Compensatory motor function of the somatosensory cortex for dysfunction of the motor cortex following cerebellar hemispherectomy in the monkey

Summary Electrical activities of the motor and somatosensory cortices preceding visually-initiated hand movements were recorded with electrodes chronically implanted on the surface and at 2.5–3.0 mm depth in the cortex of monkeys, and changes in field potentials in these cortices after cerebellar hemispherectomy were observed for many weeks. As previously reported, a unilateral cerebellar hemispherectomy including the lateral and interpositus nuclei eliminates the cerebellar-mediated superficial thalamo-cortical (T-C) responses recorded in the forelimb motor cortex contralateral to the hemispherectomy. These T-C responses normally precede the hand movement, and the operation results in the delay of movement initiation. The electrodes in the forelimb area of the contralateral primary somatosensory cortex showed an enhancement of superficial T-C responses of the somatosensory cortex for 30–40 days after the operation. The enhanced potentials preceded the delayed movement as do the cerebellar-mediated superficial T-C responses of the motor cortex in normal situations. Local cooling of the somatosensory cortex following the cerebellar hemispherectomy disturbed the reaction time movement for a few weeks after the operation. This effect was rarely encountered in normal monkeys. The present study suggests the compensatory motor function of the somatosensory cortex for the dysfunction of the motor cortex in early weeks after cerebellar hemispherectomy.Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan     

Thalamo-cortical projections for recruiting responses and spindling-like responses in the parietal cortex

1. The thalamic neurones sending their axons to the parietal association cortex (middle suprasylvian gyrus) and receiving monosynaptic excitation from the cerebellar (interpositus or lateral) nucleus were recorded with microelectrodes extracellularly and intracellularly around the anterior ventral (VA) nucleus of the thalamus in cats. Such thalamic neurones are known to carry exclusively the impulses responsible for superficial thalamo-cortical (T-C) responses in the parietal cortex, being called superficial T-C neurones (see Sasaki et al., 1972a, b). 2. Repetitive (6--9/sec) stimulation of the centrum medianum-parafascicular complex (CM) or the intralaminar nuclei (IL) of the thalamus elicited grouped spike discharges of the neurone in synchronization with the recruiting responses in the parietal cortex. The grouped discharges usually preceded the respective cortical responses by several milliseconds. Numbers of the spikes in the grouped discharges increased and decreased as the recruiting responses waxed and waned on the repetitive stimulation. 3. The superficial T-C neurones also showed similar grouped discharges in synchronization with spindling-like, surface-negative cortical responses which occurred spontaneously or were evoked by single thalamic stimulation. 4. It was concluded that the superficial T-C neurons can convey impulses for recruiting responses and spindling-like responses from the thalamus directly to the cerebral cortex. They are supposed to constitute the final T-C pathway of the neuronal circuits of the recruiting system, i.e., non-specific T-C projection system.     

Cortical field potentials preceding visually initiated hand movements and cerebellar actions in the monkey

Summary Cortical field potentials preceding hand movements initiated by a visual stimulus were recorded with chronically implanted electrodes in premotor, motor and somatosensory cortices of monkeys, and the influences of cerebellar hemispherectomy on cortical potentials as well as reaction time of movements were examined.As reported previously, early surface-positive, depth-negative (2.5–3 mm depth from the cortical surface) premovement potentials emerged at about 40 ms latency after onset of the light stimulus bilaterally in premotor and forelimb motor areas. Early potentials in the forelimb motor area contralateral to the moving hand were followed at about 120 ms latency by surface-negative, depth-positive late premovement potentials which are considered to be mainly composed of superficial thalamo-cortical (T-C) responses.Unilateral hemispherectomy of the cerebellum contralateral to the motor area immediately eliminated the surface-negative, depth-positive potentials. Reaction time from onset of the light stimulus to the hand movement was prolonged by 90–250 ms after cerebellar hemispherectomy. If the dentate and interpositus nuclei were also lesioned, disappearance of the late potentials and delay of the movement continued for many months. However, if the interpositus was spared, there was earlier recovery of reaction time with simultaneous reappearance of the late premovement potentials in the motor cortex.The conclusion is drawn that the cerebellar hemisphere (neocerebellum) activates the motor cortex via superficial T-C projections and participates directly in the initiation of reaction movements in response to an external stimulus.Supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan     

Projection of the cerebellar dentate nucleus onto the frontal association cortex in monkeys

Summary Stimulation of the cerebellar dentate nucleus in monkeys elicited responses in the frontal association cortex (area 9) on the contralateral side to the stimulation, in addition to those in the motor (area 4) and premotor (area 6) cortices which were reported previously.The responses in the frontal association cortex were characterized by surface positive-deep negative field potentials in the cortex. They contrasted with surface negative-deep positive potentials in the motor and premotor cortices on the same dentate nucleus stimulation. In the rostral part of the premotor cortex (area 6) on the border of area 9, both types of responses were induced and admixed.The relay nucleus of the thalamus was suggested for the dentate-induced responses in the frontal association cortex.     

Electrophysiological studies of the projections from the parietal association area to the cerebellar cortex

1. Responses evoked in the cerebellar cortex by stimulation of the parietal association cortex (rostral portions of the middle suprasylvian gyrus) were recorded and analysed in cats, and were compared with those by stimulation of the motor cortex (anterior sigmoid gyrus). 2. The parietal stimulation elicited early mossy fibre and late climbing fibre responses in the cerebellar cortex. The mossy fibre responses appeared at a latency of 2.0--2.5 msec and predominantly in the lateral (hemispherical) part of the contralateral cerebellum (mainly crus I, crus II and paramedian lobules). Cutting of the inferior cerebellar peduncle produced little or no influence upon the mossy fibre responses, which suggests that the mossy fibre responses are mediated chiefly by the pontine nuclei. 3. The climbing fibre responses were recorded at a latency of 17--19 msec and markedly in the contralateral intermediate and medial parts of IV--VI lobules. The responses were easily sppressed by anaesthesia and depended on the conditions of experimental animals. The unstable appearance of the responses and their longer latencies than those of the climbing fibre responses due to stimulation of the motor cortex imply indirect pathways from the parietal association cortex to the inferior olive. 4. The predominant projection of the parietal-induced mossy fibre responses to the lateral part of the cerebellum was compared with the mossy fibre projection from the motor cortex and was discussed as an important component in the cerebrocerebellar loops.     

An autoradiographic study of cortical projections from motor thalamic nuclei in the macaque monkey.

The special areal and laminar distributions of cortical afferent connections from various thalamic nuclei in the monkey (Macaca fuscata) were studied by using the anterograde axonal transport technique of autoradiography. The following findings were obtained. The superficial thalamocortical (T-C) projections, terminating in the (superficial half of) cortical layer I, arise mainly from the nucleus ventralis anterior, pars principalis (VApc) and nucleus ventralis lateralis, pars oralis (VLo), and possibly from the nucleus ventralis lateralis, pars medialis (VLm) and nucleus ventralis anterior, pars magnocellularis (VAmc). The VApc gives rise to the superficial T-C and deep T-C projections onto the postarcuate premotor area around the arcuate genu and spur, and onto the dorsomedial part of the caudal premotor area as well as the supplementary motor area (SMA). The VApc also gives rise to only deep T-C projections onto the remaining premotor area and onto the rostral bank of the arcuate sulcus as well as the ventral bank of the cingulate sulcus at the level of the premotor area. The VLo gives rise to the superficial T-C projections onto the ventrolateral part of the motor area (mainly to the forelimb motor area) and onto the dorsomedial part to the mesial cortex at the rostral level of the motor area. The VAmc gives rise to the superficial T-C projections onto the banks of the arcuate genu and adjacent region of area 8. Area X, the nucleus ventralis posterolateralis, pars oralis (VPLo), nucleus ventralis posterolateralis, pars caudalis (VPLc), nucleus ventralis posteromedialis (VPM) and possibly the nucleus ventralis lateralis, pars caudalis (VLc) send only deep T-C projections. The dorsal and medial parts of the VLc project onto the premotor area, the rostral part of the motor area and the SMA, and also the ventral bank of the cingulate sulcus. Area X projects onto the premotor area, the SMA, and the caudal part of area 8. The thalamic relay nuclei projecting onto the frontal association cortex were found to be the VAmc, medial VLc and area X.     

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.     

An analysis of potentially converging inputs to the rostral ventral thalamic nuclei of the cat

Summary Potentially convergent inputs to cerebellar-receiving and basal ganglia-receiving areas of the thalamus were identified using horseradish peroxidase (HRP) retrograde tracing techniques. HRP was deposited iontophoretically into the ventroanterior (VA), ventromedial (VM), and ventrolateral (VL) thalamic nuclei in the cat. The relative numbers of labeled neurons in the basal ganglia and the cerebellar nuclei were used to assess the extent to which the injection was in cerebellar-receiving or basal ganglia-receiving portions of thalamus. The rostral pole of VA showed reciprocal connections with prefrontal portions of the cerebral cortex. Only the basal ganglia and the hypothalamus provided non-thalamic input to modulate these cortico-thalamo-cortical loops. In VM, there were reciprocal connections with prefrontal, premotor, and insular areas of the cerebral cortex. The basal ganglia (especially the substantia nigra), and to a lesser extent, the posterior and ventral portions of the deep cerebellar nuclei, provided input to VM and may modulate these corticothalamo-cortical loops. The premotor cortical areas connected to VM include those associated with eye movements, and afferents from the superior colliculus, a region of documented importance in oculomotor control, also were labeled by injections into VM. The dorsolateral portion of the VA-VL complex primarily showed reciprocal connections with the medial premotor (area 6) cortex. Basal ganglia and cerebellar afferents both may modulate this cortico-thalamo-cortical loop, although they do not necessarily converge on the same thalamic neurons. The cerebellar input to dorsolateral VA-VL was from posterior and ventral portions of the cerebellar nuclei, and the major potential brainstem afferents to this region of thalamus were from the pretectum. Mid- and caudo-lateral portions of VL had reciprocal connections with primary motor cortex (area 4). The dorsal and anterior portions of the cerebellar nuclei had a dominant input to this corticothalamo-cortical loop. Potentially converging brainstem afferents to this portion of VL were from the pretectum, especially pretectal areas to which somatosensory afferents project.List of Abbreviations AC central amygdaloid nucleus - AL lateral amygdaloid nucleus - AM anteromedial thalamic nucleus - AV anteroventral thalamic nucleus - BC brachium conjunctivum - BIC brachium of the inferior colliculus - Cd caudate nucleus - CL centrolateral thalamic nucleus - CM centre median nucleus - CP cerebral peduncle - CUN cuneate nucleus - DBC decussation of the brachium conjunctivum - DR dorsal raphe nuclei - EC external cuneate nucleus - ENTO entopeduncular nucleus - FN fastigial nucleus - FX fornix - GP globus pallidus - GR gracile nucleus - IC internal capsule - ICP inferior cerebellar peduncle - IP interpeduncular nucleus - IVN inferior vestibular nucleus - LD lateral dorsal thalamic nucleus - LGN lateral geniculate nucleus - LH lateral hypothalamus - LP lateral posterior thalamic complex - LRN lateral reticular nucleus - LVN lateral vestibular nucleus - MB mammillary body - MD mediodorsal thalamic nucleus - MG medial geniculate nucleus - ML medial lemniscus - MLF medial lengitudinal fasciculus - MT mammillothalamic tract - MVN medial vestibular nucleus - NDBB nucleus of the diagonal band of Broca - NIA anterior nucleus interpositus - NIP posterior nucleus interpositus - OD optic decussation - OT optic tract - PAC paracentral thalamic nucleus - PPN pedunculopontine region - PRO gyrus proreus - PRT pretectal region - PT pyramidal tract - PTA anterior pretectal region - PTM medial pretectal region - PTO olivary pretectal nucleus - PTP poterior pretectal region - Pul pulvinar nucleus - Put putamen - RF reticular formation - RN red nucleus - Rt reticular complex of the thalamus - S solitary tract - SCi superior colliculus, intermediate gray - SN substantia nigra - ST subthalamic nucleus - VA ventroanterior thalamic nucleus - VB ventrobasal complex - VL ventrolateral thalamic nucleus - VM ventromedial thalamic nucleus - III oculomotor nucleus - IIIn oculomotor nerve - 5S spinal trigeminal nucleus - 5T spinal trigeminal tract - VII facial nucleus     

Projection of precentral motor cortex upon nucleus medialis dorsalis thalami in the monkey.

The efferent connections of the lateral aspects of the precentral, premotor and granular frontal cortex were reexamined in 12 monkeys (Macaca fascicularis) by means of anterograde labelling techniques using radioactive proline and leucine. A distinct projection of the precentral gyrus upon the paralamellar portion of the nucleus medialis dorsalis (MD) was observed. The somatotopic arrangement within this projection is less well defined than within the ventrolateral thalamic complex. The facial division of area 4 has not only a marked ipsilateral but in contrast to the body representation also a distinct if much weaker contralateral projection. No label was found in MD after injections in the postcentral gyrus. Thus, MD represents a thalamic link between agranular (motor) and granular (association) cortex of the frontal lobe.     

Convergence of cerebral inputs onto dentate neurons in monkey

Summary The patterns of convergence of inputs from different areas of the cerebral cortex and the peripheral nerves onto single dentate neurons was studied in cebus monkeys. Dentate neurons receive their strongest and most numerous inputs from the premotor and supplementary motor regions of area 6. The sensorimotor and frontal cortices have weaker projections to the dentate nucleus, while peripheral nerves and many other association cortical areas were found to be ineffective in influencing cells of the lateral cerebellum. Dentate cells that respond to stimulation of hindlimb regions of the sensorimotor cortex tend to receive their principal input from the supplementary motor area and medial premotor regions, while neurons responding to forelimb sensorimotor cortex tend to receive lateral premotor inputs. In addition there is a topographical organization within the ventral pole of dentate with the hindlimb represented in the anterior regions and the forelimb in the posterior regions. These results are compared with those of similar studies of interpositus and dentate neurons in cat and monkey. The differences between the afferent inputs to dentate and interpositus are consistent with the suggestion that the lateral cerebellum is involved in programming movement parameters before movement initiation while the intermediate zone is involved in up-dating the evolving movement.     

Cerebello-cortical linkage in the monkey as revealed by transcellular labeling with the lectin wheat germ agglutinin conjugated to the marker horseradish peroxidase

Summary 1. The possibility of a cerebellar linkage, via the thalamus with medial area 6 of the cerebral cortex was further explored in the present experiments (cf. preceding companion paper). 2. It was found that HRP conjugated to the lectin wheat germ agglutinin injected into motor cortical areas was transported beyond the thalamus to the contralateral intracerebellar nuclei when the survival time was 4–7 days. 3. It is suggested that the labeling in the deep cerebellar nuclei occurred via the thalamic relay where cerebellofugal fibre terminals had taken up the marker substance released by corticothalamic fibre terminals or by the retrogradely labeled thalamic perikarya. 4. In general, transcellular labeling of perikarya was weaker than retrograde labeling in the thalamic cells. Some of the nuclear zones in the cerebellum showed relatively dense granulations of the reaction product; in other zones only cells with few granules were seen, and large parts of the nuclei were not labeled at all. 5. The topography of secondary labeling in the cerebellar nuclei depended on the cortical injection sites. In all cases, most labeling was found in the contralateral dentate nucleus. The interposed nucleus received a fair amount of heavy labeling only in the precentral arm and face cases. Very little labeling was seen in the fastigial nucleus and in the cerebellar nuclei ipsilateral to the cortical injections. A somatotopic organization of secondary labeling was noted in the precentral cases with the face being represented caudally, the hindlimb rostrally and the arm between the face and the hindlimb representation. This is in agreement with previous anatomical and electrophysiological investigations. 6. These observations thus lend support to the conclusion that the SMA receives a transthalamic input not only from the basal ganglia but also from the cerebellum, especially from its lateral, neocerebellar portion.Abbreviations AI Nucleus interpositus anterior - CM Nucleus centrum medianum - CSL Nucleus centralis lateralis superior - D Nucleus dentatus - F Nucleus fastigius - I Nucleus interpositus - MD Nucleus medialis dorsalis - NRTP Nucleus reticularis tegmenti pontis - PI Nucleus interpositus posterior - PN Griseum pontis - SMA Supplementary motor cortex - STh Nucleus subthalamicus - VLc Nucleus ventralis lateralis, pars caudalis - VLo Nucleus ventralis lateralis, pars oralis - VPLo Nucleus ventralis posterior lateralis, pars oralis - X Nucleus X     

Robust localization of the contralateral precentral gyrus in hemiparetic patients using the unimpaired ipsilateral hand: a clinical functional magnetic resonance imaging protocol

Tumor related contralateral motor deficits complicate preoperative functional magnetic resonance imaging (fMRI). In plegic patients the localization of the sensorimotor cortex is often impossible. In this context we developed a clinical fMRI protocol dedicated to patients with motor deficits using the unaffected ipsilateral hand. Based on the hypothesis that selfpaced finger movements recruit more and larger neuronal populations with rising task complexity, different motor tasks were tested regarding ipsilateral localization in ten right handed volunteers. Complex finger opposition localized the ipsilateral premotor cortex (Brodman area 6) robustly and was introduced to preoperative fMRI in hemiparetic patients as functional landmark to identify the precentral gyrus on the tumors side. Additional contralateral automated tactile stimulation localized the primary somatosensory cortex and completed the protocol.     

Stimulation of the lateral septum is a more effective conditioned stimulus than stimulation of the medial septum during classical conditioning of the eye-blink response

Eight rabbits were trained in the classically conditioned eye-blink response procedure using stimulation of the septal nuclei as the conditioned stimulus (CS). Each rabbit was trained with both medial septal stimulation and lateral septal stimulation. Stimulation of the medial septum was a far less effective CS than stimulation of the lateral septum. This effect may be due to the different roles of these two nuclei in classical conditioning. Conditioning using lateral septal stimulation as a CS is dependent on the cerebellar interpositus nucleus as is conditioning using peripheral and other brain stimulation CSs.     

The role of the cerebellum in classical conditioning of discrete behavioral responses

The cerebellum and its associated circuitry constitutes the entire essential neuronal system for classical conditioning of eye-blink and other discrete responses (e.g. limb flexion) learned with an aversive unconditioned stimulus (US) using the standard delay paradigm where the conditioned stimulus (CS) and the US coterminate. Evidence reviewed here strongly supports the following conclusions. The CS pathway involves sensory relay nuclei projections to the pontine nuclei and its mossy fiber projections to the cerebellar cortex and nuclei. The US pathway involves activation of the inferior olive (dorsal accessory olive for eye blink) and its climbing fiber projections to the cerebellar cortex and nuclei. The conditioned response (CR) pathway involves the cerebellar interpositus nucleus, the superior cerebellar peduncle pathway to the magnocellular red nucleus and rubral projections to premotor and motor nuclei generating the behavioral response. Anatomical data, neuronal unit recordings, electrical stimulation, lesions and methods of reversible inactivation all strongly support the hypothesis that the essential memory trace for the learning of these discrete conditioned responses is formed and stored in the cerebellar interpositus nucleus. Neuronal/synaptic plasticity is also established in the cerebellar cortex in this form of learning but the role of the cortex is less clear. We argue that the cortex plays a key role in normal acquisition and adaptive timing of the conditioned response, under certain circumstances, but it remains unclear exactly what features of conditioning are being encoded in the cerebellar cortex in this basic form of associative learning and memory.     

Properties of single neurons in the cat midsuprasylvian gyrus

Summary Responses of cells in the midsuprasylvian gyrus (MSSG) of cats were investigated following electrical stimulation of the central lateral nucleus (CL) of the thalamus and tooth pulp, low-threshold cutaneous or visual afferents. Electrical stimulation in CL induced excitation in many cells located in cortical areas 5 and 7. Cells in these areas also received input from somato-sensory and visual afferents. Cells in MSSG showed a wide convergence from tooth pulp, low-threshold cutaneous afferents and from the CL. The majority of wide convergent cells in area 5 were found in layers IV and V, while cells excited by CL and tooth pulp were found in layers II and III. Similarities were found between CL and tooth pulp evoked responses with regard to the excitation-inhibition pattern. The excitation evoked from CL and tooth pulp was less often followed by a hyperpolarizing potential compared to that seen after low-threshold lip, paw and visual afferent stimulation. Stimulation sites in the lateral parts of CL-evoked responses with the shortest latencies in area 5. In this part of the cortex, short latency synaptic potentials were found in cells in superficial layers. In the same area, synaptic potentials of short latency were also evoked by electrical stimulation of tooth pulp, lip and paw. Light-flash stimulation evoked responses with the shortest latencies in area 7. The results of this study demonstrate that putative nociceptive information reaches the parietal association cortex and that part of this input may be relayed via CL. We suggest that the excitatory influences of nociceptive and CL stimulation is related to behavioral arousal and attention mechanisms.Abbreviations AV anteroventral nucleus - CL central lateral nucleus - CM centre median nucleus - GL lateral geniculate nucleus - LD lateral dorsal nucleus - LP lateral posterior complex - MD mediodorsal nucleus - MSSG midsuprasylvian gyrus - OT optic tract - PAC paracentral nucleus - PF parafascicular nucleus - Po posterior thalamic nuclei - PP pes pedunculi - STT spinothalamic tract - VB ventrobasal complex - VA ventroanterior nucleus - VL ventrolateral complex - VMB basal ventromedial nucleus - VMH ventromedial hypothalamic nucleus - VPL ventroposterolateral nucleus - VPM ventroposteromedial nucleus - C.Max contralateral maxillary canine tooth - I.Max ipsilateral maxillary canine tooth - C.Mand contralateral mandibular canine tooth - I.Mand ipsilateral mandibular canine tooth - C.Lip contralateral upper lip - I.Lip ipsilateral upper lip - C.F.Paw contralateral forepaw - I.F.Paw ipsilateral forepaw - C.H.Paw contralateral hindpaw - I.H.Paw ipsilateral hindpaw - AP anteroposterior plane (in mm anterior to the interauricular plane) - ML mediolateral plane (in mm lateral to the midline)     

Integration of cerebral and peripheral inputs by interpositus neurons in monkey

Summary The patterns of convergence of cerebral and peripheral nerve inputs onto interpositus neurons were studied in cebus monkeys. The strongest inputs to interpositus neurons are from motor and somatosensory cortex, with weaker inputs from peripheral nerves and cerebral area 6. The neurons in the anterior portion of interpositus receive cerebral and peripheral inputs primarily representing the hindlimb, while inputs to neurons in the posterior division represent forelimb or mixed forelimb and hindlimb. The hindlimb neurons integrate signals principally from motor cortex, somatosensory cortex, nerves, supplementary motor and medial premotor areas, while forelimb neurons receive inputs from motor, somatosensory, lateral premotor cortical areas and nerves. The results from this study are compared with those from studies of interpositus and dentate neurons in cat and monkey in order to determine the role of n. interpositus in movement. It is suggested that the inputs integrated by interpositus neurons are consistent with a role in up-dating skilled movements.     

Input from muscle and cutaneous nerves of the hand and forearm to neurones of the precentral gyrus of baboons and monkeys

1. The precentral bank of the Rolandic fissure of the cortical arm area has been explored with extracellular micro-electrodes in primates (baboons and monkeys) under nitrous oxide and oxygen anaesthesia, supplemented by small doses of Parkesernyl(R) and chloralose. The results in baboons and monkeys were the same.2. Single units were classified as pyramidal tract neurones or non-pyramidal tract neurones according to their antidromic responsiveness to stimuli applied in the dorsolateral funiculus at C1-2.3. Responses to electrical stimulation of the deep (motor) radial nerve, the deep palmar (motor) branch of the ulnar nerve, and the superficial (cutaneous) radial nerve could be recorded in the majority of neurones of the motor cortex provided that short trains of strong stimuli were used. Minimal responses to muscle nerve stimulation were observed in a few neurones at 1.4 x group I threshold, but most units reacted only with higher stimulus intensities (2-3 x group I threshold).4. The latencies to peripheral nerve stimulation were measured from the first peak of the incoming volley recorded at the root entry zone. The mean response latencies of pyramidal tract cells were between 20 and 25 msec; non-pyramidal tract cells were activated at slightly shorter mean latencies, the difference being significant for superficial radial nerve stimulation only (4 msec). These latencies are more than twice as long as those recorded in the postcentral gyrus, and the probability of discharge is lower than for postcentral neurones.5. A further difference between neurones of the postcentral and precentral gyrus is the pronounced convergence from different nerves and also from different modalities (cutaneous and muscle afferents) in units of the precentral cortex in contrast to units of the postcentral cortex.6. The high thresholds, necessary to activate precentral neurones by muscle nerve stimulation, make it unlikely that group I muscle afferents are involved. This is, furthermore, indicated by the lack of responsiveness to intravenous injection of succinylcholine which was, however, effective for driving neurones of the specific projection area for group I afferents, area 3a. The present experiments are consistent with the view that sensitivity of precentral neurones to muscle stretch (described in previous studies) is due to activation of secondary muscle spindle endings and their ascending pathways.7. The original hypothesis of a load compensating ;pyramidal reflex' with an oligosynaptic afferent contribution from the spindle primaries can be discarded. The present findings indicate that there is a feed-back from secondary muscle spindle afferents which, by way of a more complex pathway, can modulate the firing frequency of neurones in the motor cortex.     

Learning- and cerebellum-dependent neuronal activity in the lateral pontine nucleus

The effects of inactivation of cerebellar deep nuclei and the lateral pontine nucleus on classical eyeblink conditioning with tone or lateral reticular nucleus (LRN) stimulation as conditioned stimuli (CSs) were examined. Inactivation of cerebellar deep nuclei abolished eyeblink conditioned responses (CRs) when the CS was either a tone or LRN stimulation. Inactivation of the lateral pontine nucleus prevented only the acquisition and retention of tone-evoked eyeblink CRs. Multiple-unit recording demonstrated that when LRN stimulation was used as the CS, inactivation of the interpositus nucleus abolished learning-related neuronal activity in the lateral pontine nucleus, whereas inactivation of pontine nucleus had little effect on similar activity in the interpositus nucleus. Thus, the learning-induced neuronal activity in the lateral pontine nucleus was most likely driven by the cerebellar interpositus nucleus.     

Dopaminergic and non-dopaminergic neurons in the ventral tegmental area of the rat project, respectively, to the cerebellar cortex and deep cerebellar nuclei.

It has been suggested recently that dopamine in the cerebellum not only acts as a precursor for noradrenaline in afferent fibers supplied by locus coeruleus neurons, but also subserves an independent transmitter role in a separate neural system. The present study was initiated to investigate the possible sources for dopaminergic innervation of the cerebellum. Employing anterograde and retrograde axonal tracing with cholera toxin and a combination of fluorescent retrograde axonal tracing with Fluoro-Gold and tyrosine hydroxylase immunofluorescence histochemistry, we found in the rat that the ventral tegmental area, containing the A10 dopaminergic cell group, sends projection fibers to the cerebellum bilaterally with a slight contralateral predominance. The projections from the ventral tegmental area to the cerebellum were segregated into the dopaminergic one to the cerebellar cortex and the non-dopaminergic one to the deep cerebellar nuclei. Dopaminergic fibers projecting from the ventral tegmental area to the cerebellar cortex terminated mainly in the granular layer, additionally in the Purkinje cell layer, but not at all in the molecular layer. They were distributed predominantly in the crus I ansiform lobule and paraflocculus, and to a lesser extent in the crus II ansiform lobule. On the other hand, non-dopaminergic fibers projecting from the ventral tegmental area to the deep cerebellar nuclei were seen to terminate mainly in the lateral nucleus, to a lesser extent in the interpositus nucleus, but not at all in the medial nucleus. The ventral tegmental area was also observed to receive projection fibers from the lateral and interpositus cerebellar nuclei bilaterally with a contralateral predominance. The projections from the ventral tegmental area to the cerebellum revealed in the present study might exert limbic influences upon the cerebro-cerebellar loops subserving the execution and co-ordination of voluntary movements.     

Differential projection from the motor and limbic cortical regions to the mediodorsal thalamic nucleus in the dog

The cortical afferents to the mediodorsal thalamic nucleus in the dog were studied by using horseradish peroxidase. Small injections allowed to establish two specific projection zones connected separately with the lateral and medial segments of the nucleus. The lateral segment received the major projection from the dorsal half of the hemisphere. It included premotor and part of the motor cortices in the anterior sigmoid gyrus and precruciate areas as well as the presylvian cortex. The medial segment of the nucleus was innervated by the limbic areas of the ventral half of the hemisphere. These areas included the medioventrally located genual, subcallosal and piriform cortices, as well as the cortex of the ventral bank of the anterior rhinal sulcus and the caudal part of the orbital gyrus. The cortical fields situated between these two main cortical zones, both on the lateral and medial surfaces (rhinal and sylvian sulci and anterior cingular gyrus, respectively) sent projections to both medial and lateral segments of the nucleus. These results indicate that in the mediodorsal thalamic nucleus may take place the integration of information from two functionally defined systems, the motor and limbic ones.