Parallel fibre receptive fields of Purkinje cells and interneurons are climbing fibre-specific.

In cats decerebrated at the intercollicular level, the cutaneous parallel fibre receptive fields of Purkinje cells, molecular layer interneurons and Golgi cells in the cerebellar C3 zone were delineated by natural stimulation of the skin during extracellular unitary recordings. The locations of these receptive fields were compared with the climbing fibre receptive field of the local Purkinje cell and with the receptive fields of other neurons located along a beam of parallel fibres. The parallel fibre receptive fields of these neurons were highly specific to the local climbing fibre receptive field. In Purkinje cells, the parallel fibre receptive fields were located outside the climbing fibre receptive field of the same cell. In contrast, the parallel fibre receptive fields of interneurons were similar to the receptive field of the locally terminating climbing fibres. In both types of neurons, the parallel fibre receptive fields were small and had distinct borders. The location on the skin of the parallel fibre receptive fields differed conspicuously between neighbouring Purkinje cells and between neighbouring interneurons along a beam as well as between Purkinje cells and interneurons in the same electrode tracks. The remarkable specificity between the parallel fibre receptive fields in Purkinje cells and interneurons and the receptive field of the local climbing fibre is most easily explained by different forms of parallel fibre synaptic plasticity.

Topographical organization of projections to cat motor cortex from nucleus interpositus anterior and forelimb skin.

1. The activation of the motor cortex from focal electrical stimulation of sites in the forelimb area of cerebellar nucleus interpositus anterior (NIA) was investigated in barbiturate-anaesthetized cats. Using a microelectrode, nuclear sites were identified by the cutaneous climbing fibre receptive fields of their afferent Purkinje cells. These cutaneous receptive fields can be identified by positive field potentials reflecting inhibition from Purkinje cells activated on natural stimulation of the skin. Thereafter, the sites were microstimulated and the evoked responses were systematically recorded over the cortical surface with a ball-tipped electrode. The topographical organization in the motor cortex of responses evoked by electrical stimulation of the forelimb skin was also analysed. 2. Generally, sites in the forelimb area of NIA projected to the lateral part of the anterior sigmoid gyrus (ASG). Sites in the hindlimb area of NIA also projected to lateral ASG and in addition to a more medial region. Sites in the face area of NIA, however, projected mainly to the middle part of the posterior sigmoid gyrus (PSG). 3. For sites in the forelimb area of NIA, the topographical organization and strength of the projections varied specifically with the cutaneous climbing fibre receptive field of the site. The largest cortical responses were evoked from sites with receptive fields on the distal or ventral skin of the forelimb. 4. Microelectrode recordings in the depth of the motor cortex revealed that responses evoked by cerebellar nuclear stimulation were due to an excitatory process in layer III. 5. Short latency surface responses evoked from the forelimb skin were found in the caudolateral part of the motor cortex. At gradually longer latencies, responses appeared in sequentially more rostromedial parts of the motor cortex. Since the responses displayed several temporal peaks that appeared in specific cortical regions for different areas of the forelimb skin, several somatotopic maps were seen. 6. The cerebellar and cutaneous projections activated mainly different cortical regions and had topographical organizations that apparently were constant between animals. Their patterns of activation may constitute a frame of reference for investigations of the functional organization of the motor cortex.

Cutaneous receptive fields and topography of mossy fibres and climbing fibres projecting to cat cerebellar C3 zone.

1. The topographical organization of mossy fibre input to the forelimb area of the paravermal C3 zone in cerebellar lobules IV and V was investigated in barbiturate-anaesthetized cats and compared with the previously described microzonal organization of climbing fibre input to the same part of the cortex. Recordings were made in the Purkinje cell and granule cell layers from single climbing fibre and mossy fibre units, respectively, and the organization of cutaneous receptive fields was assessed for both types of afferents. 2. Based on spatial characteristics, receptive fields of single mossy fibres could be systematized into ten classes and a total of thirty-two subclasses, mainly in accordance with a scheme previously used for classification of climbing fibres. Different mossy fibres displayed a substantial range of sensitivity to natural peripheral stimulation, responded preferentially to phasic or tonic stimuli and were activated by brushing of hairs or light tapping of the skin. 3. Overall, mossy fibres to any given microzone had receptive fields resembling the climbing fibre receptive field defining that microzone. However, compared with the climbing fibre input, the mossy fibre input had a more intricate topographical organization. Mossy fibres with very similar receptive fields projected to circumscribed cortical regions, with a specific termination not only in the mediolateral, but also in some cases in the rostrocaudal and dorsoventral, dimensions of the zone. On the other hand, mossy fibre units with non-identical, albeit usually similar, receptive fields were frequently found in the same microelectrode track.

The control of forelimb movements by intermediate cerebellum.

In a series of studies, the functional organization of cerebellar regions contributing to the control of forelimb movements via the rubro- and corticospinal tracts has been characterized in the cat. The system consists of the cerebellar cortical C1, C3 and Y zones and their efferent intracerebellar nucleus, the interpositus anterior. Based on analyses of cutaneous and muscle afferent climbing fibre input, of corticonuclear connections and of limb movements controlled, a modular organization of this cerebellar control system is proposed. Each module consists of a number of cortical microzones, defined by their homogeneous climbing fibre input, and a group of neurones in nucleus interpositus anterior on which these microzones converge. The input to climbing fibres is multi-modal and originates from cutaneous A beta (tactile), A delta and C (nociceptive) fibres and from muscle afferents. The cutaneous receptive fields have spatial characteristics suggestive of a relation to elemental movements. For most climbing fibres, the spatial relationship between cutaneous and muscle afferent input is such that the muscle afferent input originates from muscles that, if activated, would tend to move the cutaneous receptive field of the climbing fibre towards a stimulus applied to the skin. By contrast, the limb movement controlled by the module often has the opposite direction, and would thus tend to move the cutaneous receptive field away from a stimulus applied to the skin. Functional implications of this organization for the involvement of these regions in acute and adaptive motor control of limb movements are discussed.

Relation between cutaneous receptive fields and muscle afferent input to climbing fibres projecting to the cerebellar C3 zone in the cat.

Inferior olivary cells projecting as climbing fibres to the forelimb area of the cerebellar C3 zone were investigated with respect to their cutaneous and muscle afferent input in barbiturate-anaesthetized cats. Climbing fibre responses were recorded from single cerebellar cortical Purkinje cells on natural stimulation of the skin and on electrical stimulation of nerves to m. biceps brachii, m. triceps brachii and to nine muscles acting as dorsal or palmar flexors of the paw (and, in some cases, the digits). The analysis was focused on the functional organization of convergence between cutaneous and muscle afferents onto single olivary neurons. Cutaneous receptive fields on the dorsal side of the paw and on the digits were generally associated with moderate to strong input from dorsal flexors, but little or no input from palmar flexors or proximal muscles. Receptive fields on the ventral side of the paw and forearm were associated with relatively strong input from biceps and palmar flexors. Climbing fibres with cutaneous receptive fields extending on the ulnar side of the paw and forearm usually received strong input from the triceps and moderate to strong input from dorsal flexors, whereas input from the palmar flexors was weak or lacking. In conclusion, the results indicate that the cutaneous receptive fields in many cases are associated with input from muscles the action of which would tend to move the receptive field towards a stimulus applied to the skin.

Functional relation between corticonuclear input and movements evoked on microstimulation in cerebellar nucleus interpositus anterior in the cat.

The functional relation between receptive fields of climbing fibres projecting to the C1, C3 and Y zones and forelimb movements controlled by nucleus interpositus anterior via the rubrospinal tract were studied in cats decerebrated at the pre-collicular level. Microelectrode tracks were made through the caudal half of nucleus interpositus anterior. This part of the nucleus receives its cerebellar cortical projection from the forelimb areas of these three sagittal zones. The C3 zone has been demonstrated to consist of smaller functional units called microzones. Natural stimulation of the forelimb skin evoked positive field potentials in the nucleus. These potentials have previously been shown to be generated by climbing fibre-activated Purkinje cells and were mapped at each nuclear site, to establish the climbing fibre receptive fields of the afferent microzones. The forelimb movement evoked by microstimulation at the same site was then studied. The movement usually involved more than one limb segment. Shoulder retraction and elbow flexion were frequently evoked, whereas elbow extension was rare and shoulder protraction never observed. In total, movements at the shoulder and/or elbow occurred for 96% of the interpositus sites. At the wrist, flexion and extension movements caused by muscles with radial, central or ulnar insertions on the paw were all relatively common. Pure supination and pronation movements were also observed. Movements of the digits consisted mainly of dorsal flexion of central or ulnar digits. A comparison of climbing fibre receptive fields and associated movements for a total of 110 nuclear sites indicated a general specificity of the input-output relationship of this cerebellar control system. Several findings suggested that the movement evoked from a particular site would act to withdraw the area of the skin corresponding to the climbing fibre receptive field of the afferent microzones. For example, sites with receptive fields on the dorsum of the paw were frequently associated with palmar flexion at the wrist, whereas sites with receptive fields on the ventral side of the paw and forearm were associated with dorsiflexion at the wrist. Correspondingly, receptive fields on the lateral side of the forearm and paw were often associated with flexion at the elbow, whereas sites with receptive fields on the radial side of the forearm were associated with elbow extension. The proximal movements that were frequently observed also for distal receptive fields may serve to produce a general shortening of the limb to enhance efficiency of the withdrawal. It has previously been suggested that the cerebellar control of forelimb movements via the rubrospinal tract has a modular organisation. Each module would consist of a cell group in the nucleus interpositus anterior and its afferent microzones in the C1, C3 and Y zones, characterised by a homogenous set of climbing fibre receptive fields. The results of the present study support this organisational principle, and suggest that the efferent action of a module is to withdraw the receptive field from an external stimulus. Possible functional interpretations of the action of this system during explorative and reaching movements are discussed.

Topographical organization of the cerebellar cortical projection to nucleus interpositus anterior in the cat.

1. A new methodological approach for detailed study of the organization of the cerebellar corticonuclear projection was evaluated in barbiturate-anaesthetized cats. Extracellular field potentials were simultaneously recorded in nucleus interpositus anterior and in the forelimb area of the C3 zone, at the cerebellar surface. On electrical and natural stimulation of the forelimb skin, the evoked positive field potentials in the nucleus and the climbing fibre field potentials in the cerebellar cortex had similar characteristics, indicating that the nuclear potentials were related to climbing fibre activity. 2. Application of a local anaesthetic to the cerebellar surface reversibly diminished the positive field potentials in the nucleus, demonstrating that the potentials were dependent on cerebellar cortical activity. It was thus concluded that the positive field potentials were mainly generated by climbing fibre-activated Purkinje cells and reflected synaptic inhibitory potentials in nuclear neurones. Accordingly, the positive field potentials in the nucleus could be used to reveal the termination area of Purkinje cells activated by a specific climbing fibre input evoked on peripheral stimulation. 3. The topographical organization of the cerebellar cortical projection to the forelimb part of nucleus interpositus anterior was then investigated by systematically mapping the cutaneous tactile and nociceptive 'receptive fields' of the positive field potentials at different sites in the nucleus. Five groups of receptive fields were distinguished and tentatively divided into a total of nineteen subgroups. 4. Each group of receptive fields corresponded to one or two of the previously described receptive field classes of climbing fibres to the C1, C3 and Y zones and was represented in a single area of the nucleus. Within each area there was an orderly representation of different receptive fields. The results suggest that microzones in the C1, C3 and Y zones with similar climbing fibre input project to a common set of neurones in nucleus interpositus anterior. 5. We propose a modular organization for the cerebellar control of forelimb movements through the rubrospinal tract. Each module would consist of a set of neurones in nucleus interpositus anterior and their afferent microzones in the C1, C3 and Y zones. A module would control a specific group of muscles and receive a homogeneous climbing fibre input related to the movement controlled.

Distribution of Cutaneous Nociceptive and Tactile Climbing Fibre Input to Sagittal Zones in Cat Cerebellar Anterior Lobe.

Climbing fibres projecting to the cerebellar C3 zone (and the related C1 and Y zones) receive spatially well organized tactile and nociceptive inputs from the skin. In the present study, cutaneous tactile and nociceptive input to climbing fibres projecting to the X, B, C2 and D1 zones in lobule V were investigated in pentobarbitone-anaesthetized cats. From the present results and previous studies, it is concluded that the X, C1, CX, C3 and Y zones receive cutaneous nociceptive climbing fibre input. By contrast, climbing fibres to the B, C2 and D1 zones lack cutaneous nociceptive input. Tactile input was found in all zones. The spatial organization of receptive fields of climbing fibres projecting to the X and D1 zones was similar to that in the C3 zone. They were located on the ipsilateral forelimb, mainly its lateral and distal parts, and their proximal borders were located close to joints. In the B zone, more than half of the receptive fields of climbing fibres were confined to the ipsilateral hind- or forelimb. However, frequently more than one limb and parts of the trunk were included. In the C2 zone, the majority of climbing fibres had distal ipsi- or bilateral receptive fields on the forelimbs, often also including the head/face. Some of the bilateral forelimb receptive fields additionally included the hindlimbs ipsi- or bilaterally. The results indicate that each zone has a characteristic set of climbing fibre receptive fields, which is probably related to its efferent control functions.

Topography and nociceptive receptive fields of climbing fibres projecting to the cerebellar anterior lobe in the cat.

1. The cutaneous receptive fields of 225 climbing fibres projecting to the forelimb area of the C3 zone in the cerebellar anterior lobe were mapped in the pentobarbitone-anaesthetized cat. Responses in climbing fibres were recorded as complex spikes in Purkinje cells. 2. A detailed topographical organization of the nociceptive climbing fibre input to the C3 zone was found. In the medial C3 zone climbing fibres with receptive fields covering proximal and/or lateral parts of the forelimb projected most medially. Climbing fibres with receptive fields located more medially on the forelimb projected successively more laterally. The sequence of receptive fields found in the lateral C3 zone was roughly the reverse of that in the medial C3 zone. Climbing fibres with receptive fields restricted to the digits projected preferentially to the caudal part of the forelimb area, whereas those with receptive fields covering both proximal and ventral areas of the forearm projected to more rostral parts. 3. The representation of the forelimb was uneven. Receptive fields with a focus on the digits or along the lateral side of the forearm dominated. 4. The proximal borders of the receptive fields were located close to joints. The area from which maximal responses were evoked was usually located eccentrically within the receptive field. Based on spatial characteristics the receptive fields could be divided into eight classes, which in turn were tentatively divided into subclasses. Similar subclasses of receptive fields were found in different cats. This classification was further supported by the results of a quantitative analysis of eighty-nine climbing fibres. The receptive fields of these climbing fibres were mapped with standardized noxious stimulation. 5. Climbing fibres terminating within sagittal strips (width, 100-300 microns; length, greater than 1 mm) had receptive fields which belonged to the same subclass. There were commonly abrupt changes in receptive fields between such microzones. Most classes of receptive fields were found in both the medial and the lateral parts of the C3 zone. However, receptive fields with a focus on the ventral side of either the metacarpals, the wrist or the forearm were found only in the medial part of the C3 zone. Furthermore, the class of receptive fields restricted to the lateral side of the upper arm and shoulder was only found in the lateral part of the C3 zone. 6. In the discussion, it is proposed that climbing fibres projecting to each microzone carry information from spinal multireceptive reflex arcs acting on a single muscle or a group of synergistic muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

The postsynaptic dorsal column pathway mediates cutaneous nociceptive information to cerebellar climbing fibres in the cat.

1. The location in the spinal cord of the pathway mediating cutaneous nociceptive C fibre input to climbing fibres projecting to the forelimb area of the C3 zone in the cerebellar anterior lobe was investigated in pentobarbitone-anaesthetized cats. Lesions of the spinal cord at the segmental level of C3 sparing the dorsal funiculi (DF preparation) or lesions of the ipsilateral and part of the contralateral dorsal funiculi were made. 2. In the DF preparation, the cutaneous input to climbing fibres projecting to the C3 zone was the same as in cats with an intact spinal cord. Also, the topography of tactile and nociceptive receptive fields and the distribution of A- and C fibre-evoked climbing fibre field potentials was similar to that in cats with an intact spinal cord. 3. In cats with an initially intact spinal cord the cutaneous nociceptive C fibre input and the topographically well organized tactile input to the C3 climbing fibres disappeared following a lesion of the ipsilateral and part of the contralateral dorsal funiculi. Following this lesion the receptive fields of the climbing fibres became indistinct and only irregular responses were evoked on skin stimulation. 4. It is concluded that the cutaneous nociceptive C fibre input from the forelimb to climbing fibres projecting to the C3 zone is mediated by the ipsilateral dorsal funiculus. Since cutaneous C fibres terminate exclusively in the spinal cord close to their entrance zone the postsynaptic dorsal column pathway must be part of this spino-olivocerebellar pathway.

The lateral reticular nucleus in the cat. VI. Excitatory and inhibitory afferent paths.

The afferent paths from the spinal cord and from trigeminal afferents to the lateral reticular nucleus (LRN) were investigated by intracellular recording from 204 LRN neurones in preparations with a spinal cord lesion at C3 that spared only the ipsilateral ventral quadrant. Stimulation of nerves in the limbs evoked EPSPs and JPSPs in 201 of 204 tested LRN neurones. The strongest input was from the ipsilateral forelimb (iF) which evoked EPSPs in 49% and IPSPs in 73% of the LRN neurones. Each of the other limbs evoked EPSPs in approximately 20% and IPSPs in approximately 25% of the neurones. Stimulation of the ipsilateral trigeminal nerve (iTrig) evoked EPSPs in 32% and IPSPs in 46% of the neurones. The shortest latencies of the EPSPs and IPSPs indicated a disynaptic connection between primary afferents in the iF and iTrig and the LRN. The most direct pathways for excitatory and inhibitory responses from the other limbs were trisynaptic. Stimulation of the ventral part of the ipsilateral funiculus (iVLF) at C3 (C3iVLF) evoked monosynaptic responses in 189 of 201 tested LRN neurones. Monosynaptic EPSPs were recorded in 104 neurones and monosynaptic IPSPs in 126 neurones. Monosynaptic EPSPs and IPSPs were encountered in all parts of the LRN. Stimulation of the iVLF at L1 (L1iVLF) evoked monosynaptic EPSPs and IPSPs in the ventrolateral part of the LRN. The termination areas of excitatory and inhibitory fibres appeared to be the same. LRN neurones without monosynaptic EPSPs or IPSPs from the L1iVLF were located mainly in the dorsal part of the magnocellular division. Stimulation of the dorsal funiculi (DF) at C2 and the ipsilateral trigeminal nerve (iTrig) evoked excitatory and inhibitory responses in the LRN. The shortest latencies of EPSPs and IPSPs indicated disynaptic connections.

The lateral reticular nucleus in the cat. VII. Excitatory and inhibitory projection from the ipsilateral forelimb tract (iF tract).

Intracellular recording from neurones in the lateral reticular nucleus (LRN) demonstrated that, in addition to the previously identified excitatory ipsilateral forelimb tract (iF tract) (Clendenin et al. 1974c) there is an inhibitory tract mediating information from the ipsilateral forelimb to the LRN. The excitatory and inhibitory tracts were similarly organized. The tract neurones were monosynaptically activated by afferents in the ipsilateral forelimb and projected to the same area of the LRN. They will be considered as excitatory and inhibitory components of the iF tract and denoted the excitatory and inhibitory iF tract (EiF and IiF tracts). Stimulation of the descending ipsilateral dorsolateral funiculus (iDLF) in the C3 segment evoked disynaptic EPSPs and IPSPs in LRN neurones contacted by the EiF and IiF tracts. The responses in individual LRN neurones evoked from the iDLF were similar to the responses evoked from the forelimb nerves suggesting that the EiF and IiF tracts are monosynaptically activated by fibres in the iDLF. The dorsal portion of the magnocellular part of the LRN constituted the main termination area of both the EiF and IiF tracts. Neurones in this area have previously been shown to project ipsilaterally to lobule V in the pars intermedia of the cerebellar anterior lobe and to the paramedian lobule (Clendenin et al. 1974a). IPSPs evoked from the IiF tract in LRN neurones outside the main termination area had smaller amplitudes and longer latencies. This finding suggests that these responses were generated by thin axon collaterals given off from dorsally located stem axons.

The lateral reticular nucleus in the cat. VIII. Excitatory and inhibitory projection from the bilateral ventral flexor reflex tract (bVFRT).

Intracellular recordings were obtained from 204 neurones in the lateral reticular nucleus (LRN). LRN neurones contacted by the bVFRT were identified by the responses evoked on stimulation of descending fibres in the contralateral ventral quadrant of the spinal cord (cVQ) at cervical (C5cVQ) and lumbar (L2cVQ) levels. Stimulation of the cVQ evoked excitatory or inhibitory responses in 124 of the 204 LRN neurones. EPSPs were evoked in 45, IPSPs in 52 and both EPSPs and IPSPs in 27 LRN neurones. The shortest latencies of the responses evoked from the cVQ indicated that both EPSPs and IPSPs were disynaptic. This finding was confirmed by direct stimulation of the ascending fibres in the ipsilateral ventrolateral funiculus at C3 (C3iVLF) or L1 (L1iVLF). In most LRN neurones activated or inhibited from the cVQ, stimulation of the iVLF evoked similar responses at a monosynaptic latency. These results indicate that the bVFRT consists of roughly equally large groups of excitatory and inhibitory neurones monosynaptically connected with the LRN. Excitatory and inhibitory bVFRT neurones had similar peripheral receptive fields and termination areas in the LRN. LRN neurones were divided into those contacted by cervical bVFRT neurones and lumbar bVFRT neurones. The former group consisted of LRN neurones responding to C5cVQ stimulation at latencies below 5 ms, whereas the latter group contained LRN neurones responding to stimulation of the L2cVQ. Cervical bVFRT neurones projected to most parts of the LRN whereas the projection of lumbar bVFRT neurones were confined to the ventrolateral part of the nucleus. Excitatory and inhibitory vVFRT neurones of each group had similar termination areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation parameters influencing climbing fibre induced long-term depression of parallel fibre synapses.

It has been demonstrated that conjunctive stimulation of cerebellar climbing fibres and parallel fibres induces a long-term depression (LTD) of the transmission from the activated parallel fibres to Purkinje cells. The aim of the present investigation with extracellular recordings from single Purkinje cells was to study factors influencing the induction of LTD. Climbing fibres and parallel fibres were conjunctively stimulated with a constant time interval between the climbing fibre and parallel fibre stimuli. It was demonstrated that the maximal effective time interval between climbing fibre and parallel fibre activation for induction of LTD was between 125 and 250 ms. It was also demonstrated that the amplitude of the LTD depended on the stimulation frequency. The LTD induced by conjunctive stimulation at 1 and 2 Hz had a similar size whereas the LTD induced by 4 Hz was stronger.

Climbing fibres projecting to cat cerebellar anterior lobe activated by cutaneous A and C fibres.

1. Climbing fibre responses evoked on stimulation of the ipsilateral superficial radial nerve were examined in the forelimb area of the C3 zone in the barbiturate-anaesthetized cat. Climbing fibre responses were recorded in sixty-five Purkinje cells and as field potentials from the surface of the cerebellum. 2. In addition to the previously described A beta-fibre-evoked climbing fibre response, late climbing fibre responses were consistently evoked in all Purkinje cells studied when C fibres were stimulated. The latencies of the A beta- and C-fibre-evoked climbing fibre responses were 11-20 ms and 110-220 ms, respectively. In most experiments climbing fibre responses with an intermediate latency (20-30 ms) were evoked. It was demonstrated that this response depended on A delta fibres. 3. The long-latency climbing fibre response generated by electrical stimulation at C-fibre strength was evoked also during selective anodal block of conduction in A fibres (Brown & Hamman, 1972). Hence, impulses in C fibres were sufficient for generation of climbing fibre responses. 4. The distribution within the forelimb area of the C3 zone of the A beta- and C-fibre-evoked climbing fibre field potential was similar. No climbing fibre response was evoked in this area of the C3 zone by stimulation of A and C fibres in the contralateral superficial radial nerve or in the plantar nerves of the hind limbs. 5. It can be concluded that climbing fibres projecting to the forelimb area of the C3 zone in the cerebellum receive a somatotopically organized input from both A beta and C fibres.

Stimulation of cat cutaneous nociceptive C fibres causing tonic and synchronous activity in climbing fibres.

1. The input from cutaneous nociceptors to climbing fibres projecting to the forelimb area of the C3 zone in the cerebellar anterior lobe was examined in barbiturate-anaesthetized cats. Climbing fibre responses were simultaneously recorded in single Purkinje cells and as field potentials from the cerebellar surface close to these cells. 2. The cutaneous receptive field of the climbing fibres studied were located on the ipsilateral forelimb. All climbing fibres were activated by both non-noxious tactile stimulation and noxious pinch of the skin. The location of the receptive field and the distribution of sensitivity in the receptive field appeared to be identical for noxious and tactile stimuli. 3. A phasic response in the climbing fibres was evoked by either short- or long-lasting non-noxious pressure applied to their cutaneous receptive field. By contrast, all climbing fibres studied were strongly and tonically activated (up to 4-11 Hz for the duration of the stimulation) by sustained noxious pinch in the most sensitive area of their receptive fields. 4. Experiments with anodal block of impulse conduction in myelinated fibres indicated that a major input to climbing fibres during sustained noxious pinch originates from nociceptive C fibres. 5. Sustained noxious pinch of the skin evoked large field potentials on the cerebellar surface. These field potentials were evoked simultaneously with climbing fibre responses in single Purkinje cells and were due to synchronous activation of many climbing fibres. These field potentials and discharges in single climbing fibres were elicited from the same area of the skin suggesting that many of the synchronously discharging climbing fibres have the same receptive field on the skin.

Long-term depression of parallel fibre synapses following stimulation of climbing fibres.

The results from several investigations suggest that climbing fibres heterosynaptically depress parallel fibre responses in Purkinje cells. In the present investigation the mechanism behind the depression has been studied by extracellular recording of responses in single Purkinje cells, evoked by electrical stimulation of parallel fibres and climbing fibres. The results show that a short time of conjunctive stimulation of climbing fibres and parallel fibres results in a long-lasting depression of the parallel fibre responses and that this depression can be prevented if the Purkinje cells are inhibited during the conjunctive stimulation. Since inhibition has been shown to shorten or abolish the long-lasting plateau potentials which are evoked by climbing fibre impulses this finding supports the assumption that the climbing fibre evoked plateau potentials mediate the heterosynaptic depression of parallel fibre responses.

Interaction between responses in Purkinje cells evoked by climbing fibre impulses and parallel fibre volleys in the cat.

The plateau-like depolarizing potentials evoked in Purkinje cell dendrites by impulses in climbing fibres (Ekerot & Oscarsson, 1981) were conditioned by single parallel fibre volleys and investigated by intra- and extracellular recording from cat cerebellar cortex. The conditioning parallel fibre volleys evoked predominantly inhibitory potentials of long duration in the Purkinje cell dendrites. Massive parallel fibre volleys, which may evoke plateau-like depolarizing potentials (Campbell, Ekerot, Hesslow & Oscarsson, 1983) were avoided. In proximal dendrites parallel fibre volleys preceding climbing fibre responses reduced or abolished the plateau potential, whereas the initial spike-like component of the climbing fibre responses was largely unaffected. Parallel fibre stimulation during already established plateau potentials immediately terminated the plateaus. In distal dendrites parallel fibre stimulation preceding climbing fibre responses reduced or abolished both the plateau potential and the initial component of the climbing fibre responses. Parallel fibre stimulation during established plateau potentials did not immediately terminate the plateau potentials but reduced their duration. The results of the present investigation suggest that single dendritic branches of Purkinje cells serve as independent integrators of mossy fibre and climbing fibre inputs.

Dendritic plateau potentials evoked in Purkinje cells by parallel fibre volleys in the cat.

Responses evoked in Purkinje cell dendrites by parallel fibre volleys and climbing fibre impulses were investigated by intra- and extracellular recording from cat cerebellar cortex. The depth distribution of recording sites suggested that the intracellular recordings were predominantly from proximal dendrites whereas the extracellular recordings were predominantly from distal dendrites. Parallel fibre stimulation evoked monosynaptic excitation and disynaptic inhibition in the dendrites and, at higher strength, prolonged plateau-like responses in distal dendrites but only rarely in proximal dendrites. However, when the inhibitory synapses were blocked with topically applied picrotoxin, parallel fibre volleys evoked plateau potentials also in proximal dendrites. The duration of the parallel-fibre-evoked plateau potentials in distal dendrites was prolonged by increasing the intensity of the eliciting stimulus or by increasing the number of stimuli. A similar prolongation in the duration of climbing-fibre-evoked plateau potentials was observed when brief repetitive stimulation was applied to the inferior olive. The investigation provided evidence that under physiological conditions plateau potentials in Purkinje cell dendrites are exclusively evoked by climbing fibre impulses.