D M Armstrong

Complex spikes in Purkinje cells in the lateral vermis (b zone) of the cat cerebellum during locomotion.

1. Complex spikes (c.s.s) due to climbing fibre input were recorded from forty‐one Purkinje cells in the lateral part of the vermis (i.e. the b zone) of lobule V of the cerebellum in cats walking on a moving belt or a horizontal ladder. Most cells were near the tips of the folia making up the lobule and some were shown by antidromic invasion to project to the ipsilateral lateral vestibular nucleus. In all cells c.s.s. could be evoked through mechanical stimuli delivered manually to the neck and/or trunk and/or the limb girdles and/or the proximal parts of the limbs. 2. During walking c.s.s. occurred at rates which ranged in different cells from 0.8 to 2.55/s (i.e. ca. 0.8 to 2/step). When activity was averaged across many successive steps the probability of c.s. occurrence was never completely constant throughout the step cycle, but no tendency was detected for c.s.s to recur at any precisely fixed time during the cycle. 3. When ladder locomotion was perturbed because a rung underwent an unexpected 2 cm descent when stepped on, some cells generated a c.s. at short latency in a proportion of trials. Such responses were well time‐locked to the onset of rung movement but not to its cessation (which they often preceded). 4. For perturbations of either forelimb the earliest displacement‐related c.s. occurred in different cells between 40 and 64 ms after the onset of rung movement. In different cells c.s.s occurred in from one out of five to three out of four perturbed steps (mean ca. two out of five steps). Eight out of seventeen cells responded to perturbation of the forelimb ipsilateral to the cell and five out of ten responded to contralateral perturbations. 5. Perturbation of the ipsilateral hind limb was accompanied by c.s.s in four out of nine cells and latency was usually longer (by ca. 30‐40 ms). One cell showed a decrease in the probability of c.s. occurrence. Insufficient data were obtained for a systematic study of responsiveness to perturbation of the contralateral hind limb. 6. Cells showed different patterns of limb specificity, responding to perturbation of one, two or all of the three limbs studied. In total, c.s.s accompanied perturbation of at least one limb in thirteen out of twenty cells studied (65%).(ABSTRACT TRUNCATED AT 400 WORDS)

Complex spikes in Purkinje cells of the paravermal part of the anterior lobe of the cat cerebellum during locomotion.

1. The temporal pattern of the discharge of complex spikes by Purkinje cells in the paravermal cortex of the cerebellar lobule V b/c has been examined during locomotion in awake cats. 2. The peripheral receptive fields of 138 Purkinje cells were examined using light tactile stimulation. In 91% of these cells, complex spikes were evoked by stimuli applied to the ipsilateral forelimb and of eighty‐eight cells examined in most detail, 76% had receptive fields including the paw or wrist. Sixty‐six per cent had receptive fields restricted to the paw and/or wrist. 3. Complex spikes were not discharged at rigidly fixed times during the step cycle in any of sixty‐nine Purkinje cells which were recorded during locomotion on a moving belt. 4. When the discharges were averaged over many steps the probability of occurrence of complex spikes showed small fluctuations during the course of the step cycle, but these fluctuations were shown not to be statistically significantly different from those which could arise by chance. 5. These findings are inconsistent with previous suggestions (e.g. Armstrong, 1974; Rushmer, Roberts & Augter, 1976) that, during locomotion, the climbing fibres act to signal the occurrence of specific peripheral events, such as foot touch‐down or lift‐off.

Discharges of nucleus interpositus neurones during locomotion in the cat.

Extracellular recordings were made from ninety‐five cerebellar nuclear neurones in the cat. All were studied during periods of steady walking at 0.5 m/s and most were also studied in the resting animal. Most neurones were in nucleus interpositus anterior; forty‐four cells were shown by antidromic invasion to project to the mid‐brain. Most neurones discharged tonically in the absence of overt movements and the mean rate was 42 impulses/s (S.D. +/‐ 23). During locomotion the mean rate was 68 impulses/s (S.D. +/‐ 32). In all but seven neurones the discharge during locomotion was frequency modulated but in different neurones the depth of modulation varied from 5 to 161 impulses/s (mean 52 impulses/s; S.D. +/‐ 30) and the time of peak discharge relative to the step cycle in the ipsilateral forelimb also varied widely. Despite the individual differences the population as a whole was much more active during forelimb swing than during stance, both in numbers of neurones strongly active and in over‐all average discharge rate (74 impulses/s as compared with 55). Most neurones had tactile receptive fields on the ipsilateral forelimb while others received input from head and neck or from both ipsilateral limbs. The tendency to discharge preferentially during early swing was greatest for the first group, especially the subpopulations with receptive fields around or proximal to the elbow. Cells encountered in close sequence during a micro‐electrode track had similarly located receptive fields and usually showed similar patterns of discharge during locomotion. These findings are discussed in relation to the suggestion by Orlovsky (1972a, b, c) that nucleus interpositus assists in regulating locomotion by evoking rubrospinal discharges which facilitate the flexor muscle activities produced by the spinal mechanisms responsible for generating the swing phase of the step cycle.

Neuronal activity in the lateral cerebellum of the cat related to visual stimuli at rest, visually guided step modification, and saccadic eye movements

1 The discharge patterns of 166 lateral cerebellar neurones were studied in cats at rest and during visually guided stepping on a horizontal circular ladder. A hundred and twelve cells were tested against one or both of two visual stimuli: a brief full‐field flash of light delivered during eating or rest, and a rung which moved up as the cat approached. Forty‐five cells (40 %) gave a short latency response to one or both of these stimuli. These visually responsive neurones were found in hemispheral cortex (rather than paravermal) and the lateral cerebellar nucleus (rather than nucleus interpositus). 2 Thirty‐seven cells (of 103 tested, 36 %) responded to flash. The cortical visual response (mean onset latency 38 ms) was usually an increase in Purkinje cell discharge rate, of around 50 impulses s−1 and representing 1 or 2 additional spikes per trial (1.6 on average). The nuclear response to flash (mean onset latency 27 ms) was usually an increased discharge rate which was shorter lived and converted rapidly to a depression of discharge or return to control levels, so that there were on average only an additional 0.6 spikes per trial. A straightforward explanation of the difference between the cortical and nuclear response would be that the increased inhibitory Purkinje cell output cuts short the nuclear response. 3 A higher proportion of cells responded to rung movement, sixteen of twenty‐five tested (64 %). Again most responded with increased discharge, which had longer latency than the flash response (first change in dentate output ca 60 ms after start of movement) and longer duration. Peak frequency changes were twice the size of those in response to flash, at 100 impulses s−1 on average and additional spikes per trial were correspondingly 3–4 times higher. Both cortical and nuclear responses were context dependent, being larger when the rung moved when the cat was closer than further away. 4 A quarter of cells (20 of 84 tested, 24 %) modulated their activity in advance of saccades, increasing their discharge rate. Four‐fifths of these were non‐reciprocally directionally selective. Saccade‐related neurones were usually susceptible to other influences, i.e. their activity was not wholly explicable in terms of saccade parameters. 5 Substantial numbers of visually responsive neurones also discharged in relation to stepping movements while other visually responsive neurones discharged in advance of saccadic eye movements. And more than half the cells tested were active in relation both to eye movements and to stepping movements. These combinations of properties qualify even individual cerebellar neurones to participate in the co‐ordination of visually guided eye and limb movements.

Discharges of interpositus and Purkinje cells of the cat cerebellum during locomotion under different conditions.

1. Extracellular microelectrodes were used in free‐to‐move cats to study the locomotor‐related discharges of Purkinje cells in the intermediate part of lobule V of the cerebellar anterior lobe and of neurones in the underlying nucleus interpositus anterior. All cells studied discharged rhythmically during locomotion. 2. The discharges during walking at a speed of 0.5 m/s on a horizontal exercise belt were compared with those during (a) walking at 0.9 m/s (when the duration of the step cycle is shortened considerably and the amplitudes of the locomotor electromyograms (EMGs) recorded from flexor and extensor muscles of the limbs are markedly increased) and (b) during walking at 0.5 m/s with the belt tilted uphill by 30 deg (when step duration is little changed but locomotor EMGs are increased by 70‐100%). 3. In each of thirty Purkinje cells the timing of the discharges relative to the forelimb step cycle showed no major difference between the two speeds of walking. Most cells discharged at slightly higher overall rates at the faster walking speed but the increase was usually modest, the average being only 5.6 impulses/s (i.e. an increase of 8%). Peak rates sometimes underwent larger increases but the average was only 11.9 impulses/s (+11%). Changes in minimum rate were generally small (an average increase of 0.3 impulses/s). 4. Among twenty‐one interpositus neurones there was only one in which discharge timing relative to the step cycle was different between the two speeds. Like the Purkinje cells, most neurones discharged slightly faster at the higher speed but the average increase was only 5.5 impulses/s (+8.5%). Peak firing rates also usually showed a modest increase (averaging 6.2 impulses/s; +6.5%) while minimum rates were little changed. 5. Among nineteen Purkinje cells compared between walking uphill and on the flat only one showed any major difference in discharge phasing; overall firing rates were on average only 1.3 impulses/s (2%) higher for uphill locomotion. 6. Among twenty‐one interpositus neurones discharge phasing differed markedly between walking uphill and on the flat in only two cells. Overall discharge rates were on average slightly higher uphill (by 3.5 impulses/s; 6.7%) and peak rates also usually increased slightly (on average, by 6 impulses/s; 7.7%). Minimum rates were higher, on average, by 1.6 impulses/s (+5%). 7. The findings are discussed in relation to current notions of how the intermediate part of the cerebellum may contribute to movement control and it is concluded that the neurones studies probably make little contribution to determining the vigour of the movements of steady walking.

Changes in the discharge patterns of cat motor cortex neurones during unexpected perturbations of on-going locomotion.

1. The impulse activity of single neurones in the forelimb part of the motor cortex was recorded extracellularly in unrestrained cats during self‐paced locomotion on a horizontal circular ladder. 2. Fifty‐one cells (forty‐nine of which discharged rhythmically in time with the step cycle) were recorded during encounters with a number of rungs that could be locked firmly in position or, alternatively, held in position by weak springs so that when stepped on they unexpectedly descended (under the weight of the animal) from 1 to 5 cm before contacting a mechanical stop. 3. In eleven cells (22%) including four fast‐axon pyramidal tract neurones (PTNs), an increase in discharge occurred when the contralateral forelimb descended unexpectedly. Onset latency relative to the start of rung movement ranged from ca 20 to ca 100 ms. In eight cells latency was such that most of the response preceded contact of the rung with the stop; averaged over a number of trials the altered discharge in five of these cells (including two PTNs) represented an accurate profile of the averaged velocity of rung (and foot) descent. The three remaining cells appeared to be responding largely to the cessation of rung movement. 4. Thirty‐six of the cells were also studied during unexpected descent of the ipsilateral forelimb and six (17%) displayed an increase in discharge (onset latency ca 35 to ca 80 ms); three of these were among those that also responded to contralateral descents. 5. These findings for skilled locomotion requiring a high degree of visuomotor coordination are discussed and it is concluded that the motor cortex is rapidly informed regarding unexpected perturbations delivered to the contralateral forelimb at the onset of stance and that changes are evoked in the pattern of impulse traffic descending via the pyramidal tract.

Step phase-related excitability changes in spino-olivocerebellar paths to the c1 and c3 zones in cat cerebellum.

1. Chronically implanted microwires were used to record extracellular field potentials generated in the c1 and c3 zones in the cortex of lobules V and VI of the cerebellum by non‐noxious stimuli delivered to the superficial radial nerve in the ipsilateral forelimb. Responses due to input via climbing fibre afferents were studied; their latency and other characteristics identified them as mediated mainly via the dorsal funiculus spino‐olivocerebellar path (DF‐SOCP). 2. Responses at individual sites were studied repeatedly with a range of stimulus intensities and during two different behaviours: quiet rest and steady walking on an exercise belt. For responses during walking, step histograms were constructed showing response mean size during different tenths of the step cycle in the ipsilateral forelimb, both in absolute terms and relative to mean size during rest. 3. Step histograms for the same site on different days or different stimulus intensities varied appreciably in form but in both cases the timing of the largest response was usually the same or shifted by only one step tenth. 4. In both zones the largest responses during walking occurred overwhelmingly during the E1 step phase when the limb is extended forwards and down to establish footfall. Least responses were much less uniform in timing but were mostly during stance, particularly its early (E2) part. 5. In many histograms the smallest responses were smaller in mean size than the responses during rest while the largest were larger. These changes were not paralleled by changes in nerve volley size, so presumably reflect step‐related central changes in pathway excitability. Facilitations and depressions were differently affected by stimulus intensity and sometimes occurred independently, suggesting generation by separate mechanisms. 6. In both zones there were differences between recording sites which suggests that different DF‐SOCP subcomponents innervate different parts of the zones. However, no systematic differences could be firmly established between the medial and lateral subzones of the c1 zone. 7. The results are discussed in relation to the hypothesis that the DF‐SOCP constitutes the afferent limb of a transcerebellar mechanism involved in adapting the evolving step.

Chapter 23 Aspects of cerebellar function in relation to locomotor movements

Publisher Summary This chapter focuses on two aspects of cerebellar function. The first is the role(s) of the spinoolivocerebellar pathways, which terminate as climbing fibres and feature prominently among the numerous paths that convey the information to the cerebellum from sensory receptors in the limbs. The second aspect is the likelihood that the cerebellar hemisphere is involved in the predictive control of movements, when visual information is used by the central nervous system to bring about anticipatory adaptive adjustments to the motor output. Most of the studies have been carried out in cats trained to walk steadily so as to maintain constant position on a motor-driven exercise belt moving at a comfortable walking speed of c. 0.5 ms –1 , but more recently, the recordings have also been made in cats walking on the rungs of a horizontal ladder to obtain a food reward. Although the study of cerebellar responses to perturbations and anticipatory adaptations of the movements of walking in the cat is as yet in its infancy and lags behind the study of similar responses in the context of reaching and manipulative movements of the monkey forelimb, sufficient has been achieved to indicate that locomotor paradigms will be of considerable utility in the task of seeking to understand the contributions of different regions of the cerebellum to the central nervous control of movements.

Locomotion-related variations in excitability of spino-olivocerebellar paths to cat cerebellar cortical c2 zone.

1. Cutaneous nerve stimulation was used to study the excitability of the spino‐olivocerebellar pathways (SOCPs) to the c2 zone of the paravermal cerebellar cortex in the cat. Non‐noxious single‐shock stimulation of the right and left superficial radial (SR) nerves via implanted cuff electrodes was used to evoke field potentials in the cerebellar cortex via the SOCPs. 2. The evoked potentials were recorded extracellularly either in lobule V of the anterior lobe (three cats) or within the paramedian lobule of the posterior lobe (one cat) with glass‐coated tungsten microelectrodes. Measurement of the amplitudes of the responses was used to monitor transmission in the SOCPs in cats at rest and during walking. 3. A total of eleven c2 recording sites were investigated in detail. At seven of these sites, responses were recorded both during locomotion and at rest. For all seven sites responses during locomotion were smaller, more variable in amplitude and less securely evoked (average reduction 59%). 4. At five out of the eleven recording sites (45%) the mean amplitude of responses elicited during different tenths of the step cycle fluctuated sufficiently that the largest response was more than twice the smallest. In the majority of these cases (4/5) the responses were largest in either mid‐stance or late swing. These fluctuations in response size occurred without parallel fluctuation in the amplitude of the peripheral nerve volley. At the remaining sites fluctuation of the cerebellar field size was less and in some cases practically absent. 5. At six recording sites it was possible to record the climbing fibre potentials evoked by stimulation of both the ipsilateral and contralateral superficial radial nerves. In all six cases the fluctuations in size of the response during locomotion occurred in phase, despite the fact that the two limbs move out of phase. 6. The probability that an individual stimulus would evoke any cerebellar response also varied between the different tenths of the step cycle and such variations occurred in parallel with the fluctuations in response size. This shows that the SOCP regulatory mechanism(s) must, at least in part, operate at a precerebellar level.

Central regulation of motor cortex neuronal responses to forelimb nerve inputs during precision walking in the cat.

1 The responses of neurones in forelimb motor cortex to impulse volleys evoked by single pulse electrical stimulation (at 1.5 or 2 times the threshold for most excitable nerve fibres) of the superficial radial (SR) and ulnar (UL) nerves of the contralateral forelimb were studied in awake cats both resting quietly and walking on a horizontal ladder. Nerve volley amplitude was monitored by recording the compound action potential elicited by the stimulus. 2 In the resting animal 34/82 (41 %) cells yielded statistically significant responses to SR stimulation, and 20/72 (28 %) responded to UL stimulation. Some responses were confined to or began with an increase in firing probability (‘excitatory’ responses) and others with a decrease in firing (‘inhibitory’ responses), typically including a brief interruption of the spike train (zero rate). Cells responding to both nerves usually yielded responses similar in type. Most (78 %) response onset latencies were less than 30 ms. Responses involved the addition or subtraction of from 3.4 to 0.1 impulses stimulus−1 (most < 1 impulse stimulus−1). The distribution of response sizes was continuous down to the smallest values, i.e. there was no ‘gap’ which would represent a clear separation into ‘responsive’ and ‘unresponsive’ categories. Responses were commonest in the lateral part of the pericruciate cortex, and commoner among pyramidal tract neurones (PTNs) than non‐PTNs. 3 During ladder walking most cells generated a rhythmic step‐related discharge; in assessing the size of responses to nerve stimulation (20 studied, from 13 cells) this activity was first subtracted. Response onset latencies (90 % < 30 ms) and durations showed little or no change. Although most cells were overall more active than during rest both ‘excitatory’ and ‘inhibitory’ responses in both PTNs and non‐PTNs were often markedly reduced in large parts of the step cycle; over some (usually brief) parts responses approached or exceeded their size during rest, i.e. response size was step phase dependent. Such variations occurred without parallel change in the nerve compound action potential, nor were they correlated with the level of background firing at the time that the response was evoked. When responses to both nerves were studied in the same neurone they differed in their patterns of phase dependence. 4 The findings are interpreted as evidence for central mechanisms that, during ‘skilled’, cortically controlled walking, powerfully regulate the excitability of the somatic afferent paths from forelimb mechanoreceptors (including low threshold cutaneous receptors) to motor cortex. Retention (or enhancement) of responsiveness often occurred (especially for ulnar nerve) around footfall, perhaps reflecting a behavioural requirement for sensory input signalling the quality of the contact established with the restricted surface available for support.