Cerebellar cortical activity during antagonist cocontraction and reciprocal inhibition of forearm muscles

1984 ◽  
Vol 51 (1) ◽  
pp. 32-49 ◽  
Author(s):  
R. C. Frysinger ◽  
D. Bourbonnais ◽  
J. F. Kalaska ◽  
A. M. Smith

Monkeys were trained to perform a maintained isometric grip of the thumb and forefinger that elicited a simultaneous cocontraction of the antagonist muscles of the forearm. The same monkeys were also trained to flex and extend the wrist against a stop with the fingers extended and to maintain an isometric wrist position for 1.0-1.5 s. During wrist movement, some of the synergist forearm muscles contracted during both flexion and extension. However, during the maintained isometric wrist position, the prime mover and synergist muscles were reciprocally active or silent. In the culmen-simplex region of the cerebellar cortex bordering on the primary fissure, 62% of the Purkinje cells that were identified by the climbing fiber discharge and that changed firing frequency decreased activity during maintained prehension. Almost all of these same Purkinje cells were reciprocally active during isometric wrist flexion and extension, although three neurons had similar discharge patterns during movements in both directions. In contrast, 79% of the unidentified neurons recorded from the same region of the cerebellar cortex increased discharge frequency during prehension. In general, most of these same neurons had reciprocal patterns of discharge during wrist movement even though a few cells were active during the dynamic phase in both directions. Together, the Purkinje cells and the unidentified neurons with bidirectional response patterns were thought to be related to muscles active during both flexion and extension wrist movements. No cells were found that increased discharge with the static isometric wrist torque exerted in both directions. The discharge frequency of some Purkinje and some unidentified neurons could be shown to be related to prehensile force as well as wrist movement velocity and isometric wrist torque. These data suggest that the discharge of about two-thirds of the Purkinje cells related to forearm muscles located along the borders of the primary fissure may depend on whether antagonist muscles are activated reciprocally or coactively. As a consequence, these cells may play a role in the selection or alternation between either of these two modes of muscular contraction. The increased discharge of the remaining one-third of the Purkinje cells excited during antagonist coactivation may provide inhibition of nuclear cells to stabilize the posture at joints other than the wrist and fingers or, alternatively, they may act to reduce nuclear cell discharge in proportion to the intensity of cutaneous stimulation.

1985 ◽  
Vol 54 (2) ◽  
pp. 231-244 ◽  
Author(s):  
R. Wetts ◽  
J. F. Kalaska ◽  
A. M. Smith

Monkeys were trained to exert a maintained isometric pinch with the thumb and forefinger. This task reliably elicited a simultaneous cocontraction of the forearm muscles. The same monkeys were also taught to insert the open hand into a manipulandum, flex and extend the wrist 35 and 15 degrees, respectively, and maintain an isometric wrist position against a mechanical stop for 1 s. This second task comprised two conditions: a dynamic or movement phase and a static or isometric phase. Movement always involved a wrist displacement of 50 degrees. Although some forearm muscles demonstrated bidirectional activity during the wrist displacement phase, all the wrist and finger muscles were alternatively active in isometric flexion or extension. Of the neurons in the dentate and interposed nuclei that consistently changed discharge during repeated isometric prehension, over 90% (61/67) of the neurons increased activity during this cocontraction of forearm muscles. About 70% (47/67) of these same nuclear cells discharged with a reciprocal pattern of firing during alternating wrist flexion-extension movements. Forty-six neurons had sustained and reciprocal discharge during the maintained isometric wrist postures. No differences were seen between the activity patterns of dentate and interposed cells with respect to either the prehension task or the reciprocal wrist-movement task. The discharge frequency of some dentate and interpositus neurons could be correlated with prehensile force as well as velocity of wrist movement and torque developed by wrist muscles. Correlation coefficients were calculated between nuclear cell discharge and the amplitude of the surface EMGs of the flexors and extensors of the wrist and fingers during the wrist-movement task. Sixteen nuclear cells showed low-order, but reliably positive, correlations with one of the two forearm muscle groups (mean r = 0.33). In contrast, a sample of seven Purkinje cells recorded during the same task demonstrated low-order correlations that were negative in sign (mean r = -0.30) between discharge frequency and one of the two forearm EMGs.


1981 ◽  
Vol 59 (7) ◽  
pp. 733-747 ◽  
Author(s):  
Allan M. Smith

Since Sherrington's convincing demonstration of the reciprocal innervation of opposing muscles, it has generally been thought that antagonist muscles are inactive during most voluntary movements. However, more recent evidence suggests that excitation of Renshaw cells may facilitate antagonist coactivation whereas excitation of Ia inhibitory neurons can induce reciprocal inhibition. A body of evidence has accumulated to indicate some of the circumstances which particularly favour the co-contraction of antagonist muscles. Isometric prehension, either in the precision grip or the power grip, can be shown to be one of the most important examples of antagonist coactivation. Studies of the discharge of single Purkinje cells of the intermediate cerebellar cortex in awake monkeys during performance of a maintained grip revealed that the majority of these neurons are deactivated during antagonist co-contraction. In contrast, other, unidentified neurons of the cerebellar cortex were as a group activated during grasping. It is suggested that the Purkinje cells act to inhibit antagonist muscles during reciprocal inhibition but are themselves inhibited during antagonist coactivation. These results support a suggestion made by Tilney and Pike in 1925 that the cerebellum plays an important role in switching between the coactivation and reciprocal inhibition of antagonist muscles.


2010 ◽  
Vol 103 (4) ◽  
pp. 2039-2049 ◽  
Author(s):  
Brian E. Kalmbach ◽  
Tobin Davis ◽  
Tatsuya Ohyama ◽  
Frank Riusech ◽  
William L. Nores ◽  
...  

We used micro-infusions during eyelid conditioning in rabbits to investigate the relative contributions of cerebellar cortex and the underlying deep nuclei (DCN) to the expression of cerebellar learning. These tests were conducted using two forms of cerebellum-dependent eyelid conditioning for which the relative roles of cerebellar cortex and DCN are controversial: delay conditioning, which is largely unaffected by forebrain lesions, and trace conditioning, which involves interactions between forebrain and cerebellum. For rabbits trained with delay conditioning, silencing cerebellar cortex by micro-infusions of the local anesthetic lidocaine unmasked stereotyped short-latency responses. This was also the case after extinction as observed previously with reversible blockade of cerebellar cortex output. Conversely, increasing cerebellar cortex activity by micro-infusions of the GABAA antagonist picrotoxin reversibly abolished conditioned responses. Effective cannula placements were clustered around the primary fissure and deeper in lobules hemispheric lobule IV (HIV) and hemispheric lobule V (HV) of anterior lobe. In well-trained trace conditioned rabbits, silencing this same area of cerebellar cortex or reversibly blocking cerebellar cortex output also unmasked short-latency responses. Because Purkinje cells are the sole output of cerebellar cortex, these results provide evidence that the expression of well-timed conditioned responses requires a well-timed decrease in the activity of Purkinje cells in anterior lobe. The parallels between results from delay and trace conditioning suggest similar contributions of plasticity in cerebellar cortex and DCN in both instances.


1986 ◽  
Vol 64 (9) ◽  
pp. 1202-1213 ◽  
Author(s):  
Daniel Bourbonnais ◽  
Charles Krieger ◽  
Allan M. Smith

Single unit activity was recorded from the anterior lobe of the cerebellum during ramp and hold stretches of limb muscles in chloralose anesthetized cats. The activity of 95 "phasic" units showed a transient response during dynamic stretch of at least one muscle usually lasting for less than 350 ms following the stimulus onset. The activity of 59 phasic–tonic units was modified not only during dynamic stretch but also during the 1 s of maintained muscle length. All Purkinje cells, identified by their complex spikes, that responded to muscle stretch demonstrated exclusively phasic changes in discharge. Fourteen of 25 Purkinje cells (56%) responded to stretch of both antagonist muscles and these responses were always similar rather than reciprocal. From the 129 units without complex spikes, 70 demonstrated phasic discharge patterns whereas 59 had tonic responses. Seventy-five (59%) of these unidentified units revealed convergent responses to stretch of both antagonists, compared with 54 which responded to stretch of one muscle only. Of the unidentified units receiving convergent afferents from antagonist muscles, 62 (83%) had similar responses and only 13 (17%) had reciprocal reactions. There appeared to be no evidence that muscle afferents alone can induce reciprocal discharge patterns in Purkinje neurons of the cerebellar cortex. The firing frequency of some phasic–tonic units was correlated with both the velocity and amplitude of muscle stretch. No Purkinje cells were found with activity related to either velocity or amplitude of muscle stretch. One phasic and seven phasic–tonic unidentified units were activated at fixed latencies following trains of electrical stimulation applied to the thoracic spinal cord at frequencies exceeding 200 Hz, implying they were terminal portions of mossy fibers originating from direct spinocerebellar tracts. A few recordings of compound potentials were presumed to arise from the cerebellar glomeruli. The changing form of one of these potentials suggested that the glomerulus might be a site at which somatosensory peripheral information is modified by the cerebellar cortex.


2010 ◽  
Vol 103 (1) ◽  
pp. 278-289 ◽  
Author(s):  
W. S. Yu ◽  
H. van Duinen ◽  
S. C. Gandevia

In humans, hand performance has evolved from a crude multidigit grasp to skilled individuated finger movements. However, control of the fingers is not completely independent. Although musculotendinous factors can limit independent movements, constraints in supraspinal control are more important. Most previous studies examined either flexion or extension of the digits. We studied differences in voluntary force production by the five digits, in both flexion and extension tasks. Eleven healthy subjects were instructed either to maximally flex or extend their digits, in all single- and multidigit combinations. They received visual feedback of total force produced by “instructed” digits and had to ignore “noninstructed” digits. Despite attempts to maximally flex or extend instructed digits, subjects rarely generated their “maximal” force, resulting in a “force deficit,” and produced forces with noninstructed digits (“enslavement”). Subjects performed differently in flexion and extension tasks. Enslavement was greater in extension than in flexion tasks ( P = 0.019), whereas the force deficit in multidigit tasks was smaller in extension ( P = 0.035). The difference between flexion and extension in the relationships between the enslavement and force deficit suggests a difference in balance of spillover of neural drive to agonists acting on neighboring digits and focal neural drive to antagonist muscles. An increase in drive to antagonists would lead to more individualized movements. The pattern of force production matches the daily use of the digits. These results reveal a neural control system that preferentially lifts fingers together by extension but allows an individual digit to flex so that the finger pads can explore and grasp.


2021 ◽  
Vol 17 (12) ◽  
pp. e1009609
Author(s):  
Xu Zhang ◽  
Roeland Hancock ◽  
Sabato Santaniello

Transcranial direct current stimulation (tDCS) of the cerebellum has rapidly raised interest but the effects of tDCS on cerebellar neurons remain unclear. Assessing the cellular response to tDCS is challenging because of the uneven, highly stratified cytoarchitecture of the cerebellum, within which cellular morphologies, physiological properties, and function vary largely across several types of neurons. In this study, we combine MRI-based segmentation of the cerebellum and a finite element model of the tDCS-induced electric field (EF) inside the cerebellum to determine the field imposed on the cerebellar neurons throughout the region. We then pair the EF with multicompartment models of the Purkinje cell (PC), deep cerebellar neuron (DCN), and granule cell (GrC) and quantify the acute response of these neurons under various orientations, physiological conditions, and sequences of presynaptic stimuli. We show that cerebellar tDCS significantly modulates the postsynaptic spiking precision of the PC, which is expressed as a change in the spike count and timing in response to presynaptic stimuli. tDCS has modest effects, instead, on the PC tonic firing at rest and on the postsynaptic activity of DCN and GrC. In Purkinje cells, anodal tDCS shortens the repolarization phase following complex spikes (-14.7 ± 6.5% of baseline value, mean ± S.D.; max: -22.7%) and promotes burstiness with longer bursts compared to resting conditions. Cathodal tDCS, instead, promotes irregular spiking by enhancing somatic excitability and significantly prolongs the repolarization after complex spikes compared to baseline (+37.0 ± 28.9%, mean ± S.D.; max: +84.3%). tDCS-induced changes to the repolarization phase and firing pattern exceed 10% of the baseline values in Purkinje cells covering up to 20% of the cerebellar cortex, with the effects being distributed along the EF direction and concentrated in the area under the electrode over the cerebellum. Altogether, the acute effects of tDCS on cerebellum mainly focus on Purkinje cells and modulate the precision of the response to synaptic stimuli, thus having the largest impact when the cerebellar cortex is active. Since the spatiotemporal precision of the PC spiking is critical to learning and coordination, our results suggest cerebellar tDCS as a viable therapeutic option for disorders involving cerebellar hyperactivity such as ataxia.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Andrei Khilkevich ◽  
Juan Zambrano ◽  
Molly-Marie Richards ◽  
Michael Dean Mauk

Most movements are not unitary, but are comprised of sequences. Although patients with cerebellar pathology display severe deficits in the execution and learning of sequences (Doyon et al., 1997; Shin and Ivry, 2003), most of our understanding of cerebellar mechanisms has come from analyses of single component movements. Eyelid conditioning is a cerebellar-mediated behavior that provides the ability to control and restrict inputs to the cerebellum through stimulation of mossy fibers. We utilized this advantage to test directly how the cerebellum can learn a sequence of inter-connected movement components in rabbits. We show that the feedback signals from one component are sufficient to serve as a cue for the next component in the sequence. In vivo recordings from Purkinje cells demonstrated that all components of the sequence were encoded similarly by cerebellar cortex. These results provide a simple yet general framework for how the cerebellum can use simple associate learning processes to chain together a sequence of appropriately timed responses.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Antoine M Valera ◽  
Francesca Binda ◽  
Sophie A Pawlowski ◽  
Jean-Luc Dupont ◽  
Jean-François Casella ◽  
...  

Motor coordination is supported by an array of highly organized heterogeneous modules in the cerebellum. How incoming sensorimotor information is channeled and communicated between these anatomical modules is still poorly understood. In this study, we used transgenic mice expressing GFP in specific subsets of Purkinje cells that allowed us to target a given set of cerebellar modules. Combining in vitro recordings and photostimulation, we identified stereotyped patterns of functional synaptic organization between the granule cell layer and its main targets, the Purkinje cells, Golgi cells and molecular layer interneurons. Each type of connection displayed position-specific patterns of granule cell synaptic inputs that do not strictly match with anatomical boundaries but connect distant cortical modules. Although these patterns can be adjusted by activity-dependent processes, they were found to be consistent and predictable between animals. Our results highlight the operational rules underlying communication between modules in the cerebellar cortex.


2021 ◽  
Author(s):  
Amany Mohamed Shalaby ◽  
Adel Mohamed Aboregela ◽  
Mohamed Ali Alabiad ◽  
Mona Tayssir Sadek

Abstract Diabetes mellitus (DM) represents a widespread metabolic disease with a well-known neurotoxicity in both central and peripheral nervous systems. Oxymatrine is a traditional Chinese herbal medicine that has various pharmacological activities including; anti-oxidant, anti-apoptotic and anti-inflammatory potentials. The present work aimed to study the impact of diabetes mellitus on the cerebellar cortex of adult male albino rat and to evaluate the potential protective role of oxymatrine using different histological methods. Fifty-five adult male rats were randomly divided into three groups: group I served as control, group II was given oxymatrine (80 mg/kg/day) orally for 8 weeks and group III was given a single dose of streptozotocin (50mg/kg) intaperitoneally to induce diabetes. Then diabetic rats were subdivided into two subgroups: subgroup IIIa that received no additional treatment and subgroup IIIb that received oxymatrine similar to group II. The diabetic group revealed numerous changes in the Purkinje cell layer in the form of multilayer arrangement of Purkinje cells, shrunken cells with deeply stained nuclei as well as focal loss of the Purkinje cells. A significant increment in GFAP and synaptophysin expression was reported. Transmission electron microscopy showed irregularity and splitting of myelin sheaths in the molecular layer, dark shrunken Purkinje cells with ill-defined nuclei, dilated Golgi saccules and dense granule cells with irregular nuclear outlines in the granular layer. In contrast, these changes were less evident in diabetic rats that received oxymatrine. In conclusion, Oxymatrine could protect the cerebellar cortex against changes induced by DM.


Neuron ◽  
2016 ◽  
Vol 91 (2) ◽  
pp. 312-319 ◽  
Author(s):  
Laurens Witter ◽  
Stephanie Rudolph ◽  
R. Todd Pressler ◽  
Safiya I. Lahlaf ◽  
Wade G. Regehr

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