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This paper gives an account of single Purkyně cell responses when three types of mechanical stimulation, as in the previous paper, are applied to the forefoot and hindfoot of the decerebrate unanesthetized cat. Attention was concentrated on the effects of brief mechanical pulses to the footpad. Recording was extracellular by glass microelectrodes and special precautions were taken in identifying the spike responses as being due to a single Purkyně cell and in securing its effective isolation for our computer averaging techniques, as described in the previous papers. All Purkyně cells were in the ipsilateral anterior lobe in the lateral vermis or pars intermedia of lobules III, IV, V, except for a few recordings in the extreme rostral zone of lobule VI. Mechanical pulses or taps evoked responses from many Purkyně cells which were pure excitatory, pure inhibitory or admixtures thereof. The latencies of onset were usually in the range of 12-20 msec from the onset of the tap, which tends to be a little longer than the observed latencies for mossy fiber responses described in the preceding paper. There was often a considerable difference in the sizes of the responses evoked from different pads of the same foot, and the usual threshold for response was below 0.2 mm amplitude. Durations of responses were usually 10-20 msec for excitation and 50-100 msec for inhibition. Pressure pulses to the central foot pads of 2 sec duration evoked a wide variety of responses: brief phasic at 'on' and 'off' that could be admixtures of excitation and inhibition; almost pure tonic excitations or inhibitions that were well maintained during the 2 sec; phasic-tonic responses in various relative degrees. Usually 500 g was maximally effective and the threshold was below 100 g. Hair receptors were stimulated preferentially by brief air jets, there being brief excitatory or inhibitory responses much as with taps, but with rather longer latency. The effective area was usually fairly extensive over the hairy skin of the foot. In general the effects on Purkyně cells by cutaneous mechanoreceptors acting via mossy fibers were in accord with the mossy fiber responses reported in the preceding paper and with the well-known excitatory and inhibitory effects that are exerted by mossy fiber inputs on Purkyně cells. [ABSTRACT FROM AUTHOR]

The 275 Purkyně cells identified by the criteria of the previous paper have been investigated with respect to their role as units integrating the input to the anterior lobe from various limb nerves. The discharges from single Purkyně cells have been studied in lightly anesthetized (pentothal) or in decerebrate unanesthetized cats, there being averaging usually of 128 responses in the form of post-stimulus time histograms and cumulative frequency distributions. Single Purkyně cells exhibited a wide variation in their responses to the diverse inputs from the various afferent nerves. Attention was focussed on excitatory and inhibitory responses evoked by mossy fibers with a short latency, usually 10-15 msec for hindlimb afferents. With most Purkyně cells these responses were predominantly evoked from cutaneous nerves, low threshold fibers being particularly effective. A few Purkyně cells were preponderantly excited by afferent volleys from muscle nerves, but there was a large group with a mixed input from cutaneous and muscle nerves. Graded strengths of stimulation of muscle nerves showed that sometimes group I volleys were prepotent, but other Purkyně cells were selectively excited by group II volleys. Though sometimes the afferent volleys from antagonistic muscles had a reciprocal action on a Purkyně cell, as on a motoneurone, it was more common to find similar actions. Also convergence of inputs from forelimb and hindlirnb nerves, both cutaneous and muscular, was not uncommon, particularly in marginal areas between hindlimb and forelimb zones. A special design feature is the convergence onto a Purkyně cell of mossy fiber and climbing fiber inputs evoked by the same afferent volley. This convergence was of particular interest along the parasagittal strip of hindlimb climbing fiber distribution in lobule V. It was not possible to translate the observations into some map of the cerebellar cortex on which are marked the territorial distributions from the various limb afferent nerves. Rather, there was an ill-defined patchy character, closely adjacent Purkyně cells often receiving very different subsets of the total input from the various limb nerves. The unitary integrations accomplished by the individual Purkyně cells are further integrated when their axons converge onto and inhibit the neurones of the cerebellar nuclei, and this integration by convergence would occur in each successive relay on the output pathways from the cerebellum. It is pointed out that the experimental findings on the integrative action of the individual Purkyně cells provide basic information for attempts to construct models simulating cerebellar performance and control. [ABSTRACT FROM AUTHOR]

This paper gives an account of the responses of cerebellar fastigial cells to various afferent inputs from ipsilateral forelimb or hindlimb. Most of the preparations (17 out of 25) have been decerebrate and unanesthetized. The remainder were under anesthesia - chloralose, pentothal or surital. The afferent inputs have been provided by stimulation of predominantly cutaneous limb nerves or by three types of mechanical stimulation: taps to foot pads; pressure on foot pads; air jets to hairy skin. Recording from single fastigial cells was extracellular by glass microelectrodes, and computer averaging techniques of spike responses were employed as described in previous papers. Identification of fastigial cells was simply from location in the large fastigial nucleus, this location being later confirmed by identification of microelectrode tracks in histological sections. Fastigial cells display a fairly steady background discharge, the mean being 37 Hz for the decerebrate and considerably lower for the anesthetized. Pad taps usually evoked a diphasic (excitatory-inhibitory) response, but in some cases the inhibitory was dominant, in others the excitatory. The threshold was below 0.2 mm, and several fastigial cells were excited or inhibited by taps of only 0.01 mm. Air jet stimulation of hairy skin of the foot evoked similar responses. Durations of excitation were usually about 10 msec but inhibition was longer, usually about 50 msec. Nerve stimulation evoked responses of comparable type, but the latency was at least 4 msec shorter, corresponding to the more direct and shorter pathways from the site of stimulation. With some fastigial cells steady pressure to central foot pads of 2 sec duration evoked only brief phasic responses (excitatory or inhibitory) at 'on' and 'off'. With other cells there were tonic responses - excitation or inhibition or admixtures thereof - for the whole duration of the pressure. Usually 500 g was almost maximally effective, and the threshold was always below 100 g. In an indeterminate type of response (the semitonic) the excitation or inhibition at 'on' persisted for up to 500 msec, an effect matching the response of the rapidly adapting receptors of the pads. With repetitive stimulation both the excitatory and inhibitory responses to pad taps were reduced with frequencies above 1 Hz and greatly depressed at 5 to 7 Hz. However a small inhibition was observed to persist during tap frequencies as high as 65 Hz. In a preliminary study both the background and the evoked responses of fastigial cells were found to be very sensitive to barbiturate anesthesia. [ABSTRACT FROM AUTHOR]

This paper gives an account of single mossy fiber responses when three types of mechanical stimulation are applied to the forefoot and hindfoot of the cat which is either decerebrate and unanesthetized or lightly anesthetized by pentothal or chloralose. The mechanical stimuli were applied either to footpads (brief pulses, taps, or longer square pulses or ramps) or to the hairy skin by air jets. Recording of single mossy fibers was extracellular by glass microelectrodes that were inserted into the granular layer of the cerebellar cortex or the subjacent white matter. As described in previous papers computer averaging techniques usually of 64 responses have been employed to enhance reliability. Taps evoked pure excitatory responses from many mossy fibers, which were usually brief high frequency bursts resembling those evoked by nerve volleys. Usually the threshold displacement was less than 0.2 mm and thresholds as low as 0.01 mm were observed. There were often considerable differences in the intensities of responses from different pads of the same foot. Successive pulses of mechanical stimulation evoked mossy fiber responses of diminished intensity. Longer mechanical stimuli with square or ramp onsets evoked various admixtures of phasic and tonic responses. Hair stimulation was often a very effective excitant, the receptive field for a single mossy fiber usually covering a considerable area of foot and leg. Taps and pressure to the pads were also effective in inhibiting the background discharge of some mossy fibers, and admixtures of excitatory and inhibitory actions were observed. The results are discussed in relationship to the discharges evoked in primary afferent fibers by cutaneous mechanoreceptor stimulation. They provide an intermediate stage of information between mechanoreceptor stimulation and the response of Purkyně cells as described in the next paper. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The preceding two papers gave accounts of mossy fiber (MF) or of climbing fiber (CF) inputs to Purkyně cells under conditions where the other input was depressed by the experimental procedure. By utilizing either chloralose anesthesia or decerebration with sparing of the pyramidal tracts it has been possible to study the convergence of MF and CF inputs onto single Purkyně cells. The stimulation of cutaneous mechanoreceptors, the recording procedures for unitary Purkyně cell discharges and the computer averaging techniques were as previously described. Testing by taps to the footpads evoked a combined MF and CF response more commonly than either response alone, and often both inputs were very effective. There was a tendency for such phasic CF responses to be more frequently observed than the tonic responses to pad pressure, but such responses did occur. Purkyně cells were located by the usual procedure along the microelectrode tracks later identified in serial sections. Those cells activated by the fast MF inputs from the pad receptors were found to be closely associated in groups or colonies. The delayed MF inputs probably via spino-reticular pathways were more widely dispersed. The topographical relationships of these colonies are displayed on maps of the unfolded cerebellar cortex for lobules II to VI of both vermis and pars intermedia. In general these distributions of Purkyně cells activated from forefoot and hindfoot appear as islands in the larger fields that degeneration procedures exhibit for the cuneocerebellar and dorsal spinocerebellar tracts respectively. The CF inputs from the footpads also project to these same colonies, so that there are conjoint MF and CF colonies. The several modalities of the cutaneous mechanoreceptors of the forefoot or hindfoot often participate in the receptive fields of individual Purkyně cells. Such a field may be restricted to one or other side of the foot, all tested cutaneous mechanoreceptors then sharing approximately in the same restriction. Finally it is shown how these experimental findings relate to the theories of cerebellar function, particularly to the dynamic loop hypothesis. [ABSTRACT FROM AUTHOR]

This paper is the first of a series in which the processing of information in the cerebellum has been studied by investigating the effects that known inputs from limb nerves produce on the unitary spike potentials in the cerebellar cortex. These spikes have been recorded extracellularly at all depths along microelectrode tracks in the 5th, 4th and 3rd lobules of the anterior lobe in the lateral vermis or in the pars intermedia. These units have a background frequency of discharge, often very irregular, and computer averaging techniques have been employed in order to derive reliable information on the time course and intensity of the excitatory and/or inhibitory actions produced by the input against this background. Most of the spike responses recorded from the granular layer fall into two classes, one characteristic of impulses in mossy fibers, and the other of impulse discharges from granule cells. Both in the spontaneous background and in the response to afferent volleys in limb nerves the mossy fibers exhibit a performance in close accord with that described for the discharges up the spino-cerebellar tracts. The short latency of 6-9 msec for hindlimb stimuli and the high frequency burst response of 2-4 impulses are characteristic. The mossy fibers displayed a wide variety of responses to the wide range of testing inputs, there being various combinations of excitatory and inhibitory responses and also delayed excitatory actions, all of which must be assumed to be reflections of synaptic influences on the cells of origin of the mossy fibers in the spinal cord. Granule cells have a longer latency by several milliseconds, 9-20 msec for the hindlimb, and a slower frequency in their burst response which tended to be longer and more irregular. The small unitary spike potentials are more difficult to isolate. Also with repetitive stimulation granule cells are more readily depressed than are mossy fibers. Usually a granule cell exhibits a wider range of response to the various cutaneous and muscular afferents of a limb. Both mossy fibers and granule cells may display reciprocal responses to volleys from muscle nerves to antagonistic muscles. This attempt to define properties of the mossy fiber and granule cell spike potentials should help in their identification in future investigations. [ABSTRACT FROM AUTHOR]

Unilateral cerebellar lobectomy was carried out in young and mature macaques. There is no significant abnormality in saccadic eye movement or in the vestibulo-ocular reflex. There is a constant drift of the eyes in the contralateral direction, and the abilities to maintain eccentric gaze and to make smooth pursuit movements are jointly affected. The syndrome is transient in young monkeys, and even bilateral cerebellar lobectomy carried out serially leaves some ability to hold eccentric gaze and pursue smoothly. The findings permit the conclusion that the primate oculomotor organization depends on the active maintainence of straight ahead gaze. Saccades move the eyes in a coordinated way, and are also associated with correlated innervation to hold the gaze in the new position. Since cerebellar interventions which cause centripetal drift also always produce defects in pursuit movements, the abilities to maintain eccentric gaze and to pursue smoothly must have a common origin. [ABSTRACT FROM AUTHOR]

The responses of single Purkyně cells in the pars intermedia of the anterior lobe were studied following stimulation of the sensorimotor cortex in the cat. The cortical inputs display the same kind of mossy fiber and climbing fiber duality as previously described for nerve inputs (Eccles et al., 1971 b). Stimulation of the cerebral cortex elicits short latency excitation (4-8 msec) and inhibition (8-12 msec) via the mossy fiber system and a longer latency climbing fiber excitation (12-19 msec). The response of a Purkyně cell may consist of any combination of these possible components and depends upon the cortical area stimulated. The mossy fiber system is activated by a single shock, is increased by a second volley, and follows relatively high repetition rates. On the other hand, the climbing fiber system has a higher threshold, and only follows repetition rates up to 5-20 Hz. Two or more volleys are needed for efficient transmission. [ABSTRACT FROM AUTHOR]

The patterns of convergence of nerve and cortical inputs representing the forelimb and hindlimb were studied in Purkyně cells of the cat. The most important inputs to Purkyně cells of the pars intermedia come from peripheral nerves and the areas of the sensorimotor cortex concerned with the same limb. In lobule V, the forelimb nerve and cortical inputs are dominant, while in lobules III and IV the hindlimb inputs are dominant. Lobules IVa-Va represent a zone of hindlimb-forelimb overlap, with the nerve and cortical inputs making parallel transitions from the hindlimb dominance of IVa to the forelimb dominance of Va. Furthermore, within the nerve and cortical projections to the pars intermedia, mossy fiber and climbing fiber systems have similar projection patterns. In addition to the hindlimb-forelimb overlap in lobules IVa-Va, nearly half (44%) of the Purkyně cells throughout lobules III, IV, and V of the pars intermedia respond with weak or moderate responses to cortical or nerve inputs from the non-dominant limb, some of which are clearly important physiologically. By pairing stimuli to nerve and cortex, it was shown that these two inputs converge onto single inferior olive neurons for the climbing fiber system, whereas the nerve and cortical inputs have separate mossy fiber-granule cell pathways, finally converging onto the Purkyně cell. For both the mossy fiber and climbing fiber systems, the nerve and cortical inputs appear to be transmitted most efficiently through the cerebellar cortex when the two inputs arrive simultaneously at the cerebellar cortex and inferior olive, respectively. [ABSTRACT FROM AUTHOR]

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 Purkyně 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 Purkyně 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. [ABSTRACT FROM AUTHOR]

The organization of the cerebellar, vestibular and spinal inputs to the lateral and medial vestibulospinal tract (LVST and MVST) cells was studied in anaesthetized rabbits. Synaptic actions of these inputs were determined by recording postsynaptic potentials intracellularly and also unit spike discharges extracellularly from a number of LVST and MVST cells. As reported previously in cats, inhibition was evoked very frequently from the vermal cortex of the cerebellar anterior lobe and less frequently from that of the posterior lobe. However, no such inhibition was derived from the flocculus. The cerebellar inhibition was exerted upon both LVST and MVST cells, whether they received monosynaptic activation from the primary vestibular afferents (second-order) or not and whether they conducted impulses fast or slowly. However, the inhibition was frequently absent in 'slow' 'second-order' MVST cells. The vast majority of LVST and MVST cells received an excitatory input from the spinocerebellar afferents ascending the funiculus posterolateralis. This input was particularly prominent from the upper cervical cord. The spinal excitation thus obtained occurred in close connection with the cerebellar inhibition. Hence, it appears that the cerebellar vermis receives the spinal signals that drive LVST and MVST cells and in turn sends out inhibitory signals to adjust the reflex activity in these cells. [ABSTRACT FROM AUTHOR]

In precollicular decerebrate cats, limb nerves have been stimulated and field potentials and unitary activity recorded from the cerebellar cortex. Doses of pentothal up to 8 mg/kg affect neither the activity evoked in the fast mossy fibre pathways, nor the size of the postsynaptic potentials in granule cells, but the axon discharge in these latter cells is clearly affected. With 4-8 mg/kg the axon discharge of granule cells is abolished and as a consequence Purkinje cells do not respond to the peripheral stimulation via the mossy fibres. In contrast the activity evoked through the climbing fibres is enhanced. This effect takes place at precerebellar level. Both the effects on the mossy fibre and climbing fibre pathways show a recovery in 15-60 min depending on the dose. [ABSTRACT FROM AUTHOR]

The effect of isometric contraction of the gastrocnemius-soleus muscle group was investigated on the responses of 79 cerebellar Purkyně cells (P-cells) in the decerebrate cat. Forty three percent of the P-cells tested were responsive to contraction via a pathway that acted by way of climbing fibres. The latency of these responses was long (mean 60 msec following ventral root stimulation) and variable. It was concluded that the responses were attributable to Group Ib afferent input. An excitatory action of the contraction on spindle afferent fibres was excluded because the responses were: a) evoked by submaximal contractions produced by weak single shock stimulation of the ventral root; b) negligible following isotonic contractions; and, c) augmented when a stretch was superimposed on the rising phase of the twitch. The effects of both muscle contraction and muscle vibration were studied for many of the P-cells in order to investigate the convergence from afferents of both spindle and tendon organ origin. Few P-cells had evidence of a convergent input from Group Ia, II, and Ib fibres. In contrast convergence from Group II and Group Ib input was quite common. With some cells, there appeared to be an input from only Group Ib or Group II fibres. [ABSTRACT FROM AUTHOR]

An account is given of single Purkyně cell responses that are evoked by cutaneous mechanoreceptors acting via climbing fibers (CF). There was no complication by mossy fiber input, which was selectively depressed by light pentothal anesthesia. Brief mechanical pulses (taps) to the footpads and air jets on hairy skin were very effective in evoking CF responses, the usual range of latencies being 25-35 msec for the hindfoot and 19-30 msec for the forefoot. There was often a considerable difference in the effectiveness of the different pads of the same foot. For any particular Purkyně cell there was a close correspondence between the receptive fields for footpads and hairy skin. The threshold was often below 0.02 mm taps for the most sensitive pads, and was even lower for more prolonged mechanical displacements. Mechanical pulses of 80 to several hundred msec in duration were effective in evoking CF responses of Purkyně cells at 'off' as well as at 'on.' This finding and the very low threshold strongly suggest Pacinian corpuscles as the principal receptors concerned in activating the CF system. Repetitive taps to footpads were effective at slow frequencies, 5 or 10 Hz, but there was a response only to the first tap with a frequency of 65 Hz. [ABSTRACT FROM AUTHOR]

In cats without general anaesthesia electric stimulation of the optic chiasma evoked usually in the depth of the cerebellar cortex of lobuli VI and VII a sequence of waves at a latency of 7-10 msec which have been shown to be due to the mossy fibre input. A later wave at a latency of 18-20 msec was also sometimes found in isolation or in association with the early wave. This later field has been identified as due to the climbing fibre input. Unitary recordings have given support to this interpretation. Some correlation has been made with recordings obtained by electric stimulation of the superior colliculus and by flash stimulation of the retinae. It is concluded that the optic pathways project to the visual area of the cerebellar cortex through both mossy and climbing fibre inputs, although from this study based mainly on the laminar analysis of evoked fields, the former input seems to be more widespread and more consistently obtained than the latter. [ABSTRACT FROM AUTHOR]

Investigations were made in the decerebrate cat of the effect of muscle vibration on the activity of 342 Purkyně cells in the ipsilateral anterior lobe of the cerebellum. The effects were studied for three different muscle groups: in the hindlimb, the anterior tibial group (extensor digitorum longus, peroneus longus, brevis and tertius, and tibialis anterior) and gastrocnemius-soleus; and in the forelimb, the extensor digitorum lateralis and communis muscles. The responses of Purkyně cells were mediated by both the mossy fibre and climbing fibre inputs. The mossy fibre induced responses were generally inhibitory and had latencies only a few msec longer than responses evoked by stimulation of the nerve supplying the muscle. In contrast, the latencies of responses mediated by the climbing fibres were long and variable. Nine cells out of 342 Purkyně cells showed weak response to vibration of less than 60 μ amplitude, as compared to approximately 40% of those which responded to vibration of above 60 μ up to 200 μ amplitude, indicating the preponderant action of Group II afferents on the Purkyně cells in contrast to far less influence from Group Ia afferents. There was no obvious difference in threshold of vibration amplitude regarding the response mediated by the climbing or mossy fibres. Purkyně cell responses mediated by both mossy and climbing fibre inputs displayed temporal summation in response to muscle vibration, although no tonic effects were observed in response to maintained periods (1-5 sec) of vibration. Purkyně cell responses evoked by the mossy fibre input were unable to follow the individual cycles of vibration at frequencies above approximately 50 cps. Those evoked by the climbing fibres could follow at frequencies of less than 10 cps. [ABSTRACT FROM AUTHOR]

Stimulation of the parallel fibres, or the mossy fibres, in the cerebellar cortex depresses the potential generated in the granular layer by anti-dromic invasion of the Purkinje cells (N), and that generated by the axon discharge of granule cells (P). The reduction of these potentials indicate inhibitions mediated respectively by basket and Golgi cells. The depressions of both N and P potentials are unaffected by strychnine at doses of up to 1 mg/kg. Picrotoxin and bicuculline reduce or suppress both inhibitions at doses of 2 to 5 mg/kg and 0.2 to 0.4 mg/kg respectively. The action of the picrotoxin is long lasting or even possibly irreversible, whereas that of bicuculline lasts only a few minutes. The ratio by weight between the dose of picrotoxin and that of bicuculline necessary to reduce the N and P depression exceeds 10. These results indicate that gamma-aminobutyric acid may be the chemical inhibitory transmitter at basket cell - Purkinje cell and Golgi cell - granule cell synapses. [ABSTRACT FROM AUTHOR]

Impulses discharged by Purkyně cells provide the only output from the cerebellar cortex. Usually the Purkyně cells can be identified with certainty because they alone respond by the brief bursting discharge generated by climbing fiber (CF) impulses, as well as by the ubiquitous simple spikes. The discharges from single Purkyně cells in the anterior lobe have been studied in lightly anesthetized and in decerebrate unanesthetized cats. All of our 275 identified cells had an average background discharge frequency in the range of 5/sec to 100/sec. The discharge was increased and/or depressed by afferent volleys from a number of limb nerves. In addition there was usually a slow rate of CF-evoked spike bursts at 0.5-2/sec, and many afferent inputs also evoked CF responses. The firing patterns of Purkyně cells are often very irregular, but by the technique of computer averaging of many sweeps, usually 128, the responses of the cell under observation have been accurately and reliably displayed as post-stimulus time histograms and their cumulative frequency distributions. In this manner the distinctive features of the responses evoked by the mossy fiber and climbing fiber inputs have been determined under a wide variety of conditions. The most direct mossy fiber responses - excitatory or inhibitory - had a shorter latency than the climbing fiber responses, usually by more than 10 msec. However, there were also later responses to both types of input. Repetitive afferent volleys were used to study facilitation of the mossy fiber responses at short intervals, and the effectiveness of repetition on both kinds of inputs at slower frequencies. Repetitive mossy fiber inputs apparently can give a maintained enhancement or depression of the Purkyně cell discharge. [ABSTRACT FROM AUTHOR]

The distribution of degenerating fibres in the nucleus reticularis tegmenti pontis (N.r.t.) has been examined in Nauta (1957) impregnated sections from cats with discrete lesions of various cortical regions. The following cortical regions send fibres to the N.r.t.: Ms I, Sm I, Sm II, the orbital gyrus, the proreate gyrus, the parietal cortex and parts of the medial surface of the frontal lobe. The projection is bilateral, but mainly ipsilateral. The main terminal area of fibres from all cortical regions mentioned is the ventral part of the N.r.t. at middle rostrocaudal levels. Within this territory most cortical regions have their particular terminal sites in the N.r.t., but there is considerable overlapping. The anatomical organization and the role of the N.r.t. as a cerebrocerebellar relay station are discussed. The regions of the N.r.t. not receiving cortical fibres are supplied by fibres from other sources. These fibre groups have their preferential, although overlapping, areas of termination. In its organization the N.r.t. differs markedly from the pontine nuclei proper. Like the two other precerebellar reticular nuclei the N.r.t. appears to provide possibilities for an integration of impulses from the cerebral cortex with those from many other sources before they influence the cerebellum. [ABSTRACT FROM AUTHOR]

The influence of the cerebellum on the activity of Deiters' cells has been studied by comparing the extracellularly recorded activity of single cells in decerebellate cats and in those with an intact cerebellum. The tonic inhibitory influence of the cerebellum is reflected in three ways: a smaller proportion of those cells projecting to the spinal cord is spontaneously active; fewer cells are found which do not project to the spinal cord, indicating that activity in this population of cells is depressed; among those cells that are spontaneously active, the rates of discharge are lower. In the decerebellate cat, stimulation of either ipsior contralateral limb nerves facilitates many cells, whereas in the presence of the cerebellum, peripheral stimulation evokes facilitation followed by inhibition. The inhibition is ascribed to activation by peripheral stimulation of Purkinje cells projecting to Deiters' nucleus from the cerebellum. The thresholds for facilitation and inhibition are similar but longer stimulus trains are required to evoke inhibition. Inputs from many different nerves converge upon the same cell. Among the nerves to muscles, quadriceps was the only nerve effective at stimulus strengths below the group III range. Three populations of cells are found in Deiters' nucleus: cells receiving somatic inputs but not labyrinthine inputs; cells receiving inputs from both the labyrinth and ascending somatic systems; cells activated from the labyrinth but free of somatic influences. [ABSTRACT FROM AUTHOR]

The effect of stimulation of the Entopeduncular nucleus on the thalamic ventrolateral nucleus (VL) was studied by recording with macroelectrodes and microelectrodes in cats anesthetized with chloralose or under local analgesia. An asynaptic response (0.5 ms shortest latency) was evoked in the VL following the Entopeduncular stimulation. It is demonstrated that this response is attributable to the activation of the Entopeduncular-VL fibers described by anatomists. The postsynaptic events revealed, since only a small proportion of VL cells are affected by Entopeduncular stimulation, that the influence exerted by the Entopeduncular nucleus on the VL is much weaker than the cerebellar one. [ABSTRACT FROM AUTHOR]

Excitatory synapses in the rat cerebellar cortex contain large, spheroid vesicles and inhibitory synapses contain small, ovoid vesicles. Presynaptic terminals can be characterized by the ratio of spheroid: ovoid vesicles (Q-value). Neither the inhibition of acetylcholine synthesis by hemicholinium, nor the inhibition of GABA synthesis by thiosemicarbazide, does induce any significant alterations in the Q values. It is suggested that synaptic vesicles bind mediator substances on their surface membranes. [ABSTRACT FROM AUTHOR]

Volleys in group I and II fibers of muscle nerves and group II fibers of cutaneous, joint and fascial nerves have evoked CF responses in the anterior lobe of the cerebellum. In the pars intermedia there is a fairly sharp somatotopic localization of the forelimb CF responses to the Vth lobule (Larsell) and the hindlimb to the IVth and IIIrd lobules. In the vermis there is much more admixture, with the hindlimb-evoked responses tending to dominate in the lateral vermis of the Vth lobule, and the forelimb more medially. In the IVth and IIIrd lobules forelimb responses were rare and were never large. In the medial vermis up to 1-1.7 mm from the midline there were no CF-evoked responses from the limb nerves. These distributions of CF-evoked responses are remarkably different from those reported by Oscarsson, and consideration is given to the factors responsible for this discrepancy. A more detailed examination was made of the CF-evoked responses from a large variety of hindlimb and forelimb nerves. Observations were made along many tracks usually arranged in a transverse plane, and it was found that between different recording sites along the same track or along adjacent tracks, there was a great deal of variation in the relative magnitudes of the CF-evoked responses from the different nerves. These distributions have an ill-defined patchy character so that at any focus there is opportunity for the most diverse kinds of piecemeal integration. These findings on the CF-input are considered in relationship to the mossy fiber input. It is pointed out that the pathways conveying CF-input to the cerebellum have a level of discriminative input adequate for the operation of fine control. [ABSTRACT FROM AUTHOR]

Responses were evoked in the anterior lobe of the cerebellum by volleys in group I and II fibers of forelimb and hindlimb nerves - cutaneous, muscular, joint and fascial. These responses have been observed along microelectrode tracks that traverse the whole depth of the anterior lobe. These tracks have been identified in histological sections, and the recording sites along these tracks have been determined. It has been shown that there are many distinguishing features for the responses produced by the two types of afferent input to the cerebellum: climbing fibers and mossy fibers. The depth profiles are of particular importance in the differentiation of the CF and MF responses, and they correspond to those already determined for the exposed surface areas of the cerebellar cortex. As would be expected from the distribution of synapses by the CF fibers to the Purkinje cell dendrites, there is a maximum extracellular negativity deep in the molecular layer with sources superficial and deep thereto. In contrast, the mossy fiber input produces a powerful synaptic excitation in the granular layer, which is recorded there as a negative wave (N). The mossy fiber input by sequential relay also produces a negative wave (N) in the molecular layer. This wave is distinguished from the CF-evoked negative wave because it is not reversed in the fissura and the adjacent superficial molecular layer. An important distinguishing feature of the MF- and CF-evoked responses is that the latencies of the former are shorter by 6-12 msec for forelimb nerves and by 9-15 msec for hindlimb nerves. It is thus possible to measure the sizes of the MF and CF responses in the same traces. Another distinguishing feature is the failure of the CF responses with stimulus frequencies of 5-15/sec, whereas the MF-evoked potentials are well maintained above 15/sec. Also CF-evoked responses show much more size and latency variance than the MF-evoked responses, and often the facilitation of two or three volleys is required in order to evoke a stable CF response. By utilizing these various tests it is always possible to distinguish between the CF- and the MF-evoked responses recorded along the microelectrode tracks in the anterior lobe. [ABSTRACT FROM AUTHOR]

Stimulation of forelimb and hindlimb areas of the sensorimotor cortex in the cat evokes in the lobus anterior of the cerebellum an early response at latency of 3-3.5 msec due to the mossy fibre input (MF) and a later response at latency of 13-16 msec due to the climbing fibre (CF) input. In the pars intermedia these two types of responses are organized in a somatotopic manner: the hindlimb area projects in lobuli HIV and HIII whereas the forelimb area projects to lobulus HV. In the vermis a somatotopic arrangement is less clear. Both forelimb and hindlimb areas of the sensorimotor cortex project to lobuli III, IV and V: on a maintained somatotopy in a caudo-rostral direction there is a tendency for the hindlimb area of the sensorimotor cortex to be well represented in a longitudinal strip close to the paravermal sulcus. This arrangement in the vermis is evident for the CF pathways, but more difficult to demonstrate for the MF pathways. The forelimb area of the sensorimotor cortex projects to those areas of the lobus anterior impinged upon by the forelimb nerves through both the MF and CF systems and the same holds true for the hindlimb area and the hindlimb nerves. [ABSTRACT FROM AUTHOR]

Following the stimulation of cerebellar cortex, a slow depolarization developed in the neurones which were impaled with microelectrodes in the dorsal portion of the nucleus of Deiters. Characteristically, it was produced bilaterally from a wide area of the culmen and, with double shock stimulation at brief intervals, showed a marked potentiation, often in association with a later depression. After repetitive stimulation of the cerebellar cortex the slow depolarization was prolonged for a period of many seconds. Even stimulation of the spinal cord caused similar depolarization. By intracellular injection of currents and ions, the depolarization was shown to be disinhibition, i. e., removal of background inhibition. Accordingly, it was confirmed that there was a steady production of IPSPs in dorsal Deiters neurones, which diminished during the phase of disinhibition. As the possible source of these background IPSPs, the Purkinje cell axons within the nucleus of Deiters were found to be discharging rhythmically at a rate of 20-90/sec, and in fact they were depressed very effectively after cerebellar stimulation. At the same time, volleys along Purkinje cell axons produced by a testing cerebellar stimulation also were diminished, indicating a depression in the excitability of Purkinje cells. [ABSTRACT FROM AUTHOR]

Fractionation of the cat cerebellum has revealed that the parallel fibers of the cerebellar cortex break into two types of fragments which can be recognized in thin sections and in suspensions of negatively stained material. Fragmented material correlates well with electron micrographs of parallel fibers in situ. Parallel fiber axons and their bulbous presynaptic expansions sediment mainly into two subfractions. One unique layer consists of the intersynaptic tubular pieces of parallel fiber axons. Another layer is enriched in the synaptic portions which make contact with Purkinje spines. The possible contaminants of these fractions are discussed. These fractions may permit analysis of the chemical organization of conducting vis à vis synaptic membranes from a known anatomical source. This material was presented as a preliminary report at the Sixth Annual Meeting of the American Society for Cell Biology, November 1966, and is contained in J. Cell. Biol. 31, 52A, 1966. [ABSTRACT FROM AUTHOR]

By recording intracellularly from Deiters neurones of cats, there was a survey of those cerebellar areas that, when stimulated, produced inhibitory postsynaptic potentials (IPSPs) monosynaptically in Deiters neurones. The monosynaptic inhibitory area expanded longitudinally mainly along the ipsilateral vermal cortex of the anterior lobe. The ipsilateral cortex of the posterior lobe was also effective in inhibiting Deiters neurones though less prominently than the anterior lobe. The inhibitory fibers could be stimulated in the white matter of the cerebellum, predominantly in the ipsilateral side at rostral regions of nuclei fastigii and interpositus. It was further shown that the monosynaptic inhibition from the anterior and posterior lobes occurs chiefly in the dorsal portion of Deiters nucleus. Since in both the cerebellum and Deiters nucleus the spatial pattern of distribution of the inhibitory fibers conforms to that of the corticovestibular fibers as histologically defined, the experimental findings are in accord with the hypothesis that the cerebellar Purkinje cells are inhibitory in nature. [ABSTRACT FROM AUTHOR]

Small lesions were done in various areas of the nucleus interpositus anterior (NIA) of the cerebellum, and the distribution of terminal degeneration was studied in the red nucleus with the methods of Nauta and Glees. The NIA projects to the contralateral red nucleus. Two principles of organization can be demonstrated in the projection: a caudorostral arrangement in the red nucleus corresponds to a mediolateral organization in the NIA and a mediolateral arrangement in the red nucleus corresponds to a caudorostral organization of the NIA. The latter distribution coincides with the somatotopical areas of the red nucleus defined by Pompeiano and Brodal (1957). Special attention has been paid to the questions of the subdivision of the cerebellar nuclei and of the course of the fibres issuing from the nuclei in the cerebellar hilus. The present findings on the projection of the NIA to the red nucleus have been correlated with recent anatomical and physiological data on the cerebellum and the red nucleus. [ABSTRACT FROM AUTHOR]

Mass discharges were recorded from the dissected left restiform body in unanaesthetized, decerebrate, and decerebellate cats. The spinal cord was severed in the thoracic or cervical region sparing only the left ventral quadrant. In this preparation the discharges were shown to relate largely or exclusively to activity in the reticulocerebellar tract originating from the lateral reticular nucleus. The ascending spinal tract was identified with the bilateral ventral flexor reflex tract (bVFRT) of Lundberg and Oscarsson (1962). The reticulocerebellar tract was activated from the flexor reflex afferents and nerve volleys from each of the four limbs were equally effective. It is concluded that the lateral reticular nucleus is not responsible for the somatotopically organized projection of cutaneous afferents, as assumed before. The bVFRT is strongly influenced from the cerebellar cortex and the organization of the closed loop formed between the cortex and the spinal cord is discussed. [ABSTRACT FROM AUTHOR]

The experiments were done on unanaesthetized, decerebrate, and decerebellate cats. Recording was made from axons originating in the lateral reticular nucleus on stimulation of various nerves, cutaneous receptors, and certain descending tracts. Excitatory and inhibitory effects were evoked from the flexor reflex afferents of receptive fields which included most of the body surface. It is concluded that the lateral reticular nucleus with respect to its afferent inflow is similar to the non-cerebellar nuclei of the reticular formation. The possibility that the reticulocerebellar tract is important in determining the background excitation of cortical neurones is discussed. The effects evoked by stimulation of descending tracts were consistent with the disclosure that the bilateral ventral flexor reflex tract is the afferent path to the lateral reticular nucleus. [ABSTRACT FROM AUTHOR]

The discharges were recorded from the dissected right restiform body in unanaesthetized, decerebrate, and decerebellate cats. The spinal cord was severed in the thoracic and/or cervical region sparing only the left ventral quadrant. The discharges were shown to relate largely or exclusively to activity in the olivocerebellar tract. The olivocerebellar discharges were elicited by stimulation of the flexor reflex afferents. Large responses were evoked from the right hindlimb nerves and small responses from the left hindlimb nerves. The responses had a latency of about 20 msec. The spinoolivary tract is tentatively identified with the contralateral ventral flexor reflex tract of Lundberg and Oscarsson (1962). [ABSTRACT FROM AUTHOR]

An attempt is made to identify, under the electron microscope, the climbing fibers of the cerebellum (in the cat) and their synaptic contacts with Purkinje cells and other cortical neurons. - Two kinds of axonal profiles, having synaptic contacts with primary and secondary dendrites of Purkinje neurons, can be recognized: One being terminal fibers densely packed with neurofilaments, having mainly contacts 'de passage' with the dendrite surface, with small accumulations of synaptic vesicles at the presynaptic side of the contact. The others are rather knob-shaped contacts filled with synaptic vesicles and poor in neurofilaments. In chronically isolated folia, in which only local neurons and their processes have survived, all filamentous profiles have disappeared while vesicular ones are not appreciably reduced in number. It is inferred from this, that the neurofilamentous profiles correspond to climbing fibers, whereas the vesicular ones could be the endings of outer stellate axons, recurrent Purkinje axon collaterals, or ascending basket axon collaterals. - Similar two kinds of axon-terminal profiles are found in synaptic contact with Golgi and basket cell bodies. As in chronically isolated folia only the vesicular profiles survive, it is inferred that the climbing fiber has axo-somatic terminals on Golgi cells and basket cells as well. Previous information of this kind, gained with the light microscope and with degeneration studies, is thus substantiated with the aid of the electron microscope. The vesicular presynaptic profiles on Golgi and basket neurons are in the first case certainly and in the second with high probability endings of recurrent Purkinje axon collaterals. - The few axosomatic synapses found on outer stellate neurons may also be terminals of climbing fibers, but degeneration evidence for this is not conclusive. - The observations are summarized and evaluated from the functional point of view in a diagram, with consideration to recent physiological information on the function of climbing fibers. [ABSTRACT FROM AUTHOR]