Functional Reorganization of the Rat Motor Cortex Following Motor Skill Learning

ArticleinJournal of Neurophysiology 80(6):3321-5 · January 1999with 41 Reads
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Abstract
Functional reorganization of the rat motor cortex following motor skill learning. J. Neurophysiol. 80: 3321-3325, 1998. Adult rats were allocated to either a skilled or unskilled reaching condition (SRC and URC, respectively). SRC animals were trained for 10 days on a skilled reaching task while URC animals were trained on a simple bar pressing task. After training, microelectrode stimulation was used to derive high resolution maps of the forelimb and hindlimb representations within the motor cortex. In comparison with URC animals, SRC animals exhibited a significant increase in mean area of the wrist and digit representations but a decrease in elbow/shoulder representation within the caudal forelimb area. No between-group differences in areal representation were found in either the hindlimb or rostral forelimb areas. These results demonstrate that motor skill learning is associated with a reorganization of movement representations within the rodent motor cortex.
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    Background: Constraint-induced movement therapy (CIMT) promotes upper extremity recovery post stroke, however, it is difficult to implement clinically due to its high resource demand and safety of the restraint. Therefore, we propose that modified CIMT (mCIMT) be used to treat individuals with acute subcortical infarction. Objective: To evaluate the therapeutic effects of mCIMT in patients with acute subcortical infarction, and investigate the possible mechanisms underlying the effect. Methods: The role of mCIMT was investigated in 26 individuals experiencing subcortical infarction in the preceding 14 days. Patients were randomly assigned to either mCIMT or standard therapy. mCIMT group was treated daily for 3 h over 10 consecutive working days, using a mitt on the unaffected arm for up to 30% of waking hours. The control group was treated with an equal dose of occupational therapy and physical therapy. During the 3-month follow-up, the motor functions of the affected limb were assessed by the Wolf Motor Function Test (WMFT) and Motor Activity Log (MAL). Altered cortical excitability was assessed via transcranial magnetic stimulation (TMS). Results: Treatment significantly improved the movement in the mCIMT group compared with the control group. The mean WMF score was significantly higher in the mCIMT group compared with the control group. Further, the appearance of motor-evoked potentials (MEPs) were significantly higher in the mCIMT group compared with the baseline data. A significant change in ipsilesional silent period (SP) occurred in the mCIMT group compared with the control group. However, we found no difference between two groups in motor function or electrophysiological parameters after 3 months of follow-up. Conclusions: mCIMT resulted in significant functional changes in timed movement immediately following treatment in patients with acute subcortical infarction. Further, early mCIMT improved ipsilesional cortical excitability. However, no long-term effects were seen.
  • Article
    Motor cortex is important for motor skill learning, particularly the dexterous skills necessary for our favorite sports and careers. We are especially interested in understanding how plasticity in motor cortex contributes to skill learning. Although human studies have been helpful in understanding the importance of motor cortex in learning skilled tasks, animal models are necessary for achieving a detailed understanding of the circuitry underlying these behaviors and the changes that occur during training. We review data from these models to try to identify sites of plasticity in motor cortex, focusing on rodents as a model system. Rodent neocortex contains well-differentiated motor and sensory regions, as well as neurons expressing similar genetic markers to many of the same circuit components in human cortex. Furthermore, rodents have circuit mapping tools for labeling, targeting, and manipulating these cell types as circuit nodes. Crucially, the projection from rodent primary somatosensory cortex to primary motor cortex is a well-studied corticocortical projection and a model of sensorimotor integration. We first summarize some of the descending pathways involved in making dexterous movements, including reaching. We then describe local and long-range circuitry in mouse motor cortex, summarizing structural and functional changes associated with motor skill acquisition. We then address which specific connections might be responsible for plasticity. For insight into the range of plasticity mechanisms employed by cortex, we review plasticity in sensory systems. The similarities and differences between motor cortex plasticity and critical periods of plasticity in sensory systems are discussed.
  • Article
    Full-text available
    Motor learning is accompanied by widespread changes within the motor cortex, but it is unknown whether these changes are ultimately funneled through a stable corticospinal output channel or whether the corticospinal output itself is plastic. We investigated the consistency of the relationship between corticospinal neuron activity and movement through in vivo two-photon calcium imaging in mice learning a lever-press task. Corticospinal neurons exhibited heterogeneous correlations with movement, with the majority of movement-modulated neurons decreasing activity during movement. Individual cells changed their activity across days, which led to changed associations between corticospinal activity and movement. Unlike previous observations in layer 2/3, activity accompanying learned movements did not become more consistent with learning; instead, the activity of dissimilar movements became more decorrelated. These results indicate that the relationship between corticospinal activity and movement is dynamic and that the types of activity and plasticity are different from and possibly complementary to those in layer 2/3.
  • Article
    Aim of study: To examine the resting motor threshold of the tongue in healthy adults and stroke survivors. Methods: Thirty-five healthy adults were classified into three groups: Group 1 (19–38 years; n = 11), Group 2 (50–64 years; n = 12) and Group 3 (66–78 years; n = 12). Six chronic stroke survivors (mean age =59 years, SD = 9.1 years) were recruited (Group 4). The resting motor thresholds (RMTs) of the tongue were measured and compared (i) among the four groups and (ii) between stroke survivors and age-matched healthy adults. Results: Group 3 showed significantly higher RMTs than Group 1 (p = .001) and 2 (p = 0.007). Group 4 showed significantly higher RMTs than Group 1 (p = .003) and 2 (p = .001). The RMTs of Group 3 and 4 were not significantly different (p = .385). The RMT was positively correlated with age (r = 0.534; p = .001). Group 4 showed significantly higher RMTs than the age-matched controls (U = 2.5, p = .009, r = 0.77). Conclusions: The resting motor threshold of the tongue is significantly increased in adults aged above 65 and in stroke survivors when compared with healthy adults. The findings suggested that the cortical excitability of the tongue deteriorates in the elderly and the stroke population.
  • Article
    Full-text available
    Elaboration of appropriate responses to behavioral situations rests on the ability of selecting appropriate motor outcomes in accordance to specific environmental inputs. To this end, the primary motor cortex (M1) is a key structure for the control of voluntary movements and motor skills learning. Subcortical loops regulate the activity of the motor cortex and thus contribute to the selection of appropriate motor plans. Monoamines are key mediators of arousal, attention and motivation. Their firing pattern enables a direct encoding of different states thus promoting or repressing the selection of actions adapted to the behavioral context. Monoaminergic modulation of motor systems has been extensively studied in subcortical circuits. Despite evidence of converging projections of multiple neurotransmitters systems in the motor cortex pointing to a direct modulation of local circuits, their contribution to the execution and learning of motor skills is still poorly understood. Monoaminergic dysregulation leads to impaired plasticity and motor function in several neurological and psychiatric conditions, thus it is critical to better understand how monoamines modulate neural activity in the motor cortex. This review aims to provide an update of our current understanding on the monoaminergic modulation of the motor cortex with an emphasis on motor skill learning and execution under physiological conditions.
  • Article
    Neural mechanisms that support flexible sensorimotor computations are not well understood. In a dynamical system whose state is determined by interactions among neurons, computations can be rapidly reconfigured by controlling the system's inputs and initial conditions. To investigate whether the brain employs such control mechanisms, we recorded from the dorsomedial frontal cortex of monkeys trained to measure and produce time intervals in two sensorimotor contexts. The geometry of neural trajectories during the production epoch was consistent with a mechanism wherein the measured interval and sensorimotor context exerted control over cortical dynamics by adjusting the system's initial condition and input, respectively. These adjustments, in turn, set the speed at which activity evolved in the production epoch, allowing the animal to flexibly produce different time intervals. These results provide evidence that the language of dynamical systems can be used to parsimoniously link brain activity to sensorimotor computations.
  • Article
    To better understand the neural cortical underpinnings that explain behavioral differences in learning rate, we recorded single unit activity in rat primary motor (M1) and secondary motor (M2) areas while rats learned to perform a directional (left or right) operant visuomotor association task. Analysis of neural activity during the early portion of the cue period showed that neural modulation in the motor cortex was most strongly associated with two task factors: the previous trial outcome (success or error) and the current trial's directional choice (left or right). Furthermore, the fast learners, defined as those who had steeper learning curves and required fewer learning sessions to reach criterion performance, encoded the previous trial outcome factor more strongly than the directional choice factor. Conversely, the slow learners encoded directional choice more strongly than previous trial outcome. These differences in task factor encoding were observed in both the percentage of neurons and the neural modulation depth. These results suggest that fast learning is accompanied by a stronger component of previous trial outcome in the modulation representation present in motor cortex and therefore may be a contributing factor to behavioral differences in learning rate.
  • Article
    At the start of the 21st century, the study of motor behavior is a mature and vibrant scientific field. In this paper, we describe the development of this field by tracing the history of its sub-areas: motor control, motor learning, and motor development. Our understanding of how humans control and coordinate their multi-segmented body in an ever changing environment across the lifespan has grown and matured enormously over the last 100 years. Today, these three sub-areas are converging as our scientific questions build upon the foundations laid by scientists in each of these areas. We end our paper by considering the future in this field and the challenges facing motor behavior scientists in this new century.
  • Article
    Full-text available
    Training and immobilization are powerful drivers of use-dependent plasticity in human primary motor hand area (M1HAND). In young right-handed volunteers, corticomotor representations of the left first dorsal interosseus and abductor digiti minimi muscles were mapped with neuronavigated transcranial magnetic stimulation (TMS) to elucidate how finger-specific training and immobilization interact within M1HAND. A first group of volunteers trained to track a moving target on a smartphone with the left index or little finger for one week. Linear sulcus shape-informed TMS mapping revealed that the tracking skill acquired with the trained finger was transferred to the nontrained finger of the same hand. The cortical representations of the trained and nontrained finger muscle converged in proportion with skill transfer. In a second group, the index or little finger were immobilized for one week. Immobilization alone attenuated the corticomotor representation and pre-existing tracking skill of the immobilized finger. In a third group, the detrimental effects of finger immobilization were blocked by concurrent training of the nonimmobilized finger. Conversely, immobilization of the nontrained fingers accelerated learning in the adjacent trained finger during the first 2 days of training. Together, the results provide novel insight into use-dependent cortical plasticity, revealing synergistic rather than competitive interaction patterns within M1HAND.
  • Article
    Background: Stroke affects widespread brain regions through interhemispheric connections by influencing bilateral motor activity. Several noninvasive brain stimulation techniques have proved their capacity to compensate the functional loss by manipulating the neural activity of alternative pathways. Over the past few decades, brain stimulation therapies have been tailored within the theoretical framework of modulation of cortical excitability to enhance adaptive plasticity after stroke. Objective: However, considering the vast difference between animal and human cerebral cortical structures, it is important to approach specific neuronal target starting from the higher order brain structure for human translation. The present study focuses on stimulating the lateral cerebellar nucleus (LCN), which sends major cerebellar output to extensive cortical regions. Methods: In this study, in vivo stroke mouse LCN was exposed to low-intensity focused ultrasound (LIFU). After the LIFU exposure, animals underwent 4 weeks of rehabilitative training. Results: During the cerebellar LIFU session, motor-evoked potentials (MEPs) were generated in both forelimbs accompanying excitatory sonication parameter. LCN stimulation group on day 1 after stroke significantly enhanced sensorimotor recovery compared with the group without stimulation. The recovery has maintained for a 4-week period in 2 behavior tests. Furthermore, we observed a significantly decreased level of brain edema and tissue swelling in the affected hemisphere 3 days after the stroke. Conclusions: This study provides the first evidence showing that LIFU-induced cerebellar modulation could be an important strategy for poststroke recovery. A longer follow-up study is, however, necessary in order to fully confirm the effects of LIFU on poststroke recovery.
  • Article
    Full-text available
    Procedural motor learning and memory are accompanied by changes in synaptic plasticity, neural dynamics, and synaptogenesis. Missing is information on the spatiotemporal dynamics of the molecular machinery maintaining these changes. Here we examine whether persistent increases in PKMζ, an atypical protein kinase C (PKC) isoform, store long-term memory for a reaching task in rat sensorimotor cortex that could reveal the sites of procedural memory storage. Specifically, perturbing PKMζ synthesis (via antisense oligodeoxynucleotides) and blocking atypical PKC activity (via zeta inhibitory peptide [ZIP]) in S1/M1 disrupts and erases long-term motor memory maintenance, indicating atypical PKCs and specifically PKMζ store consolidated long-term procedural memories. Immunostaining reveals that PKMζ increases in S1/M1 layers II/III and V as performance improved to an asymptote. After storage for 1 month without reinforcement, the increase in M1 layer V persists without decrement. Thus, the persistent increases in PKMζ that store long-term procedural memory are localized to the descending output layer of the primary motor cortex.
  • Article
    Acquisition of new motor skills induces plastic reorganization in the primary motor cortex (M1). Previous studies have demonstrated the increases in the M1 excitability through motor skill learning. However, this M1 reorganization is highly variable between individuals even though they improve their skill performance through the same training protocol. To reveal the source of this inter-individual variability, we examined the relationship between an acquisition of memory-guided feedforward movements and the learning-induced increases in the M1 excitability. Twenty-eight subjects participated in experiment 1. We asked subjects to learn a visuomotor tracking task. The subjects controlled a cursor on a PC monitor to pursue a target line by performing ankle dorsiflexion and plantar flexion. In experiment 1, we removed the online visual feedback provided by the cursor movement once every 6 trials, which enabled us to assess whether the subjects could perform accurate memory-guided movements. Motor evoked potentials (MEP) were elicited in the tibialis anterior muscle by transcranial magnetic stimulation of the relevant M1 before and after the learning of the visuomotor tracking task and after half the trials. We found that the MEP amplitude was increased along with the improvement in memory-guided movements. In experiment 2 (n=10), we confirmed this relationship by examining whether the improvement in memory-guided movements induces increases in MEP amplitude. The results of this study indicate that the plastic reorganization of the M1 induced by the learning of a visuomotor skill is associated with the acquisition of memory-guided movements.
  • Article
    The plasticity of sensorimotor systems in mammals underlies the capacity for motor learning as well as the ability to relearn following injury. Spinal cord injury, which both deprives afferent input and interrupts efferent output, results in a disruption of cortical somatotopy. While changes in corticospinal axons proximal to the lesion are proposed to support the reorganization of cortical motor maps after spinal cord injury, intracortical horizontal connections are also likely to be critical substrates for rehabilitation-mediated recovery. Intrinsic connections have been shown to dictate the reorganization of cortical maps that occurs in response to skilled motor learning as well as after peripheral injury. Cortical networks incorporate changes in motor and sensory circuits at subcortical or spinal levels to induce map remodeling in the neocortex. This review focuses on the reorganization of cortical networks observed after injury and posits a role of intracortical circuits in recovery.
  • Article
    Background: People post-stroke can learn a novel locomotor task but require more practice to do so. Implementing an approach that can enhance locomotor learning may therefore improve post-stroke locomotor recovery. In healthy adults, an acute high-intensity exercise bout before or after a motor task may improve motor learning and has thus been suggested as a method that could be used to improve motor learning in neurorehabilitation. However, it is unclear whether an acute high-intensity exercise bout, which stroke survivors can feasibly complete in neurorehabilitation session, would generate comparable results. Objective: To determine a feasible, high-intensity exercise protocol that could be incorporated into a post-stroke neurorehabilitation session and would result in significant exercise-induced responses. Methods: Thirty-seven chronic stroke survivors participated. We allocated subjects to either a control (CON) or one of the exercise groups: treadmill walking (TMW), and total body exercise (TBE). The main exercise-induced measures were: average intensity (% max intensity) and time spent (absolute: seconds; normalized: % total time) at target exercise intensity, and magnitudes of change in serum lactate (mmol/l) and brain-derived neurotrophic factor (BDNF; ng/ml). Results: Compared to CON, both exercise groups reached and exercised longer at their target intensities and had greater responses in lactate. However, the TBE group exercised longer at target intensity and with greater lactate response than the TMW group. There were no significant BDNF responses among groups. Conclusions: An acute high-intensity exercise bout that could be incorporated into a neurorehabilitation learning-specific session and results in substantial exercise-induced responses is feasible post-stroke.
  • Article
    The corticospinal tract (CST) can become damaged after spinal cord injury or stroke, resulting in weakness or paralysis. Repair of the damaged CST is limited because mature CST axons fail to regenerate, which is partly because the intrinsic axon growth capacity is downregulated in maturity. Whereas CST axons sprout after injury, this is insufficient to recover lost functions. Chronic motor cortex (MCX) electrical stimulation is a neuromodulatory strategy to promote CST axon sprouting, leading to functional recovery after CST lesion. Here we examine the molecular mechanisms of stimulation-dependent CST axonal sprouting and synapse formation. MCX stimulation rapidly upregulates mTOR and Jak/Stat signaling in the corticospinal system. Chronic stimulation, which leads to CST sprouting and increased CST presynaptic sites, further enhances mTOR and Jak/Stat activity. Importantly, chronic stimulation shifts the equilibrium of the mTOR repressor PTEN to the inactive phosphorylated form suggesting a molecular transition to an axon growth state. We blocked each signaling pathway selectively to determine potential differential contributions to axonal outgrowth and synapse formation. mTOR blockade prevented stimulation-dependent axon sprouting. Surprisingly, Jak/Stat blockade did not abrogate sprouting, but instead prevented the increase in CST presynaptic sites produced by chronic MCX stimulation. Chronic stimulation increased the number of spinal neurons expressing the neural activity marker cFos. Jak/Stat blockade prevented the increase in cFos-expressing neurons after chronic stimulation, confirming an important role for Jak/Stat signaling in activity-dependent CST synapse formation. MCX stimulation is a neuromodulatory repair strategy that reactivates distinct developmentally-regulated signaling pathways for axonal outgrowth and synapse formation.
  • Article
    Full-text available
    Background Constraint-induced movement therapy (CIMT) is effective in improving motor outcomes after stroke. However, its existing protocols are resource-intensive and difficult to implement. The aim of this study is to design an easier CIMT protocol using number of repetitions of shaping practice. Method The study design was randomized controlled trial. Participants within 4 weeks after stroke were recruited at Murtala Muhammad Specialist Hospital. They were randomly assigned to groups A, B, C, and D. Group A received 3 hours of traditional therapy. Groups B, C, and D received modified CIMT consisting of 3 hours of shaping practice per session, 300 repetitions of shaping practice in 3 sessions, and 600 repetitions of shaping practice in 3 sessions per day, respectively, and constraint for 90% of the waking hours. All treatment protocols were administered 5 times per week for 4 weeks. The primary outcome was measured using upper limb Fugl-Meyer assessment, while the secondary outcome was measured using motor activity log, Wolf Motor Function Test, and upper limb self-efficacy test at baseline, 2 weeks, and 4 weeks after intervention. Result There were 48 participants 4 weeks after intervention. The result showed that there was no significant difference between groups at baseline (p > 0.05). Within-group improvements attained minimal clinically important difference (MCID) in modified CIMT and 300 repetitions and 600 repetitions groups. Conclusion Number of repetitions of shaping practice significantly improved motor function, real-world arm use, and upper limb self-efficacy after stroke. Therefore, it seems to be a simple alternative for the use of number of hours. Trial Registration This trial is registered with Pan African Clinical Trial Registry (registration number: PACTR201610001828172) (date of registration: 21/10/2016).
  • Article
    Key points: Previous work demonstrated an effect of a single high-intensity exercise bout coupled with motor practice on the retention of a newly acquired skilled arm movement, in both neurologically intact and impaired adults. In the present study, using behavioural and computational analyses we demonstrated that a single exercise bout, regardless of its intensity and timing, did not increase the retention of a novel locomotor task after stroke. Considering both present and previous work, we postulate that the benefits of exercise effect may depend on the type of motor learning (e.g. skill learning, sensorimotor adaptation) and/or task (e.g. arm accuracy-tracking task, walking). Abstract: Acute high-intensity exercise coupled with motor practice improves the retention of motor learning in neurologically intact adults. However, whether exercise could improve the retention of locomotor learning after stroke is still unknown. Here, we investigated the effect of exercise intensity and timing on the retention of a novel locomotor learning task (i.e. split-belt treadmill walking) after stroke. Thirty-seven people post stroke participated in two sessions, 24 h apart, and were allocated to active control (CON), treadmill walking (TMW), or total body exercise on a cycle ergometer (TBE). In session 1, all groups exercised for a short bout (∼5 min) at low (CON) or high (TMW and TBE) intensity and before (CON and TMW) or after (TBE) the locomotor learning task. In both sessions, the locomotor learning task was to walk on a split-belt treadmill in a 2:1 speed ratio (100% and 50% fast-comfortable walking speed) for 15 min. To test the effect of exercise on 24 h retention, we applied behavioural and computational analyses. Behavioural data showed that neither high-intensity group showed greater 24 h retention compared to CON, and computational data showed that 24 h retention was attributable to a slow learning process for sensorimotor adaptation. Our findings demonstrated that acute exercise coupled with a locomotor adaptation task, regardless of its intensity and timing, does not improve retention of the novel locomotor task after stroke. We postulate that exercise effects on motor learning may be context specific (e.g. type of motor learning and/or task) and interact with the presence of genetic variant (BDNF Val66Met).
  • Article
    Full-text available
    Background: Task-oriented therapies have been developed to address significant upper extremity disability that persists after stroke. Yet, the extent of and approach to rehabilitation and recovery remains unsatisfactory to many. Objective: To compare a skill-directed investigational intervention with usual care treatment for body functions and structures, activities, participation, and quality of life outcomes. Methods: On average, 46 days poststroke, 361 patients were randomized to 1 of 3 outpatient therapy groups: a patient-centered Accelerated Skill Acquisition Program (ASAP), dose-equivalent usual occupational therapy (DEUCC), or usual therapy (UCC). Outcomes were taken at baseline, posttreatment, 6 months, and 1 year after randomization. Longitudinal mixed effect models compared group differences in poststroke improvement during treatment and follow-up phases. Results: Across all groups, most improvement occurred during the treatment phase, followed by change more slowly during follow-up. Compared with DEUCC and UCC, ASAP group gains were greater during treatment for Stroke Impact Scale Hand, Strength, Mobility, Physical Function, and Participation scores, self-efficacy, perceived health, reintegration, patient-centeredness, and quality of life outcomes. ASAP participants reported higher Motor Activity Log-28 Quality of Movement than UCC posttreatment and perceived greater study-related improvements in quality of life. By end of study, all groups reached similar levels with only limited group differences. Conclusions: Customized task-oriented training can be implemented to accelerate gains across a full spectrum of patient-reported outcomes. While group differences for most outcomes disappeared at 1 year, ASAP participants achieved these outcomes on average 8 months earlier (ClinicalTrials.gov: Interdisciplinary Comprehensive Arm Rehabilitation Evaluation [ICARE] Stroke Initiative, at www.ClinicalTrials.gov/ClinicalTrials.gov . Identifier: NCT00871715).
  • Article
    This study aimed to identify the ipsilateral corticospinal responses of the contralateral limb following different types of unilateral motor-training. Three groups performing unilateral slow-paced strength training (SPST), non-paced strength training (NPST) or visuomotor skill training (VT) were compared to a control group. It was hypothesised that 4 weeks of unilateral SPST and VT, but not NPST, would increase ipsilateral corticospinal excitability (CSE) and reduce short-interval cortical inhibition (SICI), resulting in greater performance gains of the untrained limb. Tracking error of the untrained limb reduced by 29 and 41% following 2 and 4 weeks of VT. Strength of the untrained limb increased by 8 and 16% following 2 and 4 weeks of SPST and by 6 and 13% following NPST. There was no difference in cross-education of strength or tracking error. For the trained limb, SPST and NPST increased strength (28 and 26%), and VT improved by 47 and 58%. SPST and VT increased ipsilateral CSE by 89 and 71% at 2 weeks. Ipsilateral CSE increased 105 and 81% at 4 weeks following SPST and VT. The NPST group and control group showed no changes at 2 and 4 weeks. SPST and VT reduced ipsilateral SICI by 45 and 47% at 2 weeks; at 4 weeks, SPST and VT reduced SICI by 48 and 38%. The ipsilateral corticospinal responses are determined by the type of motor-training. There were no differences in motor performance between SPST, NPST and VT. The data suggests that the corticospinal responses to cross-education are different and determined by the type of motor-training.
  • Article
    Introduction: Studies on upper limb constraint-induced movement therapy (CIMT) showed that using number of repetitions of task practice is effective. The aim of this study is to translate this to the lower limb. Method: The study is a randomised controlled trial (RCT) comparing a protocol using number of repetitions with a protocol using hours of task practice. Stroke patients with asymmetrical stance, ability to stand and walk with minimal assistance, and with no significant cognitive impairment will be randomised into two groups, A and B. Group A will perform 600 repetitions of tasks per day, 5 days a week for four weeks. Group B will perform task practice for three hours a day for the same period. In both groups, participants will be asked to restrict the use of the unaffected limb during the training session (behavioural constraint). Outcomes of the study will be assessed using lower limb Fugl Meyer, lower extremity motor activity log (LE-MAL), Rivermead mobility index (RMI), Berg balance scale (BBS), modified Ashworth scale (MAS), 6-minute walk test (6MWT) and 10-metre walk test (10MWT). Demographic characteristics of the participants will be analysed using descriptive statistics; while the data on the outcomes of interest will be analysed using t-test and repeated measures ANOVA or the non-parametric equivalent.
  • Article
    Full-text available
    Mammalian motor cortex consists of several interconnected subregions thought to play distinct roles in voluntary movements, yet their specific role in decision making and execution is not completely elucidated. Here we used transient optogenetic inactivation of the caudal forelimb area (CFA) and rostral forelimb area (RFA) in mice as they performed a directional joystick task. Based on a vibrotactile cue applied to their forepaw, mice were trained to push or pull a joystick after a delay period. We found that choice and execution are temporally segregated processes. CFA and RFA were both essential during the stimulus delivery for correct choice and during the answer period for motor execution. Fine, distal motor deficits were restricted to CFA inactivation. Surprisingly, during the delay period neither area alone, but only combined inactivation was able to affect choice. Our findings suggest transient and partially distributed neural processing of choice and execution across different subregions of the motor cortex.
  • Chapter
    Advances in the fields of medicine, biology, physiology, and electronics have ushered in the development of a wide variety of devices to interface with the nervous system in order to restore sensory or motor function after an injury or disease. This field of neural prosthetic devices has now made an important advancement from using the activity of peripheral nerves or muscles to acquire a control signal to implanting devices directly into the brain or central nervous system (CNS) to extract command signals from populations of single neurons regarding the intention to move and to stimulate into the CNS to restore some kind of sensory information. This technological achievement to open novel lines of communication between the populations of single neurons and external devices is often referred to as Brain–Machine Interfaces (BMI) or neurorobotics. This chapter will focus on this fast growing field of neurorobotics in which CNS neuroprosthetic devices that use recording microelectrodes in the brain to capture information from populations of single neurons to create a command signal for a device or machine that can then restore some function to the patient.
  • Article
    The behavioural impairments and subsequent recovery were studied in rats with circumscribed unilateral lesions in the somatic sensorimotor cortex (SMC). Lesions were made in the caudal forelimb region (CFL), the rostral forelimb region (RFL), the anteromedial cortex (AMC) or the hindlimb area. Rats with damage in the CFL produced a deficit in placing the forelimb contralateral to the lesion during exploratory locomotion on a grid surface. Rats with AMC damage circled in the direction ipsilateral to the lesion. Lesions in the CFL or AMC produced an ipsilateral somatosensorimotor asymmetry on the bilateral-stimulation test (responding to adhesive patches placed on the contralateral forelimb was slower) that recovered in 7 days following AMC lesions or 28 days following CFL lesions. Finally, RFL lesions produced an ipsilateral asymmetry on the bilateral-stimulation task that was more severe and enduring (recovery in 60 days). After behavioral recovery, the effects of an additional lesion placed in the homotopic contralateral cortex were examined (two-stage bilateral lesion). Rats receiving two-stage bilateral lesions in the RFL or CFL responded slower to tactile stimulation of the forelimb contralateral to the second lesion. In the case of CFL-damaged rats, placing deficits also appeared contralateral to the most recent injury. In contrast, rats receiving two-stage bilateral AMC lesions did not exhibit behavioral asymmetries following the second lesion. These results provide evidence to suggest that subdivisions of the rat SMC can be distinguished with lesion/behavioral experiments. Moreover, a comparison of the effects of unilateral and two-stage bilateral lesions may help in the parcellation of the rat SMC into functionally distinct subareas and provide a basis for studying the processes of recovery and maintenance of function following brain damage.
  • Integrative and Molecular Approaches to Brain Function, edited by Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys
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  • AND support for the presence of a premotor or supplementary motor cortical area
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  • Synaptogenesis and fos expression in the motor cortex of the adult rat after complex motor skill acquisition A chronic unit study of the sensory properties of neurons in the forelimb areas of rat sensorimotor cortex
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    • C F And Neafsey
    GREENOUGH, W. T. Synaptogenesis and fos expression in the motor cortex of the adult rat after complex motor skill acquisition. J. Neurosci. SIEVERT, C. F. AND NEAFSEY, E. J. A chronic unit study of the sensory properties of neurons in the forelimb areas of rat sensorimotor cortex. 16: 4529-4535, 1996.
  • Repetitive microstimulation alters the cortical representation of movements in adult rats Changes in membrane currents during Pavlovian conditioning of single cortical neurons
    • R J Jenkins
    • W M And Merzenich
    • M M Soma-Woody
    • C D Gruen
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    NUDO, R. J., JENKINS, W. M., AND MERZENICH, M. M. Repetitive microstimulation alters the cortical representation of movements in adult rats. Soma-WOODY, C. D., GRUEN, E., AND BIRT, D. Changes in membrane currents during Pavlovian conditioning of single cortical neurons. Brain Res. 539: tosens. Mot. Res. 7: 463-483, 1990.
  • Article
    It is now clear that the motor cortex of adult mammals is capable of widespread functional reorganization. After specific types of motor skill training, the cortical representations of the movements used to perform the task expand, invading adjacent motor representations. After peripheral nerve injury, representations of unaffected muscles expand, invading those of the denervated muscles. After focal cortical injury, representations in the uninjured, adjacent cortical tissue undergo widespread alterations. Specific changes are dependent upon the use of the affected limb during the postinjury period. It now appears likely that motor map alterability results from changes in synaptic efficacy of intrinsic horizontal connections within motor cortex. Taken together, these studies suggest that the neurophysiological circuitry underlying muscle and movement maps within primary motor cortex is continually remodeled throughout an individual's life. The functional organization of motor cortex is constantly reshaped by behavioral demands for the learning of new motor skills.
  • Article
    Evidence supports the view that 'memory traces' are formed in the hippocampus and in the cerebellum in classical conditioning of discrete behavioural responses. In the hippocampus learning results in long-lasting increases in excitability of pyramidal neurons that resemble the phenomenon of long-term potentiation. Although it plays a role in certain aspects of conditioning, the hippocampus is not necessary for learning and memory of the basic conditioned responses. The cerebellum and its associated brain-stem circuitry, on the other hand, does appear to be essential (necessary and sufficient) for learning and memory of the conditioned response. Evidence to date supports the view that mossy fibre convey conditioned stimulus information and that climbing fibres conveys the critical 'reinforcement' information to the cerebellum and that 'memory traces' appear to be formed in cerebellar cortex and interpositus nucleus.
  • Article
    The primary motor cortex (MI) contains a map organized so that contralateral limb or facial movements are elicited by electrical stimulation within separate medial to lateral MI regions. Within hours of a peripheral nerve transection in adult rats, movements represented in neighboring MI areas are evoked from the cortical territory of the affected body part. One potential mechanism for reorganization is that adjacent cortical regions expand when preexisting lateral excitatory connections are unmasked by decreased intracortical inhibition. During pharmacological blockade of cortical inhibition in one part of the MI representation, movements of neighboring representations were evoked by stimulation in adjacent MI areas. These results suggest that intracortical connections form a substrate for reorganization of cortical maps and that inhibitory circuits are critically placed to maintain or readjust the form of cortical motor representations.
  • Article
    Single electrode voltage clamp recordings were made during Pavlovian conditioning of single units of the motor cortex of cats. Units that developed a conditioned spike discharge in response to a click conditioned stimulus (CS) after pairing the click with glabella tap and local ionophoretic application of glutamate showed increases in input resistance and reductions of an early outward current induced by depolarizing commands and by return to holding potentials after hyperpolarizing commands. Changes in later currents were also found in some cells. Units that failed to develop a conditioned response did not show these changes. The decreases in membrane currents could contribute to an increased spike discharge in response to the CS as could the increased input resistance observed after conditioning. Conductance changes of this type may serve as engrams by which some forms of memory and learning are expressed across both vertebrate and invertebrate species.
  • Article
    The movements of rats trained to reach through an aperture for food pellets, located on a shelf, were videorecorded and filmed from lateral and ventral perspectives for analysis using Eshkol-Wachman Movement Notation (EWMN). Reaching was subdivided into phases of locating the food and advancing the limb to grasp the food, bringing the food to the mouth, and returning to the starting position. Further analysis of the movements comprising these acts revealed a number of novel findings. (1) Most of the first phase of the movement is produced proximally, with the limb lifted, aimed, and advanced from the shoulder. (2) After the limb is lifted from the substrate to initiate reaching, it is carried to a parasagittal position so that the long axis of the forearm is aligned along the midline of the body. This aspect of the movement 'aims' the limb toward the target. (3) The digits are opened as the limb is advanced from the aiming position toward the food. As the paw approaches the food, pronation of the palm is accomplished by abduction of the upper arm. (4) As the limb is retracted, the digits are closed to grasp the food. As retraction ends, the paw is supinated by a rotatory movement at the wrist. This is the only distal rotatory movement. (5) The position taken by the second forelimb, as it is adducted to aid in holding the food pellet for eating, resembles the 'aiming' posture. The results are discussed in reference to the kinematics, neural control, and the evolutionary origins of reaching in the rat and other animals. Additionally, the results provide a framework for analysis of changes in movements produced by physiological manipulations.
  • Article
    In order to examine the effects of repetitive stimulation on functional cortical organization, standard intracortical microstimulation (ICMS) techniques were used to generate maps of movement representations in motor cortex of rat. After identification of caudal and rostral forelimb fields and adjacent vibrissae and neck fields, one or more representational borders were defined in greater detail. Then a microelectrode was introduced into one of these representational fields, and ICMS current pulses were delivered at a rate of 1/sec for 1 to 3 hr. Following repetitive ICMS, significant changes in movement representations were observed using current levels that were either suprathreshold or subthreshold for evoking the site-specific movement. Electromyographic activity could be evoked at suprathreshold and near-threshold current levels, but not at the subthreshold current levels used here. Significant border shifts ranged from 210 to 670 microns. In each case in which shifts occurred, there appeared to be expansion of the movement represented at the repetitively stimulated site. The effects were progressive and reversible. These results suggest that at least under these unusual experimental circumstances, large representational changes can be generated very rapidly within motor cortex in the absence of any evident peripheral feedback.
  • Article
    In the accompanying paper (Sanes et al. 1989), we demonstrated that the map of motor cortex (MI) output was reorganized when examined 1 week to 4 months after a motor nerve lesion in adult rats. The present experiments measured the extent of functional reorganization that occurs within the first hours after this lesion. Shifts in MI output were examined by testing the effect of stimulation at a site in MI vibrissa area before and up to 10 h after nerve section of the branches of the facial nerve that innervate the vibrissa. Immediately following nerve transection, no movement or forelimb EMG activity was evoked by intracortical electrical stimulation within the vibrissa area. Within hours of the nerve transection, however, stimulation elicited forelimb EMG responses that were comparable to those obtained by stimulating within the pre-transection forelimb area. Remapping of MI after nerve transection indicated that the forelimb boundary had shifted about 1 mm medially from its original location into the former vibrissa territory. Forelimb EMG could be evoked for up to 10 h within this reorganized cortex. These results indicated that the output circuits of MI can be quickly reorganized by nerve lesions in adult mammals.
  • Reshaping the cortical motor map by unmasking latent intracortical connections forepaw motor control following unilateral motor cortical ablations
    • A W Fowler
    • S C Deficits
    • K M And
    • J P Donoghue
    PRICE, A. W. AND FOWLER, S. C. Deficits in contralateral and ipsilateral JACOBS, K. M. AND DONOGHUE, J. P. Reshaping the cortical motor map by unmasking latent intracortical connections. Science 251: 944-945, 1991. forepaw motor control following unilateral motor cortical ablations. Brain Res. 205: 81-90, 1981.
  • Article
    Effects of motor training on a neocortical nerve cell population involved in performance of the motor task were assessed by measuring Layer V pyramidal neuron apical dendritic branching in motor-sensory forelimb cortex of rats trained to reach into a tube for food. Rats were trained to reach with the forepaw they preferred to use (group PRAC), the nonpreferred forepaw (REV), both forepaws (ALT), or neither forepaw (CONT). Across groups, hemispheres opposite trained forepaws had larger apical dendritic fields, in terms of total dendritic length, number of oblique branches from the apical shaft, and length of terminal branches. Similar, although somewhat less consistent, effects were seen when results were analyzed for between- (CONT vs ALT) and within-subject comparisons (trained vs nontrained hemispheres of REV and PRAC). This finding is compatible with the hypothesis that altered dendritic patterns, with associated synapses, are involved in storage of information from the training experience. The within-subject effects mitigate suggestions that these differences arise from generally acting hormonal or metabolic consequences of the training experience, although the possibility that these effects result from neural activity per se and are unrelated to information storage cannot be excluded.
  • Article
    We have previously reported that training rats to reach for bits of cookies resulted in an increase in dendritic length and branching complexity in the apical branches of layer V pyramidal cells within the motor-sensory forelimb cortex. In this paper, we describe the effects of reach training upon the basilar branches of two subpopulations of pyramidal cells in layers II and III. The two subpopulations of pyramids are distinguishable by morphological characteristics and location within layers II and III. The basilar dendrites of one subtype, the forked apical pyramid, are selectively altered in size and complexity during reach training; whereas the other subtype, the single shaft apical cells, do not measurably change during training. Based upon these findings, we postulate that these cells may have different roles in governing the reaching behavior.
  • Article
    The vestibulo-ocular reflex (VOR) stabilizes retinal images by generating smooth eye movements that are equal in amplitude and opposite in direction to head turns. Whenever image motion occurs persistently during head turns, the VOR undergoes motor learning; as a result image stability is gradually restored. A group of brain stem neurons that are in the modified pathways has now been described. The neurons express changes in firing in association with motor learning in the VOR and receive monosynaptic inhibition from the flocculus of the cerebellum. The changes in firing have an appropriate magnitude and are expressed at the correct latency to account for the altered VOR. The response properties of the neurons point to their brain stem vestibular inputs for further investigation of the site of motor learning.
  • Article
    The sensory properties of neurons in the several forelimb areas of rat sensorimotor cortex were examined using the technique of extracellular single-unit recording in the awake, head-restrained rat. Cells with peripheral receptive fields were tested for the amount and modality of sensory input during joint manipulation and brushing and tapping of limbs, face and trunk. Input-output correlations were made on the basis of the results of receptive field mapping and intracortical microstimulation in the same electrode penetration. It was found that neurons (n = 117) in the rostral forelimb area receive virtually no sensory input while 30% of neurons (n = 114) in the caudal forelimb primary motor area do receive such input. The inputs to caudal forelimb motor area neurons were primarily (83%) from single joints; along perpendicular electrode penetrations the same joint that activated a cortical cell also moved when microstimulation was delivered along the same electrode penetration. In the granular and dysgranular zones of somatic sensory forelimb cortex, 70% of neurons (n = 82) were responsive to peripheral sensory inputs, with most of the cells in the granular cortex responsive to cutaneous inputs while cells in the dysgranular cortex were more responsive to deep inputs. The lack of sensory inputs to the rostral forelimb motor area is consistent with the proposal that this region may be a part of the supplementary motor area of the rat.
  • Article
    In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rat's supplementary motor area. Both of these motor representations give rise to direct corticospinal projections, some of which may make monosynaptic connections with cervical enlargement motoneurons. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rat's frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.
  • Article
    Features of neuronal activity in two subdivisions of primary motor cortex (MI) were recorded in awake rats. Neurons in the caudal part of MI, which overlaps part of the somatic sensory cortex, discharge with brief bursts in conjunction with isometric bar pressing with the forelimb. Cells in this caudal region are activated by cutaneous stimuli. In the rostral part of MI, neurons discharge prior to and during forelimb force changes, begin to discharge earlier than in the caudal zone, and have non-cutaneous or unidentifiable receptive fields. These results suggest separate motor control functions for rostral and caudal parts of rat MI.
  • Article
    The ability of rats to perform a discrete digital task after cortical lesions was studied. Six out of 8 rats with bilateral, frontal cortex ablation demonstrated a large drop in performance levels which persisted througout the 3 month testing period. Animals with occipital cortex lesions showed no postoperative drop in performance.
  • Article
    Intracortical microstimulation of 40--50 points in the frontal cortex of ketamine-anesthetized rats using perpendicular penetrations has demonstrated a second forelimb area located rostrally near the frontal pole as well as confirming the existence of a more caudally located forelimb area just anterior to bregma. Cortex where neck and/or vibrissae movements were evoked separated the two forelimb areas. The rostral and caudal forelimb areas defined by microstimulation correspond with patches of corticospinal neurons labeled with HRP following injections of this tracer into the cervical enlargement. Digit movements were commonly evoked from the rostral forelimb area but were rarely elicited from the caudal forelimb area. The question of whether the rostral forelimb region is part of primary or supplementary motor cortex is not yet able to be answered.
  • Article
    Two force transducers which were interfaced with a minicomputer were used as operant manipulanda to assess changes in peak force and rate of response produced by unilateral motor cortical lesions in rats. Spatial arrangement of the manipulanda permitted a subject to respond on Transducer I exclusively with his left forepaw and on Transducer II exclusively with his right. Permanent deficits as measured by both force and rate of response were observed for the limb contralateral to the lesion. In the forelimb ipsilateral to the lesion rate of response was severely depressed immediately following the lesion and, although there was marked recovery during the 10-12 days following surgery, post-lesion rates never attained pre-lesion levels.
  • Article
    Although it was once thought that the corticospinal (pyramidal) tract was the main substrate of voluntary movement, the extent to which it is involved in the control of proximal vs. distal musculature, independent finger movements, and movements characteristic of different species of animals now is unclear. The objective of this study was to examine the effects of pyramidal tract lesions on skilled forelimb use in rats. In addition, cell morphology in motor cortex following lesions was examined. Naive and trained rats received unilateral pyramidal sections just rostral to the pyramidal decussation. Performance was assessed and filmed on two reaching tasks. Measures of reaching consisted of success in obtaining food, kinematic analysis of limb trajectory and velocity, and qualitative evaluation of 10 movement components comprising a reach. Pyramidal tract lesions only impaired reaching for single food pellets. Almost all movements comprising a reach, except digit opening, were impaired, including lifting, aiming, pronating and supinating the limb, and releasing food. Although success in limb use was unchanged over the 180 day observation period, there were significant improvements in the qualitative features of limb use. Histologically, the morphology of pyramidal cells in the forelimb area ipsilateral to the lesion seemed normal. Rats with additional damage to adjacent structures, such as the medial lemniscus and olivary complex, were much more severely impaired on the reaching tasks, and displayed similar impairments as judged by qualitative and kinematic measures. The results demonstrate that a number of movements involved in independent limb use are chronically impaired by pyramidal tract lesions in the rat. Nevertheless, significant use of the limb is possible, due perhaps to both the contribution of extrapyramidal motor systems and the influence of the remaining pyramidal system through its extrapyramidal connections. The results not only show that the rat pyramidal tract supports functions very similar to those of primates and thus might provide a good model for some aspects of pyramidal tract dysfunctions, but also they argue that the pyramidal tract is involved in both proximal and distal limb movements.
  • Article
    The existence of multiple motor cortical areas that differ in some of their properties is well known in primates, but is less clear in the rat. The present study addressed this question from the point of view of connectional properties by comparing the afferent and efferent projections of the caudal forelimb area (CFA), considered to be the equivalent of the forelimb area of the primary motor cortex (MI), and a second forelimb motor representation, the rostral forelimb area (RFA). As a result of various tracing experiments (including double labeling), it was observed that CFA and RFA had reciprocal corticocortical connections characterized by preferential, asymmetrical, laminar distribution, indicating that RFA may occupy a different hierarchical level than CFA, according to criteria previously discussed in the visual cortex of primates. Furthermore, it was found that RFA, but not CFA, exhibited dense reciprocal connections with the insular cortex. With respect to their efferent projection to the basal ganglia, it was observed that CFA projected very densely to the lateral portion of the ipsilateral caudate putamen, whereas the contralateral projection was sparse and more restricted. The ipsilateral projection originating from RFA was slightly less dense than that from CFA, but it covered a larger portion of the caudate putamen (in the medial direction); the contralateral projection from RFA to the caudate putamen was of the same density and extent as the ipsilateral projection. The reciprocal thalamocortical and corticothalamic connections of RFA and CFA differed from each other in the sense that CFA was mainly interconnected with the ventrolateral thalamic nucleus, while RFA was mainly connected with the ventromedial thalamic nucleus. Altogether, these connectional differences, compared with the pattern of organization of the motor cortical areas in primates, suggest that RFA in the rat may well be an equivalent of the premotor or supplementary motor area. In contrast to the corticocortical, corticostriatal, and thalamocortical connections, RFA and CFA showed similar efferent projections to the subthalamic nucleus, substantia nigra, red nucleus, tectum, pontine nuclei, inferior olive, and spinal cord.
  • Article
    We mapped movement representations in motor cortex of rats that had their mystacial vibrissae (whiskers) clipped continually for various periods during their development. In animals clipped since birth, and in adult animals clipped for 5 days, there was a significant reduction in the ratio of whisker to forelimb representation areas. Allowing the whiskers to regrow for at least 72 h resulted in normal-appearing representation patterns. The plasticity of motor representations induced by whisker clipping, and that following whisker regrowth, were not age dependent. These findings indicate that a relatively innocuous procedure that restricts sensory and motor functions results in pronounced, and reversible, changes in the functional organization of the motor cortex.
  • Article
    This study investigates the influence of early somatosensory experience on shaping movement representation patterns in motor cortex. Electrical microstimulation was used to map bilaterally the motor cortices of adult rats subjected to altered tactile experience by unilateral vibrissa trimming from birth (birth-trimmed group) or for comparable periods that began in adulthood (adult-trimmed group). Findings demonstrated that (1) vibrissa trimming from birth, but not when initiated in adulthood, led to a significantly smaller-sized primary motor cortex (M1) vibrissa representation in the hemisphere contralateral to the trimmed vibrissae, with no evidence for concomitant changes in size of the adjacent forelimb representation or the representation of the intact vibrissae in the opposite (ipsilateral) hemisphere; (2) in the contralateral hemispheres of the birth-trimmed group, an abnormal pattern of evoked vibrissa movement was evident in which bilateral or ipsilateral (intact) vibrissa movement predominated; (3) in both hemispheres of the birth-trimmed group, current thresholds for eliciting movement of the trimmed vibrissa were significantly lower than normal; and (4) in the adult-trimmed group, but not in the birth-trimmed group, there was a decrease bilaterally in the relative frequency of dual forelimb-vibrissa sites that form the common border between these representations. These results show that sensory experience early in life exerts a significant influence in sculpting motor representation patterns in M1. The mature motor cortex is more resistant to the type and magnitude of influence that tactile experience has on developing M1, which may indicate that such an influence is constrained by a developmentally regulated critical period.
  • Article
    Full-text available
    Complex motor skill learning, but not mere motor activity, leads to an increase in synapse number within the cerebellar cortex. The present experiment used quantitative electron microscopy to determine which synapse types were altered in number. Adult female rats were allocated to either an acrobatic condition (AC), a voluntary exercise condition (VX), or an inactive condition (IC). AC animals were trained to traverse an elevated obstacle course requiring substantial motor coordination to complete. VX animals were housed with unlimited access to running wheels and IC animals received no motor training but were handled briefly each day. Results showed the AC animals to have significantly more parallel fiber to Purkinje cell synapses than both the VX and IC animals. No other synapse type was significantly altered. Thus, the learning-dependent increase in synapse number observed within the cerebellar cortex is accomplished primarily through the addition of parallel fiber synapses.