the release of endogenous opioids that activate mu-OR in the limbic system and hypothalamus providing a "neurochemical signature" of steroid activation of these circuits.     

Organization of the medial pulvinar nucleus in the macaque

BACKGROUND: The medial pulvinar appears to subserve the integration of associative cortical information and projects to visuomotor-related cortex. In contrast to the other pulvinar subdivisions, the medial pulvinar is a polymodal structure. Therefore, we studied the structural organization of the medial pulvinar to determine how it differs from the surrounding unimodal nuclei. METHODS: Nissl-stained sections were examined to determine the boundaries of, and the distribution of neuronal sizes within, the medial pulvinar. In addition, Golgi-impregnated neurons were examined and drawn for analysis. Only rhesus monkey specimens were used, and the material had been prepared previously for other studies. RESULTS: Projection neurons have round to oval somata and moderate numbers of primary dendrites that extend for short distances before branching into many secondary branches. Two variations of projection neurons (P1 and P2) were distinguished on the basis of the diameters of their dendritic tree. Both varieties have short dendrites that radiate in all directions. They differ in that P2 cells have longer second tier dendrites than P1 cells. Three types of local circuit neurons, tufted, radiating and varicose, were distinguished on the basis of their dendritic morphology. Four types of afferent fibers were identified. Type 1 afferents form cone-shape terminal arbors. Type 2 afferents are similar to those reported for retinal or cortical terminals. Type 3 afferents are of medium thickness and of an unknown origin. Type 4 afferents are thin and have small varicosities consistent with previously described cortical afferents. Afferent fibers are predominantly oriented along the mediolateral axis of the nucleus. We observed putative contacts between some afferents and local circuit neurons and between local circuit neurons and projection neurons. CONCLUSIONS: Medial pulvinar neurons are generally smaller and rounder than those found in the adjacent pulvinar nuclei. These results provide additional evidence for structural distinctions between thalamic nuclei having different functions. However, the observed differences are subtle. In addition, the data in this report provide morphological evidence that cortical signals are likely to be integrated by means of the circuitry located within the nucleus.     

Response of the hypothalamic neurons to stimulation of the vestibular nerve and lateral vestibular nucleus in rabbits

Effects of single, double, and rhythmic stimulation upon hypothalamic neurons responding to the 1st excitatory phase of lateral vestibular nucleus stimulation, were studied. The data obtained show that activation of some hypothalamic neurons following stimulation of the lateral vestibular nucleus has a monosynaptic character. The findings suggest that ascending afferents from the lateral vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic pathways.     

Induction of long-term receptive field plasticity in the auditory cortex of the waking guinea pig by stimulation of the nucleus basalis.

Learning induces neuronal receptive field (RF) plasticity in primary auditory cortex. This plasticity constitutes physiological memory as it is associative, highly specific, discriminative, develops rapidly, and is retained indefinitely. This study examined whether pairing a tone with activation of the nucleus basalis (NB) could induce RF plasticity in the waking guinea pig and, if so, whether it could be retained for 24 hrs. Subjects received 40 trials of a single frequency paired with electrical stimulation of the NB at tone offset. The physiological effectiveness of NB stimulation was assessed later while subjects were anesthetized with urethane by noting whether stimulation produced cortical desynchronization. Subjects in which NB stimulation was effective did develop RF plasticity and this was retained for 24 hrs. Thus, activation of the NB during normal learning may be sufficient to induce enduring physiological memory in auditory cortex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electromyographic effects of serotonin application into the lateral vestibular nucleus

Electromyographic responses (EMGs) of limb muscles were studied during microiontophoretic application of 5-hydroxytryptamine (5-HT) into the lateral vestibular nucleus (LVN) or the spinal vestibular nucleus (SpVe) of anaesthetized rats. The aim was to ascertain whether the level of 5-HT in these nuclei was able to modulate muscle responsiveness. Increased levels of 5-HT in LVN (and to a weaker extent in SpVe) enhanced the EMGs of proximal extensor muscles and depressed those of flexors. The 5-HT2A receptor antagonist ketanserin, applied into the LVN, prevented 5-HT effects on EMG-evoked responses. It is concluded that 5-HT can modulate the motor output via the vestibulospinal pathway, exerting a differential control over flexor and extensor muscles.     

Development of contrast sensitivity and temporal-frequency selectivity in primate lateral geniculate nucleus

We studied the development of spatial contrast-sensitivity and temporal-frequency selectivity for neurons in the monkey lateral geniculate nucleus. During postnatal week 1, the spatial properties of P-cells and M-cells are hardly distinguishable, with low contrast-sensitivity, sluggish responses, and poor spatial resolution. The acuity of P-cells improves progressively until at least 8 months, but there is no obvious increase in their maximum contrast-sensitivity with age. The contrast sensitivity of M-cells is already clearly higher than that of P-cells by 2 months, and at 8 months of age this characteristic difference between M- and P-cells approaches the adult pattern. There is a major increase in responsiveness during the first 2 postnatal months, especially for M-cells, the peak firing rate of which rises fivefold, on average, between birth and 2 months. Many P-cells in the neonatal and 2-month-old animals did not give statistically reliable responses to achromatic gratings, even at the highest contrasts: this unresponsiveness of P-cells might result from low gain and/or chromatic opponency. The upper limit of temporal resolution in the neonate is low--about one-third of that in the adult. Among M-cells, the improvement in temporal resolution, like that in contrast sensitivity, is rapid over the first 2 months, followed by a slower change approaching the adult value by 8 months of age. The development of contrast sensitivity, responsiveness and temporal tuning are little affected, if at all, by binocular deprivation of pattern vision from birth for even a prolonged period.     

Morphine catalepsy as an adaptive reflex state in rats.

A series of experiments with 56 male Long-Evans rats demonstrated that catalepsy induced by morphine sulfate (20–80 mg/kg, ip) consists of 2 complementary, but opposite, behavioral extremes (rigid immobility and sudden locomotor bursts), each of which could be controlled by distinct classes of external stimuli. When stimuli that involved pain and/or nonnociceptive skin pressure were tonic (continuous), morphine-induced EEG deactivation and behavioral immobility were potentiated, even to the extent that a stimulation-bound reversible coma resulted. In contrast, phasic (discrete stimulation produced behavioral and/or EEG activation. EEG and behavioral rebound effects were observed following stressful (intense, prolonged) stimuli. On the basis of the observed stimulus controls, sensorimotor characteristics, and EEG reactions, it is suggested that similarities may exist between morphine-induced catalepsy and defensive reactions of immobility and escape in drug-free animals (i.e., the adaptive death-feigning reflex). (59 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Optokinetic reflex in squirrel monkeys after long-term monocular deprivation

Horizontal optokinetic nystagmus (OKN) as well as neuronal response properties in the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system (NOT-DTN) were investigated in three monocularly deprived squirrel monkeys. In two monkeys occlusion of one eye was performed at birth (early) and in the third after 7 weeks (late). In adulthood, in early deprived monkeys monocular horizontal OKN tested through the non-deprived eye was symmetrical and in no way different from normal, i.e. stimulation in the temporonasal and nasotemporal direction elicited equal and robust responses. OKN through the early occluded eye, however, was grossly abnormal with low gain and great variability in the consistency of nasotemporal and temporonasal slow phase eye movements. When in the late deprived monkey the non-deprived eye was occluded a strong spontaneous nystagmus developed despite the deprived eye viewing a stationary pattern. The slow phases were directed from nasal to temporal for the deprived eye. When tested through the non-deprived eye all neuronal responses of the NOT-DTN were normal. The deprived eye's influence on NOT-DTN neurons was extremely weak. No neuron with a moderate or even dominant input from the deprived eye was found after early deprivation. In the late deprived case the deficit was not as severe but still the non-deprived eye was clearly dominating the responses in all neurons tested. Velocity tuning of neurons tested through the non-deprived eye was normal and qualitatively corresponded well to slow phase eye velocity in response to equivalent retinal slip during OKN. Through the early deprived eye, however, velocity tuning was extremely poor. It was somewhat better through the late deprived eye. We suggest that the dramatic deterioration in the optokinetic reflex found after long-term monocular deprivation for the amblyopic eye is probably caused by the almost complete loss of retinal and cortical input driven by that eye to the NOT-DTN. These results are discussed in relation to our previous results in cats and reports in the literature for humans with occlusion amblyopia.     

Neuronal loss and plasticity in the supraoptic nucleus in Parkinson's disease

Disturbed circadian control of renal water excretion and blood pressure adaptation in Parkinson's disease (PD) suggest impaired hypothalamic magnocellular neurosecretion. To test the hypothesis that this may relate to specific hypothalamic pathology in PD, we studied morphometrically the neuronal population of the supraoptic nucleus (SON) in PD patients and controls. Neuronal loss in the SON of PD patients was associated with increased somatic, nuclear, and nucleolar size of remaining neurons, suggesting compensatory response of these cells. We conclude that SON pathology is a feature of PD and may account for specific signs of neurohumoral dysfunction.     

Neuroethological studies of reflex plasticity in intact Aplysia..

Multi-unit recording of siphon nerve activity in intact Aplysia californica (a marine gastropod) with chronically implanted cuff electrodes provided a monitor of activity in a central pattern generator, the Interneuron II (Int II) network, which produces large siphon and gill contractions both spontaneously and after tactile stimulation of the siphon. The phase–response curve of the Int II oscillator for single stimuli at different phases of the cycle showed a "refractory" period early in the cycle, after which most stimuli phase advanced the oscillator and caused a short-latency Int II burst and a large contraction. The amplitude of gill withdrawal and the duration of siphon withdrawal in response to different stimulus intensities depended on whether an Int II burst was triggered. Activation of the Int II oscillator transformed the reflex from one that was graded smoothly with stimulus intensity to one in which nearly maximal responses were elicited even by weak stimuli. Entrainment and habituation training both involved monotonous repetition of a stimulus at specific intervals. With repeated siphon stimuli, nearly maximal reflex responses were maintained in intact Ss as long as the Int II oscillator was entrained, whereas habituation was associated primarily with failure to entrain the oscillator. Sensitized Ss showed significantly more triggered Int II burst than did controls. Digital spike-train analysis indicated that individual siphon motoneurons showed significantly increased background activity that often persisted for several minutes. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of neuropeptides in pathogenesis of reflex sympathetic dystrophy

In 1993, a study was undertaken at the Hand Clinics of Loyola University Medical Center in Chicago to investigate the role of the neuropeptides in the pathogenesis of Reflex Sympathetic Dystrophy. All of the patients had recurrent or continuous pain, swelling, and stiffness of one or both extremities following either acute trauma or surgical intervention. All of the patients showed a markedly increased level of bradykinin as well as calcitonin gene-related peptide. The levels of bradykinin were four times as high as the controls. A few showed increased levels of the other neuropeptides. With these results, we agree with Veldman, Goris and others who consider Reflex Sympathetic Dystrophy to be an exaggerated regional inflammatory disorder.     

Role of vestibular information in initiation of rapid postural responses

Successful regeneration of lesioned adult spinal cord in urodele (caudate) amphibians requires the action of injury-responsive ependymal cells (ependymoglia). The epithelial-to-mesenchymal transformation of ependymal cells following transection of the salamander spinal cord and the subsequent reformation of an epithelial tube have been described previously. A complete tissue culture model system has now been devised to study mesenchymal ependymal cells, epithelial ependymal cells, and ependymal/neuronal interactions in vitro. Here, we review critical aspects of substrate and growth factor environments required to produce mesenchymal ependymal cells in culture and present the first culture system for epithelial salamander ependymal cells and central nervous system neurons suitable for cell-cell interaction studies. Critical to ependymal epithelialization in culture is the removal of epidermal growth factor and addition of thrombin. Epithelialization occurs on tissue culture plastic as well as on permeable culture substrates. This culture system can now be used to determine the initial trigger for the ependymal response. A preliminary examination of ependymal/neuronal interactions shows that coculture of mesenchymal ependymal cells and central nervous system neurons prolongs survival of the neurons.