Climbing Fiber System Research Articles

Anterograde tracing of the rat olivocerebellar system with Phaseolus vulgaris leucoagglutinin (PHA-L). Demonstration of climbing fiber collateral innervation of the cerebellar nuclei.

The olivocerebellar climbing fiber system was investigated in the rat with anterograde Phaseolus vulgaris leucoagglutinin (PHA-L) tracing. The specific objective of the study was to find morphological evidence of climbing fiber collaterals innervating the cerebellar nuclei. Small iontophoretic injections of PHA-L were placed in different parts of the inferior olivary complex, and labelled olivocerebellar fibers could be traced to their termination as climbing fibers in sagittal zones of the contralateral cerebellar cortex. Reaching the cerebellum via the restiform body, the labelled olivocerebellar axons entered the deep cerebellar white matter anterior to the cerebellar nuclei. Most of these thicker, nonterminal axons continued dorsally around the nuclei, but some ran through them. Bundles of fibers could be followed into the folial white matter toward their cortical zones of termination. Depending on which part of the olivary complex that was injected with PHA-L, labelled axons were seen to converge on different regions of the cerebellar nuclei, where dense plexuses of thin varicose terminal fibers appeared. Quantitative estimates of the innervation ranged from 1.7 to 4.3 million boutons per mm3 in the fastigial (FN), interposed, and main parts of the lateral cerebellar (LCN) nuclei, whereas the parvicellular portion of LCN demonstrated 15-20 million varicosities per mm3. Frequently, thicker olivocerebellar axons, which seemed directed toward the cerebellar cortex, were seen to send a fine collateral branch toward these areas of nuclear innervation. As controls, PHA-L was injected into the degenerated olivary complex of 3-acetylpyridine-treated rats. Neither cortical climbing fiber terminals nor nerve terminal plexuses in the nuclei appeared in these experiments. In cases with injection sites extending into the reticular formation, substantial mossy fiber labelling was present bilaterally in the cortex, but the cerebellar nuclei were devoid of labelled innervation or demonstrated only a few larger diameter fibers. The projection of the inferior olivary complex to the cerebellar nuclei was strictly topographically organized and agreed in principle with the organization described in the cat by Groenewegen et al. ('79). The caudal medial accessory olive (MAO) projected to FN, the rostral MAO to the posterior interposed nucleus (NIP), the rostral part of the dorsal accessory olive (DAO) to the anterior interposed nucleus (NIA), and the principal olive (PO) to LCN.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-lasting inhibitory action of caerulein on climbing fiber system in the cerebellum of the rat

Caerulein caused a marked decrease in levels of guanosine 3′, 5′-cyclic monophosphate (cGMP) in the cerebellum in rats. This effect was observed to be dose-dependent after the intraperitoneal administration of caerulein for doses over 20 μg/kg and lasted for about 4 hr in doses of 100 μg/kg. However, in vagotomized rats, caerulein failed to alter the level of cGMP in the cerebellum. Caerulein suppressed harmaline-induced increases in cGMP in the cerebellum for more than 30 hr. In contrast, the increases in levels of cGMP in the cerebellum, induced by treatment with methamphetamine, apomorphine and picrotoxin, were not inhibited by pretreatment with caerulein. These results suggest that the peripheral administration of caerulein can inhibit the activity of climbing fibers for a long period of time in the cerebellum of the rat through the stimulation of the abdominal vagus nerves.

Corticotropin-releasing factor in olivocerebellar climbing-fiber system of monkey (Saimiri sciureus and Macaca fascicularis): parasagittal and regional organization visualized by immunohistochemistry

An antiserum directed against the human form of corticotropin-releasing factor (CRF) was utilized for immunohistochemical visualization of the distribution of this peptide in the inferior olivary nucleus and cerebellum of 2 monkey species (Saimiri sciureus, Macaca fascicularis). Colchicine pretreatment was not used. In both species, immunoreactivity was evident in the vast majority of neurons in the inferior olivary nucleus, with perikarya in the medial accessory olive exhibiting especially intense staining. In cerebellum, no labeled perikarya were present, but immunoreactive axons exhibiting the morphological characteristics of climbing fibers and their collaterals were observed in cortical and nuclear structures. In the cortex, most labeled axons were confined to the molecular and Purkinje cell layers. In the sagittal plane, individual axonal arbors originated from thick, isolated axons at the base of the molecular layer and repeatedly ramified as they extended toward the cortical surface. In coronal sections, only thin, paired profiles were present. Labeled processes also formed efflorescences in the granular layer of cortex and were evident as highly arborized axons in cerebellar nuclei. In each of these instances, the labeled elements resembled climbing fibers or their collaterals as visualized by other methods. Other labeled processes in the granular layer exhibited the morphological characteristics of mossy fiber axons. Immunoreactive, climbing-fiber-like axons were present in the molecular layer throughout the major regions of cerebellar cortex. However, the most intensely labeled of these axons were strikingly clustered within particular regions and parasagittal domains. In the vermis and intermediate zone, intensely labeled axons were present only within parasagittal zones similar in location to those defined by climbing fiber innervation from the medial accessory olive. Intensely labeled axons were also densely but uniformly distributed within the uvula, the medial region of the dorsal paraflocculus, and the dorsal region of the pyramis, areas that receive their climbing fiber input primarily from the medial accessory olive. Labeled fibers were much less dense and were not clustered in the lateral hemispheres. The present observation of CRF-like immunoreactivity in the monkey olivocerebellar pathway is compatible with the previous observation of CRF mRNA within olivary neurons of rat, baboon, and human (Young et al., 1986) and with recent immunohistochemical findings in rat (Sakanaka et al., 1987; Palkovits et al., 1987), cat (Cummings et al., 1988; Kitahama et al., 1988), sheep (Cummings et al., 1988), and human (Powers et al., 1987).(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in the responses of cerebellar nuclear neurons associated with the climbing fiber response of Purkinje cells

Previous studies demonstrated that climbing fiber activity produces a short-term increase in the responsiveness of Purkinje cells to mossy fiber inputs. This led to the hypothesis that there are concomitant alterations in the discharge of cerebellar nuclear neurons. This series of experiments was initiated to test this hypothesis in simultaneously recorded Purkinje cell-nuclear cell pairs in related regions of the cerebellar cortex and nuclei. In decerebrate cats 50 pairs of Purkinje cells and nuclear neurons were identified and simultaneously recorded during spontaneous activity and during peripheral inputs. Auto-correlograms of nuclear cell activity and cross-correlograms of the simple spike and nuclear cell activity triggered on the occurrence of spontaneous complex spikes demonstrated little correlation between these events and the discharge of nuclear neurons. To examine the effect of evoked climbing fiber inputs on the Purkinje cell simple spike and nuclear cell responses, square wave mechanical stimuli which modulated the discharge of both cells of a pair were applied to the forepaw. A separation technique was used to construct one histogram illustrating the responses of the nuclear neuron and Purkinje cell in trials in which the peripheral stimulus evoked a climbing fiber input to the Purkinje cell and another histogram showing their responses in trials in which no climbing fiber input was activated. Using this separation technique it was shown that the amplitude of most Purkinje cell responses increased by 120–1200% in trials in which climbing fiber inputs were activated. The response amplitude of 68% of the nuclear cells was modified for these pairs. Most changes in nuclear cell responses were increases ranging from 120–220%. These changes were felt to reflect the action of many Purkinje cells converging on the isolated nuclear neuron. The modulation of the nuclear neuron was not due only to the effect of the related Purkinje cell, since the gain change of the Purkinje cell and nuclear cell of each pair was not correlated ( r = 0.01). The discussion of these findings emphasizes that the increased responses of the nuclear cell are most likely produced by the intracortical action of the climbing fiber system on the responsiveness of Purkinje cells to mossy fiber inputs. Climbing fiber collateral input to nuclear neurons also may contribute to the changes in the nuclear cell responses observed in these experiments.

Corticotropin-releasing factor as a transmitter in the human olivocerebellar pathway

This study demonstrates that the neuropeptide, corticotropin-releasing factor (CRF), is present in neurons of the human inferior olivary complex (IOC). The medulla (including the inferior olive) and the anterior vermis of the cerebellum of 6 human controls obtained at autopsy were immunostained with an antibody directed against CRF. CRF receptors in cerebellum were localized with labeled CRF using in vitro receptor autoradiography. The great majority of neurons in all divisions of the IOC expressed CRF immunoreactivity, and CRF-immunoreactive fibers were demonstrated in the hilus of the olive and in the molecular layer of the cerebellum, where they closely resembled climbing fibers as visualized with other methods. CRF receptors were enriched in the cerebellum, with the highest density in inner portions of the molecular layer. These findings in human brain, consistent with studies in tissues from rat, cat, and monkey, demonstrate that CRF may be a peptidergic transmitter in the IOC climbing fiber system and that CRF receptors are expressed by cellular targets in the cerebellum.

Relationship of parasagittal bands of acetylcholinesterase activity to the climbing fiber representation

The organization of the somatosensory representation by the climbing fiber system was correlated to parasagittal zones in the vermis, which were demarcated by the parasagittal banding pattern of acetylcholinesterase (AChE) activity. Extracellular recordings were made of climbing fiber responses that were elicited by tactile stimulation in anesthetized cats. After the climbing fiber representation was mapped physiologically, the cerebellum was histologically processed for AChE activity. The lateral edge of the lateral AChE banding coincided with the junction between a medial vermis (zones A and X) where 82% of the units were unresponsive and the lateral vermis (zone B) where 72% of the climbing fiber responses represented areas of the body surface.

Somatosensory representation of the cerebellar climbing fiber system in the rat

The climbing fiber responses of 542 Purkinje cell were isolated in the vermal and intermediate zones of lobules II to VI of the rat cerebellum. Mechanical stimulation successfully elicited 53% of the isolated climbing fiber responses, whereas the remaining units were unresponsive to any stimulation employed. Of the units elicited by the stimulation, 34% required cutaneous and 66% required deep stimulation. Some proportion of the representation of each body region required either cutaneous or deep stimulation. The hindlimb had the largest representation and accounted for 55% (160/288) of the units. In contrast, the forelimb was only represented by 10% of the units, the tail by 16%, the face by 11% and the remaining 6% of the units by surface regions of the spine, chest and abdomen. On the basis of their proportional representation of body regions, 3 different cortical areas were distinguished: (1) a medial vermis, which consisted predominantly of unresponsive units; (2) a lateral vermis, which included representations of the extremities, trunk and tail; and (3) the intermediate zone, where the only representation of the face was evident. Within each area, the representations formed a disjunctive pattern of irregularly shaped patches and areas of overlap. In comparison with the climbing fiber organization of the cat, the medial vermal unresponsive zone and the patch-like representations of various body surfaces in the rat were similar to the cat, but the proportional representation of various body surfaces and effective stimulus modality were different, which may reflect morphological and behavioral differences between the species.

Somatosensory representation of the climbing fiber system in the rostral intermediate cerebellum.

The fine grain organization of the climbing fiber (CF) representation for the intermediate cortex of lobules III, IV, and Va was examined. Data were obtained from cats anesthetized with sodium pentobarbital. Through extracellular recording techniques, CF responses were identified in 814 Purkinje cells; 74% were elicited by mechanical stimulation of various body surfaces. Of the CF responses elicited by stimulation, 60% involved the ipsilateral hindlimb, 36% represented parts of the forelimb, and only 4% represented areas of the face, tail, or abdomen. Hindlimb representation predominated in lobules III and IV, and forelimb representation was mainly confined to lobule Va. No distinct parasagittal zones that involved all three lobules were identified. In general, the organization for most sublobules could be best described as a mixture of patches of forelimb or hindlimb representations. Within the patches there was considerable diversity of receptive field types, particularly for the extremities. The receptive fields involving the distal phalanges were generally smaller than those for the proximal areas, but a range in field sizes was evident for both distal and proximal regions. More than half of either the forelimb or the hindlimb representation was limited to the distal paw areas; the two middle toes received the most frequent representation. Representations of the proximal limb areas were generally centered around either the wrist or the heel, or around the elbow or knee, but many of these receptive fields also extended to the phalanges. The multiple representation of various areas of forelimb and hindlimb throughout the rostral intermediate cortex was consistent with the type of organization that had been identified in other regions of the anterior lobe, although each cortical area contained a unique proportional CF representation of various body areas.

Selective retrograde labelling of the rat olivocerebellar climbing fiber system with d-[ 3h]aspartate

Selective retrograde labelling of the olivocerebellar climbing fiber system with d-[ 3H]aspartate has been observed in the rat, and the results have implications for the identification of a transmitter candidate as well as the neuroanatomical understanding of these cerebellar afferents. Microinjections of d-[ 3H]aspartate (50 nl, ca 10 -2 M) were made into various parts of cerebellar cortex. Survival times were 6,12 or 24 h. Pronounced diffusion of the tracer resulted in large injection sites. Within the zone of injection, glial elements were labelled over background. Most granule cells exposed to the tracer were unlabelled; the small numbers demonstrating labelling were believed to have been injured by the micropipette penetration. Beneath injection sites, large numbers of well-labelled nerve fibers appeared in the white matter and could be followed through the brainstem to the contralateral inferior olive, where labelled perikarya were found. After the inferior olivary neurons had been effectively destroyed with 3-acetylpyridine, evidence of cerebellar afferent labelling with d-[ 3H]aspartate was missing. Retrograde labelling of the olivocerebellar system was also observed after superfusion of the verrais with d-[ 3H] aspartate at concentrations in the range of K m for high affinity uptake (10 -5 or 10 -4 M, for 2 h). Mossy fiber or monoaminergic afferents to the cerebellum were never labelled with d-[ 3H]aspartate. The distribution of labelled cells in the olivary subnuclei after injections in different cerebellar areas was in line with the olivocerebellar organization previously described in the cat. Moreover, it was demonstrated that fibers from the different subnuclei follow different routes through the brainstem towards the cerebellum. Labelling of climbing fiber collaterals in uninjected parts of cerebellum indicated that some of the retrogradely migrating d-[ 3H]aspartate was directed in anterograde direction at axonal branching points. Collaterals were demonstrated in all deep cerebellar and Deiters' nuclei, and the results of intranuclear injections suggested that virtually every olivary neuron sends collaterals to these nuclei. Intracortical collaterals were organized in sagittal zones. Midline injections into the anterior lobe and VI lobule labelled collaterals in several zones of the posterior lobe spinal area and uninjected parts of the anterior lobe vermis. Hemispheral injection into copula pyramidis labelled collaterals in two prominent bundles in the anterior lobe. Injection into lobulus paramedianus and crus II gave massive collateral labelling in lobulus simplex, crus I, and laterally in lobuli IV–V, while fewer fibers ran to paraflocculus. Injection into lobulus simplex labelled collaterals in two or three zones of crus II and lobulus paramedianus. Injection into paraflocculus labelled collaterals in crus I, crus II and lobulus paramedianus. These results suggest that all olivocerebellar neurons share a selective affinity for d-[ 3H]aspartate, which is in line with proposals that aspartate may be their transmitter. Further, the study demonstrated the organization of the olivocerebellar pathway through the brainstem, and the complex pattern of climbing fiber collateralization to deep cerebellar nuclei and different regions of cerebellar cortex.

Somatotopy of climbing fiber branching to the cerebellar cortex in cat

The study was aimed at determining the distribution and incidence of the inferior olive axonal branching as related to the somatotopic organization of the climbing fiber system in cat. Multiple fluorescent tracing was used. In a first set of experiments, spectrally different fluorescent tracers were injected into somatotopically defined areas of the anterior lobe-pars intermedia and of the paramedian lobule. Retrogradely labeled cells were found to be localized in well-segregated face-forelimb or hindlimb olivary domains, within the various subdivisions. A large and consistent number of the olive cells were found to send axonal branches to face-forelimb or hindlimb regions of the anterior lobe-pars intermedia and of the paramedian lobule. It was also found that inferior olive branching is restricted to somatotopically corresponding areas of the two lobes. In a second set of experiments the same technique was used to check whether the inferior olive neurons which project to the forelimb areas of the anterior lobe-pars intermedia and the paramedian lobule also send collaterals to the face-forelimb areas of crus II (medial crus II). The data show that different sets of neurons projecting either to the face-forelimb areas of crus II and anterior lobe-pars intermedia or of crus II and paramedian lobule coexist within the face-forelimb related olivary domains with the set of neurons projecting to the face-forelimb areas of the anterior lobe-pars intermedia and paramedian lobule. Neurons branching to the 3 cerebellar regions were observed only occasionally. Therefore, at least for the face-forelimb-related cerebellar areas, the climbing fiber branching can be said to originate in sets of inferior olive neurons that connect different pairs of somatotopically homologous cerebellar cortical areas. The branching pattern is present in all the cortical zones studied, namely C1-C3, C2, D1 and D2, and appears to be a general feature of the olivocerebellar system.

Locus coeruleus stimulation potentiates Purkinje cell responses to afferent input: The climbing fiber system

In cerebellum, the evoked responses of the Purkinje cell to both excitatory and inhibitory afferent input have previously been shown to be enhanced by local iontophoresis of norepinephrine (NE). The influence of locus coeruleus (LC) conditioning stimulation on Purkinje cell responses to climbing fiber input was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar potentiative effects. Stimulation of LC, at intensities which by themselves were subthreshold for directly affecting background activity, markedly enhanced complex spike excitation of Purkinje cells elicited by activation of climbing fiber inputs from sensorimotor cortex. Depressant responses observed after complex spike excitation were also augmented by the LC conditioning. Iontophoretic application of sotalol, a specific β-adrenergic receptor blocker, reversibly antagonized this facilitation of climbing fiber-evoked responses. In addition, the potentiative effects of LC stimulation were not observed after destruction of NE-containing axons and terminals in cerebellum by 6-OHDA. These results suggest that noradrenergic input from the LC can enhance the efficacy of climbing fiber synaptic action on the Purkinje cell, and are thus consistent with the hypothesis of a ‘modulatory’ role rather than a specific information transfer function for NE in cerebellum.

Neurophysiological and behavioral maturation of cerebellar function studied with tremorogenic drugs

Harmaline acts on the olivo-cerebello-reticular system to cause tremor. In infant rats, this system is immature. Harmaline-induced tremor develops during the second week of life, at approximately the same age as the climbing fiber synapses on the Purkinje cells assume a morphologically mature form. This suggests that the maturation of the climbing fiber synapses may be a critical event in the functional maturation of the cerebellum. To test this, the effects of harmaline on the behavior and neurophysiology of developing infant rats were studied. A method of probit analysis was developed to compare statistically the age of development of different responses in the rat. Probit analysis showed that neonatal rats developed the ability to tremor in response to harmaline at 9.4 ± 1.8 (mean ± SD) days of age. Using a method for recording from infant rats, the harmaline-induced bursting pattern of cell firing recorded from the cerebellum and inferior olive developed at 9.7 ± 3.8 and 11.0 ± 1.5 days, respectively. There was no statistically significant difference between these three ages. This measurement of the development of harmaline responses represents an accurate timing of developmental events and the direct statistical comparison of the age of occurrence of these events. This study provides a direct statistical comparison of cerebellar development as determined electrophysiologically and behaviorally. The use of harmaline allowed the study of the climbing fiber system specifically, and provided electro-physiological data on inferior olive development. The data indicate that the inferior olive cell becomes functionally mature at 10 days and this development is the critical event in the emergence of harmaline-induced tremor.

Information about peripheral events conveyed to the cerebellum via the climbing fiber system in the decerebrate cat

Discharges of Purkinje cells (PCs) with simple (SS) and complex spikes (CS) in the c1-zone of lobule Vc of the anterior lobe of the cerebellar cortex were analyzed in the decerebrate cat during a passive movement of the cat forepaw. The CS of the PC responded differentially and/or proportionally to the position of the extremity, amplitude of the movement, velocity and acceleration. Inphase and outphase responses of the climbing fiber (CF) system to sinusoidal movements could depend on the position of the extremity within the operational range. From these results we deduce that peripheral events can be signalled by the CF system. The possible function of the interaction between the two inputs at the PC level is discussed.

The effect of lesions of the dorsal cap of the inferior olive on the vestibulo-ocular and optikinetic systems of the cat

The gain (eye velocity/head velocity) of the vestibulo-ocular reflex (VOR) of cats was measured in the dark and light for sinusoidal head oscillations at 0.05 and 1.2 Hz with peak velocity of about 30 deg/sec. Animals wore visual reversing prisms chronically and were also subjected to forced oscillation in the light at 0.05 Hz for 2 h per day. Such experience produced adaptive reduction in VOR gain in the dark from 0.85 to 0.10 within about 4 days; qualitatively similar effects were observed at 1.2 Hz. In 4 cats, the dorsal cap of the inferior olive was located electrophysiologically by its responses to visual motion, and bilateral electrolytic lesions were made in or near this structure. The location of lesions was subsequently identified by histology. After lesions, 3 cats were unable to make adaptive changes in VOR gain when confronted with the same reversing prism paradigm; the fourth exhibited appreciable retardation of adaptation. These results imply that the dorsal cap is essential for plastic adaptation of the VOR. However, all cats retained the ability to use reversed vision to reduce VOR gain in the light after lesions. Optokinetic nystagmus (OKN) and optokinetic after nystagmus (OKAN) were measured in a striped optokinetic drum, before and after dorsal cap lesions, at drum velocities of 20 and 40 deg/sec. Lesions of the dorsal cap in 4 cats did not impair either OKN or OKAN. This result indicates that the climbing fiber system reaching the flocculus from the inferior olive is not essential for such optokinetic movements.

Termination in overlapping sagittal zones in cerebellar anterior lobe of mossy and climbing fiber paths activated from dorsal funiculus.

The termination patterns in the cerebellar anterior lobe of one mossy fiber path, the exteroceptive component of the cuneocerebellar tract (E-CCT), and one climbing fiber system, the dorsal spino-olivocerebellar paths (DF-SOCPs), which both relay in the main cuneate nucleus, were compared in the cat. The E-CCT terminates in the ipsilateral half of the anterior lobe in five sagittal zones which overlap five of the eight zones activated from the DF-SOCPs. In at least one zone the E-CCT projection has a somatotopical organization which is similar to and overlaps that of the DF-SOCP.

Brain modeling by tensor network theory and computer simulation. The cerebellum: Distributed processor for predictive coordination

A fundamental problem regarding the functional interpretation of neural networks in the central nervous system is that of establishing the principles of their parallel, distributed organization. Available morphological and physiological knowledge concerning the cerebellum suggests that the central nervous system may use organizational principles other than the traditionally assumed ‘random connectivity’, ‘reflex loops’ or ‘redundancy’. We propose formally, and demonstrate by computer modeling, that the firing frequencies of individual cells over a cerebellar cortical area may be interpreted as a spatially distributed, finite, series expansion of a time function, which is reconstructed, by summation, in the nucleus where the cortical cells project. Thus, for example, the firing of Purkinje cells, when considered as representing a Taylor expansion, yield a prediction in the cerebellar nuclei of the frequency-time function of the input arriving at the cortex. This ‘lookahead’ (Δ) is an emergent property of the inherently parallel, distributed network. In order to analyze how a Taylor expansion-like process is used by the cerebellum on a system level, the linear algebraic matrix- and vector-representation of a distributed network was generalized in such a way as to regard the neuronal networks as tensors. Thus, the brain is envisioned as a set of tensorial systems which communicate with each other through vectorial channels (the pathways). These pathways carry multidimensional frequency vectors which are transformed by the tensors. In these terms the function of a particular subsystem of the central nervous system, in the present case the cerebellum, is represented in a multidimensional space. The frequency-hyperspace is characterized by the matrix of the cerebellar tensor which specifies a curved set of trajectories: a cerebellar vector field. Dynamic posture and balance are interpreted as displacement or stabilization of the functional status vector of the motor system along these curved trajectories. Cerebellar coordination of ballistic movements can be described as guiding the movement onto the ‘wired in’ trajectories of the vector field, by virtue of the coordination and inhibition vectors provided by the cerebellum. A proposal is also introduced that the climbing fiber system operates by momentary perturbations of the vector field, leading to deformations of the trajectories of the cerebellar frequency hyperspace. To bridge the gap between an attempt to treat parallel, distributed, neuronal networks, such as the cerebellum, as geometrical objects (leading, at the first approximation, to a linear mathematical formulation) and the simultaneous task of incorporating and interpreting experimental data, computer simulation methods are required. This combined approach of mathematical treatment (which provides an abstract language) and computer simulation (which, by accommodating data into the model, explores the significance of deviations from linear character) appears at present to be the most adequate technique for dealing with central nervous system function.

Discharge patterns of Purkinje cells activated through the climbing fiber system by stimulation of somatic and visceral afferents.

Extracellular recordings were obtained from single Purkinje cells (PC) in the intermediate part of the lobule V and VI of the cerebellar cortex in cats anaesthetized with Nembutal. A number of PC responded with a "complex spike" (CS) to stimulation of both the superficial radial nerve (SRN) and the vagus nerve (VN). By suppressing the transmission of mossy fiber (MF) inputs through manipulation of the level of anaesthesia, attention was paid to the "simple spike" (SS) activity after the CS. Modality-specific differences were found in the length of the post-CS pause, the presence of a post-pause rebound, the effect of pre-CS SS firing rate on pause duration and in the frequency and regularity of post-pause SS discharge. We concluded that these differences arouse from the location of the PC within the climbing fiber (CF) sagittal strip and from the differential activation of the inhibitory interneurons. We propose that modification of SS activity following a CS represents a possible means of information transmission by the CF system.

Visual and visual-vestibular responses of frog cerebellar neurons

Micropipette recordings were obtained from single neurons of the frog cerebellum to monocular and binocular visual stimuli. 64% of the visually activated cerebellar neurons could be identified as Purkinje cells. Two major groups of cerebellar visual neurons could be distinguished: The neurons of the first group have restricted receptive fields within the visual field of one or both eyes and respond to diffuse illumination or to small contrast stimuli moving through the receptive field. The neurons of the second group have no restricted receptive fields and respond best to a moving patterned surround, stimulating one or both eyes. Among these neurons four classes could be distinguished by binocular surround stimulation: Neurons activated by horizontal movement to the right (C1 neurons), neurons activated by movement to the left (C2 neurons), neurons activated by movement in both directions (C3 neurons) and neurons which are inhibited by movement in both directions (C4 neurons). The contribution of each eye to the binocular response revealed that the signals from both retinae interact either in a Homodirectional or a Heterodirectional manner. Stimulation of the receptors in the horizontal semicircular canal (horizontal turning movement) leads to a change in the activity of cerebellar visual neurons. Depending on the directionality of the neurons, an enhancement or a reduction in the neuronal activity can be achieved by combining visual and vestibular stimulation. Electrical optic nerve stimulation revealed two latency ranges for the activation elicited by the mossy fiber as well as by the climbing fiber system.

The indolaminergic innervation of the inferior olive. 2. Relation to harmaline induced tremor

The possible involvement of serotoninergic mechanisms in the induction of harmaline generated tremor in the inferior olive has been investigated electrophysiologically in the cat and rat. Mass recordings of Purkinje cell activity in the cat showed that harmaline induces strong, synchronous and rhythmic activity in those parts of the climbing fibre system originating in the caudal part of the medial accessory olive and the caudolateral parts of the dorsal accessory nucleus. These are the areas of the cat olive shown to receive a dense serotoninergic innervation. In the rat, the selective removal of the serotoninergic innervation — produced by an intraventricular injection of 5,6-dihydroxytryptamine, or 5,7-dihydroxytryptamine in combination with desipramine — caused a significant attenuation of both the tremor and the climbing fibre activity induced by an intravenous harmaline injection. In the 5,6-dihydroxytryptamine-treated animals the reappearance of the harmaline tremor seemed to parallel the regrowth of new serotoninergic axon sprouts in the inferior olive. On the basis of the present results it is proposed that the serotoninergic afferents to the accessory olivary nuclei are of critical importance for the tremor induction of harmaline in the inferior olive. It is suggested that harmaline, rather than acting directly on the olivary neurones, exerts its effect through an interference with a serotoninergic (possibly inhibitory) innervation of these cells.

The climbing fiber system in the Weaver mutant

The climbing fiber system in the Weaver mutant