Demonstration of a somatotopical pattern in the cortico-olivary projection in the cat an experimental-anatomical study

Summary Following small lesions of the first sensorimotor (MSI) and second somatosensory (SII) cortical areas the ensuing degeneration in the inferior olives was studied with the Nauta method in 14 cats.No convincing signs of degeneration were found in the olives in cases with lesions restricted to the first and second somatosensory areas (SI and SII). Following lesions of the primary motor cortex (anterior sigmoid gyrus and rostral part of the coronal gyrus) degeneration was consistently found in the olive of both sides. The contralateral projection is somewhat more abundant than the ipsilateral, but both are modest.Degeneration is restricted to certain parts of the olivary complex (see Fig. 11). Lesions restricted to different somatotopical subdivisions of the primary motor cortex give rise to degeneration distributed in a somatotopical pattern in certain areas of the medial and dorsal accessory olives and the rostral part of the ventral lamella. Somatotopical patterns could not be established in the smaller projections to some other minor olivary regions.When the findings are correlated with the pattern of the olivocerebellar projection it can be concluded that there is a somatotopically organized direct corticoolivo-cerebellar pathway to the intermediate part of the anterior lobe, the posterior vermis and the crus II.Attempts to correlate the findings with physiological observations are difficult. It appears that the current view that climbing fibres arise only in the olive may need revision. The role of the pontine nuclei in mediating somatotopically localized cerebellocerebellar impulses appears to have been underestimated.Working in the Anatomical Institute, University of Oslo, Norway, with leave of absence from the Anatomical Institute, University of Porto, Portugal, under a fellowship from the Calouste Gulbenkian Foundation, Lisbon, Portugal.     

Ultrastructure of the gracile nucleus projection to the dorsal accessory subdivision of the cat inferior olive

Summary This study examined the termination pattern within the dorsal accessory subdivision of the cat inferior olive of axons arising from the gracile nucleus. The gracile terminals were labeled by anterograde transport of wheat germ agglutinin complexed to horseradish peroxidase and visualized with tetramethyl benzidine. Gracile terminals were found to contain round synaptic vesicles and form asymmetric synaptic contacts. Of particular interest was the finding that gracile axons, like axons from the spinal cord, terminate primarily outside of synaptic glomeruli. Yet most of the gracile terminals did not synapse on isolated dendritic elements. Rather, the majority contacted distal dendrites which directly contacted other dendritic elements, forming simple complexes termed dendritic thickets. Typically the dendritic thickets were composed of two or three dendrites that received input from more than one round vesicle-containing synaptic terminal. Only one terminal per thicket was labeled by injections in the gracile nucleus. This clustering of pre-and postsynaptic elements within the thickets provides opportunities for many of the same interactions allowed by synaptic glomeruli, in particular divergence and convergence of information.     

A rubro-olivary pathway I. identification of a descending system for control of the dynamic sensitivity of muscle spindles

Summary In cats anesthetized with halothane the influence of central stimulation upon the dynamic sensitivity of muscle spindles in the flexor digitorum longus muscle was studied. One mesencephalic and one medullary region were found which caused an increase in dynamic spindle sensitivity when stimulated electrically. Histological identification of stimulating points showed these regions to be the caudal pole of the red nucleus and the inferior olivary nucleus respectively. Lesions in the olive decreased rubral effects on the spindles, indicating that the red nucleus and the olive are parts of the same system descending to dynamic fusimotor neurones. Further evidence for this point are given in a following paper (APPELBERG 1967).     

Excitatory inputs to cerebellar dentate nucleus neurons from the cerebral cortex in the cat

Summary 1. In anesthetized cats, we investigated excitatory and inhibitory inputs from the cerebral cortex to dentate nucleus neurons (DNNs) and determined the pathways responsible for mediating these inputs to DNNs. 2. Intracellular recordings were made from 201 DNNs whose locations were histologically determined. These neurons were identified as efferent DNNs by their antidromic responses to stimulation of the contralateral red nucleus (RN). Stimulation of the contralateral pericruciate cortex produced excitatory postsynaptic potentials (EPSPs) followed by long-lasting inhibitory postsynaptic potentials (IPSPs) in DNNs. The most effective stimulating sites for inducing these responses were observed in the medial portion (area 6) and its adjacent middle portion (area 4) of the precruciate gyrus. Convergence of cerebral inputs from area 4 and area 6 to single DNNs was rare. 3. To determine the precerebellar nuclei responsible for mediation of the cerebral inputs to the dentate nucleus (DN), we examined the effects of stimulation of the pontine nucleus (PN), the nucleus reticularis tegmenti pontis (NRTP) and the inferior olive (IO). Systematic mapping was made in the NRTP and the PN to find effective low-threshold stimulating sites for evoking monosynaptic EPSPs in DNNs. Stimulation of either the PN or the NRTP produced monosynaptic EPSPs and polysynaptic IPSPs in DNNs. Using a conditioning-testing paradigm (a conditioning stimulus to the cerebral peduncle (CP) and a test stimulus to the PN or the NRTP) and intracellular recordings from DNNs, we tested cerebral effects on neurons in the PN and the NRTP making a monosynaptic connection with DNNs. Conditioning stimulation of the CP facilitated PN- and NRTP-induced monosynaptic EPSPs in DNNs. This spatial facilitation indicated that the excitatory inputs from the cerebral cortex to DNNs are at least partly relayed via the PN and the NRTP. 4. Stimulation of the contralateral IO produced monosynaptic EPSPs and polysynaptic IPSPs in DNNs. These monosynaptic EPSPs were facilitated by conditioning stimulation of the CP, strongly suggesting that the IO is partly responsible for mediating excitatory inputs from the cerebral cortex to the DN. A comparison was made between the latencies of IO-evoked IPSPs in DNNs and the latencies of IO-evoked complex spikes in Purkinje cells. Such a comparison indicated that the shortest-latency IPSPs evoked from the IO were not mediated via the Purkinje cells and suggested the pathway mediated by inhibitory interneurons in the DN. 5. The functional significance of the excitatory inputs from the PN and the NRTP to the DN is discussed in relation to the motor control mechanisms of the cerebellum.     

The dorsal spino-olivocerebellar system in the cat

Summary The spino-olivocerebellar paths ascending through the dorsal funiculi (DF-SOCPs) were studied by recording climbing fiber field potentials in the cerebellar cortex. Several DF-SOCPs were identified on the basis of their response latencies, peripheral inputs, and projection areas. The projection areas consist of eight sagittal zones on each side of the anterior lobe denoted a, x, b, C₁, c₂, c₃, d₁, and d₂. The a and b zones, which are activated exclusively from hindlimb nerves (Oscarsson, 1969a) were not studied.The shortest response latencies in the x, c₁, c₃ and d₂ zones indicate that these zones are activated by direct paths between the dorsal funiculus nuclei and the inferior olive. These zones also have long latency responses evoked through indirect paths. The direct paths are activated from the flexor reflex afferents and the indirect paths from distal cutaneous afferents. The x zone is activated from forelimb nerves only. The c₁ and c₃ zones and presumably also the d₂ zone are activated from hindlimb and forelimb nerves and have a detailed somatotopical organization.The c₂ and d₁ zones have long latency responses evoked through indirect paths. Both zones are activated from distal cutaneous afferents. The c₂ zone has no distinct somatotopical organization, whereas the d₁ zone has largely separate forelimb and hindlimb areas. In contrast to all other zones, the c₂ zone is activated not only from ipsilateral but also from contralateral nerves.     

The climbing fibers of the cerebellar cortex,their origin and pathways in cat

Summary The sources and pathways of the climbing fibers to the cerebellar posterior vermis were studied with combined electrophysiological and anatomical methods in cats.Recording from identified cerebellar Purkinje cells, monosynaptic climbing fiber (CF) responses have been obtained both for stimulation of the inferior olive (IO) and various parts of the brain stem (BS). CF responses were found to be of three types, IO only, BS only or both IO and BS. However the responses to BS stimulation were very few in number in comparison with IO or IO and BS types of responses. The latencies of the responses were shorter for the BS cases consistent with their distance from the cerebellum.A comparison of latencies and the relative responsiveness of the different area of the brain stem which were studied, indicate that part of the CF ascend through the pontine region and enter the cerebellum by way of the medium and superior peduncles. This finding is confirmed by the results of anatomical studies in which degenerating fibers were found in the molecular layer (using the Nauta technique) after lesion of the brachium pontis but not after lesions of the medial portion of the pons. Similarly, injection of radioactive leucine into the pontine nuclei failed to show any labeled fibers in the molecular layer.Horseradish peroxidase (HRP) was injected into localized regions of the posterior vermis after total bilateral destruction of the inferior peduncles. Large numbers of positive, marked cells were still found in the inferior olive.It is concluded that nearly all, if not all, the climbing fibers originate in the inferior olive and that they ascend to the cerebellum by way of all the peduncles.     

A Rubro-Olivary pathway II. Simultaneous action on dynamic Fusimotor neurones and the activity of the posterior lobe of the cerebellar cortex

Summary In the preceding paper (Appelberg and Molander 1967) the caudal part of the red nucleus and parts of the inferior olivary nucleus were shown to cause increased dynamic sensitivity of muscle spindles when stimulated repetitively. The results to be presented will show that single shock electrical stimulation in the caudal part of the red nucleus evoked a field potential in the inferior olivary nucleus. This response seemed to be monosynaptically evoked and was observed only in parts of the olive where repetitive stimulation caused increased dynamic sensitivity of muscle spindles. Stimulation in the red nucleus as well as single shock stimulation in the actual part of the inferior olive also caused a potential in the vermis of the posterior cerebellar lobe. In conditioning — test experiments with the two stimuli the conditioning shock was seen to cause alternating periods of decreased and increased responsiveness in the pathway concerned. The same type of interaction was seen between two responses caused by double shock stimulation in the red nucleus.It is concluded that information from the caudal part of the red nucleus reaches dynamic fusimotor neurones in the spinal cord via a relay in the inferior olivary nucleus; an additional relay in the pathway is also predicted. The cerebellum seems to receive information about ongoing activity in the pathway but mesencephalic stimulation was seen to cause spindle effects also in decerebellated animals.     

The interrelations between cell groups in the caudal diencephalon of the rat projecting to the striatum and to the medulla oblongata

Summary In order to investigate the topographical relationships between the caudal diencephalic cells of origin of ascending and descending projections in the rat, one fluorescent retrograde tracer was injected into the striatum and another into the medulla oblongata. The medullary injections were mainly centered in the inferior olive. Cells labeled from the striatal injections densely filled the thalamic parafascicular nucleus. Cells labeled from the medullary injections were seen ventrally to the fasciculus retroflexus in the subparafascicular nucleus. The two populations were mixed in a small area at the ventromedial border of the fasciculus retroflexus. No double labeled cells were observed. The present results indicate that caudal diencephalic cells which ascend to the striatum are different from those descending to the medulla oblongata and that they partially overlap.Supported in parts by CNR grants N. 80.00515-04, 81.00283.04     

Quantitative analysis of the distribution of the motor cortex representations of the fore-and hindlimbs in the red nucleus of the cat

A quantitative analysis of the distribution of corticorubral fibers was performed after precise electrolytic lesioning of the lateral and medial margins of the posterior sigmoid gyrus — the motor representations of the fore-and hindlimbs respectively — in cats. The cortical representations of the forelimbs were found to project to the whole of the rostrocaudal extent of the red nucleus (RN). The number of efferent fibers terminating at the rostral margin of the RN was almost twice that terminating in the caudal third of the RN. Efferent fibers of the cortical representation of the hindlimbs did not project to the rostral two thirds of the RN but ended in its caudal third; the number of projecting corticorubral fibers was the same as the number running from the cortical representation of the forepaws to the caudal third of the RN. The significantly (almost double) greater number of fibers running from the cortical representation of the forelimbs in comparison with the number directed from the representation of the hindlimbs found in the present study is probably evidence of the greater functional importance of corticorubral connections in movement reactions performed by the forelimbs. __________ Translated from Morfologiya, Vol. 131, No. 2, pp. 29–31, March–April, 2007.     

Olivary projections to the cerebellar nuclei in the cat

Summary Projections from the inferior olive to the cerebellar nuclei have been studied in the cat using Nauta's silver technique. 1. Numerous degenerating terminals occur after lesions in the inferior olivary complex in the medial nuclei of both sides; the degeneration is considerably less in the subnucl. medialis parvicellularis of both sides. In the interpositus nuclei of both sides degenerating terminals are also abundant, especially in their dorsal and lateral parts. In the lateral nucleus a number of degenerating terminals are seen on both sides restricted to dorsal and lateral parts of the nuclei. Degeneration is scanty in the subnucl. lateralis parvicellularis. 2. Projection of the olivocerebellar fibers to the cerebellar nuclei is always bilateral. The fibers originate in the inferior olive and ascend mainly through the contralateral, however, some also through the ipsilateral restiform body. The olivocerebellar fibers that have crossed in the medulla terminate in the medial and the interpositus nuclei of both sides. It is suggested that the degenerating terminals found in the cerebellar nuclei are derived from collaterals of the olivocerebellar tract fibers.     

Inferior olive excitability after high frequency climbing fibre activation in the cat

Summary 1. Climbing fibre responses (CFRs) were evoked by limb nerve stimulation and recorded from the cerebellar surface in barbiturate anaesthetized cats. Climbing fibres were activated at frequencies of usually 2.5–7.5 Hz for periods of 15–30 s, after which the stimulation frequency was reduced to below 1 Hz. 2. The high-frequency stimulation induced a strong depression of CFR-amplitude, lasting up to 60 s. The magnitude of this depression was dependent on both the frequency and the duration of the high-frequency stimulation. 3. The depression occurred in the c1, c2 and c3 zones of the pars intermedia and in the x zone in the vermis but not in the b zone in the vermis. 4. Recordings of olivary reflex responses demonstrated that the depression occurred in the inferior olive. 5. It is suggested that the inhibition of the inferior olive occurs because the high-frequency stimulation leads to a disinhibition of neurones in the interpositus nucleus which inhibit the olivary neurones.     

The character and influence of the claustral pathway to the striate cortex of the cat

Summary 1. In paralyzed and anaesthetized cats, the pathway running from the claustrum to the striate cortex was characterized from the transynaptic latencies of responses that were initiated by electrical stimulation in the claustrum (CL) and recorded extra-cellularly in single striate neurons. A second stimulating electrode (OR₁) in the primary visual pathway provided information on the input coming to the recorded cell from the lateral geniculate nucleus. 2. An analysis of the classified striate neurons receiving a claustral drive revealed that 68% were C cells and 26% were S cells. For the C cells, 81% had CL latencies of less than 2.5 ms (mean = 1.8 ms) and the potential to receive a direct drive from a fast conducting input; the remaining 19% had latencies around 3.0 ms (mean = 3.0 ms), a value consistent with a disynaptic input from the same type of input. 3. From their CL latencies, the S cells also could be subdivided into two subgroups; one, made up of 36% of the sample had CL latencies of less than 2.5 ms (mean = 1.9 ms) and the capacity, like the majority of C cells, to receive a direct, fast-conducting input; the second subgroup, consisting of 74% of the S cells, had CL latencies longer than 3.0 ms (mean = 5.4 ms). 4. The majority of cells with a claustral-drive (85%) were encountered either in laminae 4 or 6. Claustral-driven cells belonging to both S and C catagories were found in the two laminae (4 and 6) and there was no observed predisposition for a particular cell type to cluster in either of these lamina. 5. From a comparison of CL and OR₁ latencies, justified on the grounds of independent stimulation, a strict correlation was found for signal conduction properties in the claustral and LGN pathways running to a given striate neuron. 6. From a quantitative evaluation of receptive field properties the claustral-driven striate neurons were found to resemble cells in the general population. As a group, however, they were distinctive in that both end-zone inhibition and direction selectivity were either weak or absent from the cell's response. This finding held for cells in both the C and the S categories. 7. It is concluded from the high incidence of claustral-driven C cells, that the claustral loop from the striate cortex is involved in an aspect of motion detection.     

The origin of olivary afferents from the central grey and its surroundings in the cat

Summary The olivary afferents from the mesencephalic central grey and its surroundings have been studied in cats in which microinjections of horseradish peroxidase have been made into the inferior olive from a ventral approach. Retrogradely labelled cells are present in the ventral part of the central grey, the nucleus of Darkschewitsch (especially its ventral part), the Edinger-Westphal nucleus, the interstitial nucleus of Cajal and the reticular formation between the red nucleus and the central grey. The projection is ipsilateral and the heaviest contribution of afferents is derived from the interstitial nucleus of Cajal. The findings indicate that the afferents from the mesencephalic reticular formation to the inferior olive probably are collaterals of fibres terminating dorsally to the olive or passing to the spinal cord.The observations are discussed and related to previous experimental studies in the cat.     

The pathways responsible for excitation and inhibition of fastigial neurones

Summary A detailed study of the latencies of the excitatory responses of fastigial cells disclosed an unexpected anomaly. Except for infrequent small responses the latency was many milliseconds longer than would be expected for excitation by axon collaterals of the fast spino-cerebellar pathways. There were many examples in which inhibition had an earlier onset than excitation; nevertheless the inhibitory latency was not so brief as to preclude its production by Purkyn cell discharge in response to the fast spino-cerebellar pathways. Histograms have been constructed for the latencies of the excitation and inhibition evoked in fastigial cells by four kinds of inputs: nerve volleys from forelimb and hindlimb; pad taps from forelimb and hindlimb.Electrical stimulation of the lateral reticular nucleus on the same side very effectively excited fastigial cells, usually with the latency expected for monosynaptic excitation. It was therefore postulated that with forelimb and hindlimb stimulation the dominant mode of excitation of fastigial cells was by excitatory collaterals from the spino-reticulo-cerebellar pathway. Stimulation of the contralateral inferior olive also was effective in evoking a short latency excitation of fastigial cells. It was therefore assumed that collaterals from the spino-olivo-cerebellar pathway provide an additional excitatory input to fastigial cells.A diagram was constructed in space-time coordinates graphically expressing the timing of the various excitatory and inhibitory pathways by which a hindlimb nerve stimulus acts on fastigial cells. An interesting design feature is thereby disclosed, namely that the dominant excitatory input to the fastigial cells via the slower spino-cerebellar paths is virtually synchronous with the inhibitory input from Purkyn cells discharging in response to the fast spino-cerebellar input. It is pointed out that the temporal pattern gives optimal conditions for the computer-like operation of the fastigial nucleus.     

Synaptic responses of neurons in the parietal associative cortex of the cat to stimulation of the red nucleus

Acute experiments on anesthetized and immobilized cats using intracellular recording were used to study the responses of neurons in the parietal associative cortex to stimulation of the red nucleus. Efferent neurons of the parietal cortex were identified by antidromal activation on stimulation of the intrinsic nuclei of the pons and motor cortex. Oligo- and polysynaptic EPSP in response to stimulation of the red nucleus were seen. The results are discussed in the light of the morphological organization of the rubrothalamic and cerebellothalamocortical tracts. Laboratory for Central Nervous System Physiology (Director V. V. Fanardzhyan), L. A. Orbel' Institute of Physiology, Armenian National Academy of Sciences, Erevan. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 81, No. 12, pp. 64–69, December, 1995.     

Neuronal analysis of skin sensitivity representation in the red nucleus of the alert cat

Responses of the cat's red nucleus to skin stimulation were studied in a chronic experiment by means of the microelectrode technique. The majority of red nucleus neurons had wide receptive fields in which there were areas causing the most intensive and stable activation of the corresponding neurons. A somatotopic principle of skin sensitivity representation in the red nucleus is revealed. After destruction of the cerebellar nuclei and sensorimotor cortex the background activity of red nucleus neurons was reduced, the responses to skin stimulation changed, the peripheral receptive fields got narrower and rearranged. Even so the somatotopic character of skin sensitivity representation in the red nucleus was preserved.     

Electrophysiological analysis of efferent neurons of cat associative parietal cortex

We have studied in acute experiments the neurons of the associative parietal cortex in the cat, using the microelectrode take-off technique. We identified the efferent neurons sending axons to the sensomotor cortex, the red nucleus, and the pontine nuclei by antidromic stimulation. We investigated the collateral branching of axons of neurons projected simultaneously into two of the formations mentioned, using the impulse collision technique. We studied the characteristics of the spatial distribution of efferent neurons in the parietal cortex.Translated from Fiziologicheskii Zhurnal SSSR imeni I. M. Sechenova, Vol. 72, No. 7, pp. 865–873, July, 1986.     

Synaptic organization of the cerebello-thalamo-cerebral pathway in the cat. II. Input-output organization of single thalamocortical neurons in the ventrolateral thalamus

Input-output neural organization of single thalamocortical (T-C) neurons in the ventrolateral nucleus (VL) of the thalamus was investigated using an intracellular recording technique in the anesthetized cat. Stimulation of the dentate (DN) and the interpositus (IN) nuclei produced monosynaptic unitary EPSPs of large amplitude in T-C neurons projecting to the motor cortex or area 6 over the entire mediolateral region of VL. The thalamic projections from DN and IN are very wide and there is a considerable overlap between the dentate and the interpositus projection areas in VL. And in this overlapping area, a considerable number of T-C neurons (50%) receive inputs from both DN and IN. More than 40% of T-C neurons were antidromically activated from widely separated electrodes in the motor cortex, indicating that the cortical arbolization of single T-C neurons is very wide and the number of these neurons with widely divergent projections is considerably large.     

Evidence for a GABA-mediated cerebellar inhibition of the inferior olive in the cat

Summary 1. Climbing fibres were activated by peripheral nerve stimulation at high frequencies (>3 Hz) for 15–25 s and then at 0.9 Hz for about 1 min. The high frequency activation induced a post-conditioning inhibition, lasting up to about 1 min, of climbing fibre responses recorded from the cerebellar surface. 2. Electrolytic lesions were made in the superior cerebellar peduncle (brachium conjunctivum). After the lesion, the post-conditioning inhibition was completely eliminated. 3. Injections of the GABA-receptor blocker bicuculline methiodide into the inferior olive reversibly blocked the post-conditioning inhibition. 4. The results support the hypothesis proposed by Andersson and Hesslow (1987a), that post-conditioning inhibition is mediated by a GABA-ergic interposito-olivary pathway.