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P Strata

Publications and source records attributed to P Strata.

At least 37 records · Page 2Linked to original sources

Embryonic Purkinje cells grafted on the surface of the adult uninjured rat cerebellum migrate in the host parenchyma and induce sprouting of intact climbing fibres.

By grafting solid pieces of cerebellar anlage onto the surface of the adult rat cerebellum, we have investigated the problem of the interactions between embryonic and adult neurons in an intact brain. A few days after grafting, embryonic astrocytic processes crossed the graft--host interface and radiated into the recipient molecular layer. Several grafted Purkinje cells also migrated into the host brain along such processes as well as adult Bergmann glia. Adult climbing fibres, labelled by means of Phaseolus vulgaris leucoagglutinin (PHA-L), sprouted new collateral branches which terminated on embryonic Purkinje cells at both extra- and intraparenchymal levels. No sign of activation of host astroglia or microglia was evident in the host cerebellum in relation to these processes. Embryonic Purkinje cells which migrated into the host cerebellum developed an adult-like morphology. Intraparenchymal grafts of neocortical embryonic tissue induced conspicuous growth of host olivary axons, characterized by a pattern which was different from that observed following cerebellar grafts. By contrast, when neocortical tissue was placed onto the surface of the recipient cerebellum, graft--host interactions were limited and climbing fibre sprouting was rarely seen. These results show that (i) supernumerary Purkinje cells can penetrate and settle in the adult intact cerebellar cortex, (ii) adult climbing fibres are able to innervate these new targets in the absence of any injury or activation of non-neuronal cells of the adult brain, and (iii) in the absence of damage to the adult brain, the plasticity of adult olivary axons is specifically elicited and controlled by embryonic Purkinje cells.

Animals

Vergence compensation during binocularly- and monocularly-evoked horizontal optokinetic nystagmus in the pigmented rat.

During horizontal optokinetic nystagmus evoked by binocular stimulation in the rat, the slow phases are well-conjugate. The fast phases in the adducting eye are on average about 2 deg greater in amplitude than those of the abducting eye. This causes a transient convergence which is compensated for by a divergent drift within the 100 msec following the fast phase. The amplitudes of these convergence-divergence components fluctuates somewhat from one fast phase to another and their relative amplitudes may differ. As a consequence differences in vergence between successive slow phases may occur. Such differences are usually of small amplitude, but may be as large as 5 deg. When optokinetic nystagmus is evoked by monocular stimulation, the slow phase velocities are different in the two eyes, giving a disjunctive component which is compensated for by a difference in the relative amplitudes and velocities of the fast phases in the two eyes. However, the divergent drift immediately following the fast phases is very similar whatever form of stimulation is employed. It is suggested that during monocularly-evoked optokinetic nystagmus the oculomotor system compensates for the disjunctive component arising during the slow phases by giving a different balance to the pulses of innervation of two eyes, resulting in fast phases of different amplitude.

Animals

Cellular plasticity at the climbing fibre-Purkinje cell synapse as a model of plasticity in adulthood and ageing.

In the adult brain there is a high degree of plasticity which is documented here for climbing fibre terminal arborization impinging upon the proximal Purkinje cell dendrites. Such an arborization presents a more distal compartment, including 90% of branches and varicosities, whose integrity depends on the target and a more proximal compartment which survives to target degeneration. The same terminal arborization enlarges its territory of innervation through collateral sprouting when nearby Purkinje cells are deprived of their climbing fibres or when embryonic Purkinje cells are placed on the surface of an intact cerebellum. In the latter case axonal elongation occurs in the absence of degeneration products and of macrophage/microglia or astrocyte activation. In addition, the embryonic Purkinje cells are able to invade the intact host molecular layer where they develop dendritic arbours which become also innervated by climbing fibre collaterals.

Aging

Effects of inferior olive inactivation and lesion on the activity of medial vestibular neurons in the rat.

In anaesthetized rats, the unitary activity from the medial vestibular nucleus had been recorded during horizontal sinusoidal rotation in the absence of visual stimulation. In the first series of experiments, the inferior olivary nuclei were selectively destroyed by means of 3-acetylpyridine. Unitary activity was recorded three to five days or one month after the lesion. A few days after the lesion, the average spontaneous activity, as well as the peak-to-peak amplitude of the modulation of the medial vestibular neurons during sinusoidal rotation, were significantly lower compared to those recorded in intact rats, and to those recorded one month after the lesion. In the second series of experiments, during reversible cooling of the inferior olive region of one side, in the contralateral medial vestibular nuclei 57% of units underwent a clear decrease in firing rate accompanied by a decrease in the amplitude of modulation. In rats whose inferior olivary nuclei had been destroyed by means of 3-acetylpyridine one month before, or whose cerebellum had been removed, there were few units that showed a decrease of the firing rate and modulation amplitude on cooling the same olivary region. Our experiments show that silencing the activity of the inferior olive causes a decrease both in the spontaneous firing rate and in the amplitude of the response of the vestibular neurons to natural labyrinthine stimulation. These results support the hypothesis that the inferior olive, by changing its firing rate, may regulate on-line the gain of reflexes which are under cerebellar control.

Animals

Regressive modifications of climbing fibres following Purkinje cell degeneration in the cerebellar cortex of the adult rat.

The role of postsynaptic neurons in the maintenance of adult terminal axon arbours was investigated in the rat olivocerebellar system. The degeneration of Purkinje cells, the main target of olivary axons in the cerebellar cortex, was obtained by intraparenchymal application of kainate. The structural features of target-deprived climbing fibres, visualized by Phaseolus vulgaris leucoagglutinin tracing, were examined from two days to six months after the lesion. Following the degeneration of its Purkinje cell, the climbing fibre underwent remarkable regressive modifications involving the disappearance of most of the terminal arborization. Never the less, atrophic arbours still spanned through the molecular layer six months after the lesion. Morphometric evaluations showed that, one week after kainate application, total arbour length was already reduced to 52% of control, whereas the number of branches and of varicosities had both dropped around 40%. This retraction process progressed in the following stages to reach its maximum at about one month after the lesion, when total length was 30% of control and only 10% of branches and varicosities were still present. Only a slight tendency to a further decrease of the values could be detected at longer survival times. Branching pattern analysis revealed that such regressive phenomena mainly involved the distal compartment of the climbing fibres, the one made of fine varicose branchlets, while sparing the proximal thick branches. In addition, the whole process appeared to follow some rather strict guiding principles leading to an ordered branch retraction, from the periphery of the arbour inwards. Finally, in order to rule out the possibility that the observed changes could be due to a direct action of kainate on climbing fibres, we designed an alternative method of killing Purkinje cells by intraparenchymal injection of propidium iodide. The structural features of climbing fibres deprived of their target by such a procedure were very similar to those shown by arbours from time-matched kainate-lesioned animals at both qualitative and quantitative levels. Our results show that target deprivation induces remarkable structural modifications in the climbing fibre, leading to the retraction of most of the arbour. Never the less, the integrity of the Purkinje cell is not necessary for the maintenance of the whole arborization since its proximal compartment is maintained in the molecular layer for several months after target degeneration. It is proposed that the Purkinje cell, most likely by acting through a contact factor, directly controls the formation and the maintenance of the distal climbing fibre branches with their varicosities, which represent the presynaptic compartment of the axonal arbour.

Animals

Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. I. Development of new collateral branches and terminal plexuses.

Cerebellar climbing fibres react by collateral sprouting after subtotal lesions of the inferior olive, and the newly formed branches are able to reinnervate neighbouring denervated Purkinje cells. In the present paper, we used the Phaseolus vulgaris leucoagglutinin (PHA-L) tracing technique to label the climbing fibres and study their plasticity in detail at the light microscopical level. The specific objectives were to study the time course and morphological aspects of their sprouting, to estimate their extent of growth, and to compare the newly formed terminal plexuses with normal climbing fibres. Intraperitoneal injection of 3-acetylpyridine induced degeneration of the majority of the olivary neurones, which terminate as climbing fibres in the cerebellar cortex. Regularly, small numbers of neurones survived in the inferior olive. In the cerebellar cortex scattered surviving climbing fibres were found, which were devoid of any sign of injury. Already 3 days after the lesion, surviving climbing fibres had emitted collateral branches, which elongated for some distance through the molecular layer and ended with a number of varicosities and very fine branchlets. By 7 days, it was possible to recognize new developing arbours which grew in the molecular layer with the same orientation as normal climbing fibres. At longer survival times, extensive terminal arbours had developed and double labelling experiments confirmed that they terminated around the proximal dendrites of Purkinje cells. The newly formed terminal plexuses resembled, in all essential aspects, normal climbing fibres. In addition, from 1 month onward, it was evident that every surviving climbing fibre was able to form several new terminal plexuses reinnervating a number of neighbouring Purkinje cells. The result of this process was the formation of large clusters of newly formed plexuses around the parental arborization. Quantitative estimates indicated that the domain of innervation of single surviving climbing fibres could be increased by more than six times. It is concluded that climbing fibres surviving a subtotal olivary lesion are capable of extensive sprouting, axonal growth, and formation of new terminal plexuses, which resemble normal climbing fibres. Previous electrophysiological evidence indicates that this reinnervation is functional. The high specificity with which sprouting olivary axons reinnervate the proximal Purkinje cell dendrites suggests the existence of precise interactions between the growing fibres and their target. This example of "homotypic" collateral sprouting and reinnervation may thus provide a useful model for the study of nerve-target interactions.

Animals

Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. II. Synaptic organization on reinnervated Purkinje cells.

A salient feature of the cerebellar Purkinje cells is the highly ordered distribution of their excitatory afferents on the dendritic tree. Climbing fibres synapse exclusively on the proximal dendrites, whereas parallel fibres articulate with the distal branches, the so-called spiny branchlets. This input organization is lost following the removal of climbing fibres. Such denervation results in the formation of a large number of new spines on the proximal dendrites, and these become contacted by sprouting parallel fibres, which thereby extend their domain of innervation. We have previously shown that the climbing fibres surviving a subtotal lesion of the inferior olive sprout and reinnervate neighbouring Purkinje cells. In the present ultrastructural study, we have investigated the features of Purkinje cells reinnervated by sprouting climbing fibres. The objectives were to examine the fine morphology of the newly formed synapses and to determine whether the modifications of Purkinje cell morphology and afferent organization are reversed by this reinnervation. Surviving climbing fibres were labelled by the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and immunohistochemically visualized by means of the gold-substituted silver peroxidase technique, 2 and 6 months after 3-acetylpyridine lesions of the inferior olive in adult rats. Sprouting climbing fibres and newly formed arborizations were identified in the light microscope, isolated, and cut in serial ultrathin sections for electron microscopic analysis. The labelled boutons belonging to newly formed terminal plexuses exhibited the typical morphological features of climbing fibre terminals, i.e., a high number of round synaptic vesicles and a few small mitochondria. Most frequently they formed asymmetric synapses on stubby thorns protruding from the proximal Purkinje cell dendrites. In some instances, however, the postsynaptic element consisted of long slender spines or spines showing an atypical morphology. A number of labelled boutons was also in contact with the perikarya of reinnervated Purkinje cells, either articulating with spines or synapsing directly on the smooth somatic surface. The proximal dendrites of denervated Purkinje cells were characterized by large numbers of spines, which were frequently postsynaptic to parallel fibres. By contrast, Purkinje cells reinnervated by the sprouting climbing fibres generally showed a lower number of spines on their proximal dendrites, indicating a reversal of this morphological change. The aberrant parallel fibre input was also decreased on reinnervated dendrites or had completely disappeared. Nevertheless, some reinnervated Purkinje cells showed the persistence of some parallel fibre synapses on their proximal dendrites. On occasion, climbing fibre and parallel fibre boutons synapsed on the same spine.

Aged

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