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P Strata

Publications and source records attributed to P Strata.

At least 55 records · Page 3Linked to original sources

Adaptation and habituation of the vestibulo-ocular reflex in intact and inferior olive-lesioned rats.

The gain of the vestibulo-ocular reflex (VOR) of intact pigmented rats was adaptively modified by training protocols that created a visual-vestibular conflict. For training, head restrained animals were oscillated on a turntable in front of an optokinetic pattern projected onto a cylindrical wall. The optokinetic pattern either moved the same amplitude with the animal ("in-phase": 0.05 Hz +/- 20 degrees/s) or opposite in direction ("out-of-phase": turntable and pattern 0.05 Hz +/- 10 degrees/s each). VOR responses were tested in darkness before and after each 8 min training period for a duration of 40 min. During "out-of-phase" training the gain of compensatory eye movements measured in light was close to 2 from the beginning on and the VOR tested in darkness increased in gain progressively from 0.48 (+/- 0.12) to 0.9 (+/- 0.3; P less than 0.05) in 5 out of 7 rats. Two rats did not adapt their VOR gain. Phase values decreased slightly by about 10 degrees. During "in-phase" stimulation compensatory eye movements were almost completely suppressed (gain close to 0) from the beginning on and the VOR tested in darkness decreased gradually in gain from 0.62 (+/- 0.17) to 0.13 (+/- 0.1; P less than 0.001) in all 6 trained rats. Phase values decreased in parallel from 151 degrees to 119 degrees (P less than 0.01). The effectiveness of the "in-phase" training paradigm in the absence of compensatory eye movements indicates that retinal image slip is the relevant signal for adaptation. In seven rats with histologically verified almost complete inferior olive (IO) lesions (chemically induced at least 45 days prior to training), "out-of-phase" and "in-phase" stimulation evoked compensatory eye movements with gains comparable to those in intact rats. VOR parameters measured in darkness were altered with respect to those of control rats. Gain differed extremely between individuals and phase lag re acceleration was in all IO-lesioned rats larger than in intact rats. The time constant of the VOR in response to table velocity steps was significantly longer (17 s +/- 4) than in intact rats (11 s +/- 3). Training did not alter the gain of the VOR in 5 out of 7 IO-lesioned rats. One rat increased its gain during "out-of-phase" training in the first, but not during a second training session (and not during "in-phase" training) and another rat decreased its gain during "in-phase" training (but not during "out-of-phase" training).(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

The rat olivocerebellar system visualized in detail with anterograde PHA-L tracing technique, and sprouting of climbing fibers demonstrated after subtotal olivary lesions.

The rat olivocerebellar climbing fiber system has been investigated at the light and electron microscopic level with anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) tracing. From PHA-L Injections in different parts of the inferior olive labelled axons could be traced to the contralateral cerebellum. Arriving in the deep cerebellar white matter, the olivocerebellar axons ran around and through the cerebellar nuclei. Plexuses of labelled terminal fibers appeared in the cerebellar nuclei, and the density of this innervation was estimated to 1-4 million varicosities per mm3. Ultrastructurally, these boutons engaged in asymmetric synapses with small dendrites. Bundles of labelled fibers continued into the folial white matter, and terminated as climbing fibers in sagittal zones of the cerebellar cortex. Both the cortical and nuclear terminations of the olivocerebellar system are strictly topographically organized. The plasticity of climbing fibers was studied after partial lesions of the inferior olive induced by 3-acetylpyridine. One to 6 months after the lesion, surviving climbing fibers demonstrated extensive sprouting. The newly formed axons originated from parent climbing fiber plexuses, grew in the direction of parallel fibers, and formed terminal plexuses around several neighbouring Purkinje cells. As normal climbing fiber terminals, these terminals formed asymmetric synapses with spines of proximal Purkinje cell dendrites, and evidence by Benedetti et al. (1983) shows that the regenerated innervation is electrophysiologically functional. It is suggested that denervated Purkinje cells release a trophic substance, which stimulate surviving climbing fibers to sprouting, axonal growth and synapse formation.

Animals↗

Effects of ethanol and imidazobenzodiazepine Ro 15-4513 on spontaneous saccades of the pigmented rat.

The present study was aimed at investigating the alterations of the spontaneous saccadic eye movements of pigmented rats following ethanol administration. In addition we have studied the efficacy of the imidazobenzodiazepine Ro 15-4513 in reversing the effects of alcohol on saccades. The horizontal component of spontaneous eye movements was recorded by means of the magnetic field search coil technique on 11 head-restrained, pigmented rats. After the intraperitoneal injection of ethanol (1 g/kg) spontaneous saccades showed: i) a backward post-saccadic drift, with an exponential-like time course (time constant 100-150 ms); ii) a remarkable reduction of mean saccadic amplitude, up to 37% of control; iii) a significant decrease of peak velocity, which was reduced to about 80% of control. All these effects appeared and developed within a few minutes after the administration and were still present one hour later. When Ro 15-4513 (5 mg/kg) was injected i.p., 15 min after ethanol, the post-saccadic drift amplitude was immediately reduced and the drift was completely abolished within about 30 min. Mean saccadic amplitude returned to control values within a few minutes and was then steadily maintained for the following period examined (30 min). On the contrary, peak velocity showed only a slight tendency to recover which never was significant. When the same dose of Ro 15-4513 was injected alone there was no post-saccadic drift. However, mean saccadic amplitude increased, almost immediately, up to 160% of control. Its value showed a slight constant decrease in the following 30 min. Peak velocity was only slightly increased (up to 106% of control), but never was significantly different from control. Our results show that ethanol induces a remarkable impairment in the performance of spontaneous saccades. The imidazobenzodiazepine Ro 15-4513 is able to reverse completely only some of the alcohol-induced alterations, i.e. the post-saccadic drift and the reduction of saccadic amplitude, while it fails to counter efficiently the reduction of peak velocity. Ro 15-4513 exerts an intrinsic action, which is opposite to that of ethanol, on some of the saccadic parameters we have examined.

Animals↗

Antagonist action of imidazobenzodiazepine Ro 15-4513 on ethanol-induced alterations of saccadic eye movements in the pigmented rat.

Following an intraperitoneal injection of ethanol (1 g/kg), spontaneous saccades performed by pigmented rats showed a backward post-saccadic drift which was still present 45 min after the administration. When 5 mg/kg of Ro 15-4513 were injected, 15 min after ethanol, there was an immediate remarkable reduction in post-saccadic drift amplitude, with a full recovery in about 30 min after Ro 15-4513 administration. This drug is thus able to reverse the effect of ethanol and to restore effectively a mechanism of motor integration.

Animals↗

Dynamic characteristics of optokinetically controlled eye movements following inferior olive lesions in the brown rat.

1. The inferior olive was destroyed by the drug 3-acetylpyridine in brown rats. Spontaneous and optokinetic eye movements in response to constant-velocity rotation (5-80 deg/s) or sinusoidal oscillations (0.05 and 0.1 Hz with 15 deg/s peak velocity and 0.3, 0.5, 1.0 and 2 Hz with 5 deg/s peak velocity) of the visual surround were recorded 4-6 days, 40-50 days and 3-4 months after the lesion using the magnetic search coil technique. 2. Persistent oculomotor deficits were observed in rats with a lesion of more than 97% of inferior olive neurones. In cases with a less complete lesion, no or only transient deficits were observed. In these latter cases the bulk of surviving neurones was located in the caudal half of the inferior olive, which includes the dorsal cap of Kooy. 3. Eye position holding after saccadic gaze shifts in the light was strongly deficient, showing pronounced postsaccadic centripetal drift for several hundred milliseconds. Similar deficits were observed in slow-phase components following quick phases of optokinetic nystagmus. In the dark, eye position holding was also deficient. 4. Closed-loop gains of optokinetic step responses obtained from rats with inferior olive lesions could be as good as those obtained from control animals. There was, however, a trend towards smaller gain values over the range of stimulus velocities tested. The duration of optokinetic after-nystagmus was not changed. 5. The initial fast rise of slow-phase velocity of optokinetic step responses was reduced by about 30-50%, showing no recovery in the follow-up experiments up to 3-4 months after the lesion. 6. Optokinetic responses to sinusoidal oscillations of the visual surround exhibited an increasing drop in gain for frequencies between 0.1 to 0.5 Hz. In the range of 0.5-2.0 Hz gain was only about 0.2 compared to 0.7-0.8 in control animals. Phase lag of sinusoidal responses was shifted to larger values by about 25-35 deg for frequencies increasing from 0.1 to 0.5 Hz. At 1.0 Hz phase shift was reduced to about 15 deg and at 2.0 Hz no significant change in phase was observed. Both gain and phase of sinusoidal responses showed some recovery when tested 3-4 months after inferior olive lesion. 7. The results suggest that inferior olive lesions impair velocity-to-position integration, mainly as a consequence of the missing climbing fibre input to the cerebellar flocculi.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Morphology of Purkinje cell axon terminals in intracerebellar nuclei following inferior olive lesion.

We have examined the ultrastructural changes of axons and synaptic boutons in the intracerebellar nuclei of the rat at 3 days to one year after inferior olive lesion performed by means of electrocoagulation or 3-acetylpyridine injection. A large number of preterminal segments and axons terminals undergoes remarkable ultrastructural changes after total or subtotal olivary lesion. Large membrane bound vacuoles and clusters of small synaptic vesicles characterize a good number of these terminals at 3 days up to one month after the lesion. Tightly packed tubules and cisternae of smooth endoplasmic reticulum appear during the first week in an increasing number of axon terminals. Boutons with large whorled bodies formed by smooth membranes increase in number during the second half of the first month and further increase in density until the sixth month. They are still present in large amounts at one year. Immunoreactivity for 3',5'-guanosine-phosphate-dependent protein kinase, which is specific for Purkinje neurons, can be detected in the axons and synaptic terminals displaying the ultrastructural changes described above. These results are discussed in relation to a possible trophic action of the climbing fibers on the Purkinje cells. We suggest that, at least in part, these alterations may be the consequence of the intense Purkinje cell hyperactivity which is present for up to one month from inferior olive lesion.

Animals↗

Influence of inferior olive on flexor reflex activity.

In Wistar rats we have studied the effect of inferior olive lesion or activation on the threshold of a flexor reflex elicited by a nociceptive stimulus applied to the hindpaw. When the inferior olive is lesioned by means of 3-acetylpyridine, the threshold value is significantly decreased. A recovery occurs in 3-4 weeks. When the inferior olive is activated by means of harmaline, the threshold value is significantly increased. These experiments suggest the inferior olive activity exerts an inhibitory effect on flexor reflex activity. The recovery of the threshold value depends, probably, on the plastic reorganization of the cerebellar circuits, which occurs after inferior olive lesion.

Animals↗

Metabolic activity of intracerebellar nuclei in the rat: effects of inferior olive inactivation.

Metabolic activity of the intracerebellar nuclei during cryoinactivation of the inferior olive was studied in the anaesthetized rat by using the 14C-2-deoxyglucose method. Single unit recording of Purkinje cells was simultaneously monitored in the cerebellar cortex. Local inactivation in the inferior olive resulted in regional suppression of complex spike discharges in the cerebellar cortex. An increased metabolic activity was observed in the cerebellar nuclei contralateral to the cryoinactivation site correlating the somatotopically arranged olivo-cerebello-nuclear circuit. This increase was shown to be due specifically to inactivation of the inferior olive, since it was not obtained in a rat in which the inferior olive was previously destroyed by neurotoxic doses of 3-acetylpyridine. The results are interpreted as being due to an increased presynaptic activity of the terminals of the Purkinje cells which fire simple spikes at high rates after climbing fibre deafferentation.

Animals↗

Inferior olive inactivation decreases the excitability of the intracerebellar and lateral vestibular nuclei in the rat.

In rats under sodium pentobarbitone anaesthesia the inferior olive region has been reversibly inactivated by applying a cooling probe to the ventral surface of the medulla. Unitary activity has been recorded from the fastigial, interpositus and Deiters nuclei. Identification of units was based on the presence of a dye spot, left by the recording micropipette. In the Deiters nucleus, an additional criterion of identification was the antidromic activation from spinal cord stimulation. Following cooling of the inferior olive of one side, we have observed suppression of the activity of all the fourteen Deiters neurones and of seventeen out of twenty neurones recorded from the intracerebellar nuclei. In two out of seven Deiters neurones tested the antidromic invasion elicited by spinal cord stimulation was suppressed. In rats, whose inferior olive was previously destroyed, cooling of the inferior olive region was not followed by the powerful depression of spike activity seen in the vestibular and cerebellar nuclei cells in the intact rats. These results indicate that the olivocerebellar system is very important in regulating the level of excitability of the subcerebellar structures and therefore in controlling both postural mechanisms and the processing of information relating to sensorimotor integration.

Animals↗

The inhibitory effect of the olivocerebellar input on the cerebellar Purkinje cells in the rat.

1. In rats under Nembutal anaesthesia the inferior olive region has been reversibly inactivated by applying a cooling probe to the ventral surface of the medulla. Simple and complex spike activity has been recorded from Purkinje cells of the cerebellar cortex.2. Following cooling of the inferior olive of one side we have observed a remarkable increase of the simple spike activity in all the twenty-two Purkinje cells, showing a disappearance of the complex spike activity.3. In some rats two Purkinje cells were recorded simultaneously from each side of the cerebellar cortex. Following cooling of the left inferior olive the effect on the Purkinje cell was observed only or predominantly on the contralateral cerebellar cortex.4. In a group of animals the inferior olive has been destroyed by 3-acetylpyridine 4-221 days before the recording session. Cooling of the inferior olive region was not accompanied by any significant and consistent increase in the spike activity of presumed Purkinje cells of the contralateral cerebellar cortex.5. These results indicate that the remarkable increase of the simple spike frequency following cooling of the inferior olive region is due specifically to the suppression of the activity of the olivocerebellar neurones.6. Only a small amount of the simple spike frequency increase is attributable to the removal of the post-climbing fibre pause.7. In some lesioned rats recording was made from Purkinje cells, which showed complex spikes due to the few surviving inferior olive cells. In these Purkinje cells cooling of the inferior olive region was accompanied by a disappearance of the complex spike and by a small increase of the simple spike frequency of discharge. Such an increase is mainly attributable to the removal of the post-climbing fibre pause.8. These results suggest that a given Purkinje cell is not only under the inhibitory influence of its own climbing fibre, but also of other olivocerebellar neurones, probably through climbing fibre collaterals to the cerebellar cortical interneurones.9. It is suggested that one role of the olivocerebellar system is to exert a powerful tonic inhibitory action on the Purkinje cells and consequently to exert a significant control on the excitability of the subcerebellar centres.

Action Potentials↗

Functional aspects of the inferior olive.

A review is presented of a series of recent experiments aimed at studying the effects of irreversible lesion and of reversible inactivation of the inferior olive. Following a permanent lesion of the inferior olive, no alteration has been found: i) in the morphology of the synapse between Purkinje and Deiters neurones, and ii) in the inhibitory properties of the three types of cells of the cerebellar cortex innervated by the olivocerebellar pathway: the Purkinje, the Golgi and the basket cells. Following reversible inactivation of the inferior olive of one side by cooling, a remarkable increase of the simple spike activity has been found in all the Purkinje cells showing a disappearance of the climbing fibre activity. This effect is likely mediated, at a large extent, by climbing fibre collaterals through corticocerebellar interneurones. The same reversible inactivation of the inferior olive induces a drastic reduction of the activity in the cells of intracerebellar and vestibular nuclei. These experiments don't provide support for a trophic function of the inferior olive on its target neurones. They suggest that this nucleus exerts a very powerful tonic inhibitory action on Purkinje cells and consequently a control on the excitability of intracerebellar and subcerebellar centres. Such a control is likely important for the processing of informations through the cerebellum and therefore for the control of motor activities.

Action Potentials↗

Are the climbing fibres essential for the Purkinje cell inhibitory action?

Following an almost total chemical lesion of the inferior olive, the inhibitory control of the cerebellar Purkinje cells upon their target neurones, mainly in Deiters nucleus, remains practically unchanged. This result is at variance with some recent findings having important implications in the cerebellar theories of motor learning.

Animals↗

On the origin of the climbing fibres of the cerebellar cortex.

Unitary climbing fibre activity has been systematically recorded in the rabbit cerebellar cortex at the level of the Purkinje cell layer every 100 micron along the longitudinal axis of the folium. In one group of animals, spontaneous activity was identified in 197 out of 204 (96.6%) explored layers, and was uninterruptedly present up to 2,400 micron along the folia. In a second group of animals, stimulating electrode were placed in the inferior olive and it was found that spontaneous or evoked climbing fibre activity was absent in only 19 out of 422 explored layers: 377 (89.3%) showed a spontaneous and 396 (93.8%) a short latency evoked activity. If some limitations of the method are considered, it can be concluded that all Purkinje cells receive climbing fibre innervation from cells of the inferior olive. The present experiments support the conclusion that the inferior olive is the unique source of climbing fibres.

Action Potentials↗

The role of the crossed and uncrossed retinal fibres in mediating the horizontal optokinetic nystagmus in the cat.

While the horizontal optokinetic nystagmus (OKN) was studied in cats in which the optic chiasma was completely split thus leaving only uncrossed retinofugal fibers intact it was found that both temporonasal and nasotemporal surround motion generated symmetrical OKN. Similar findings were obtained when one optic tract was sectioned and the eye ipsilateral (uncrossed fibers only) or contralateral (crossed fibers only) to the lesion was covered. It is concluded that in the cat the crossed and uncrossed retinofugal fibers are equipotent in mediating symmetrical OKN.

Animals↗