The cerebellum in maintenance of a motor skill: A hierarchy of brain and spinal cord plasticity underlies H-reflex conditioning

Wolpaw, Jonathan R.; Chen, Xiang Yang

doi:10.1101/lm.92706

Cited by 58 publications

(58 citation statements)

References 78 publications

(64 reference statements)

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“…As noted in the introduction, the changes in GABAergic function associated with operant conditioning of the H-reflex are part of a complex pattern of plasticity at spinal and supraspinal sites (see Wang et al 2006aWang et al , 2009Wolpaw and Chen 2006;Wolpaw 2010 for review). The effects of SMC stimulation may be similarly complex.…”

Section: Discussionmentioning

confidence: 99%

Cortical stimulation causes long-term changes in H-reflexes and spinal motoneuron GABA receptors

Wang

Chen

et al. 2012

Journal of Neurophysiology

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The cortex gradually modifies the spinal cord during development, throughout later life, and in response to trauma or disease. The mechanisms of this essential function are not well understood. In this study, weak electrical stimulation of rat sensorimotor cortex increased the soleus H-reflex, increased the numbers and sizes of GABAergic spinal interneurons and GABAergic terminals on soleus motoneurons, and decreased GABA A and GABA B receptor labeling in these motoneurons. Several months after the stimulation ended the interneuron and terminal increases had disappeared, but the H-reflex increase and the receptor decreases remained. The changes in GABAergic terminals and GABA B receptors accurately predicted the changes in H-reflex size. The results reveal a new long-term dimension to corticalspinal interactions and raise new therapeutic possibilities. brain stimulation; spinal cord plasticity; GABAergic terminal, interneuron, and receptor; learning and memory THE IMMEDIATE EFFECTS of cortical neuronal activity on the spinal cord are widely studied (e.g., Alstermark and Isa 2012), but its long-term effects have received much less attention. Nevertheless, during development and throughout life the cortex gradually changes spinal pathways to support the acquisition and maintenance of skills such as locomotion, and impairments in this regulation contribute to the disabilities produced by strokes, spinal cord injuries, and other disorders (Knikou 2010;Wolpaw 2010). The mechanisms of this long-term regulation are poorly understood. We are using long-term cortical regulation of the H-reflex, the electrical analog of the spinal stretch reflex (SSR), as a model for studying this important cortical function. The H-reflex, the simplest behavior of the vertebrate CNS, is produced by a wholly spinal and largely monosynaptic pathway consisting of the primary afferent neuron, the motoneuron, and the synapse between them.In primates and rodents, an operant conditioning protocol can change sensorimotor cortex (SMC) activity and thereby gradually increase or decrease H-reflex size (Wolpaw 2010; Wolpaw and Chen 2009). These larger or smaller reflexes, which persist after conditioning ends, are simple motor skills (i.e., adaptive behaviors acquired through practice; Compact Oxford English Dictionary 1993). The reflex changes are produced and maintained by a complex hierarchy of plasticity at both spinal and supraspinal sites Wolpaw 2010 for review). While much remains to be learned about this hierarchy and the sites and mechanisms of plasticity, it is clear that SMC activity modifies the H-reflex by producing changes in the motoneuron (e.g., in firing threshold), as well as elsewhere in the spinal cord. Recent studies showing that operantly conditioned H-reflex decreases are accompanied by marked changes in GABAergic interneurons in the ventral horn and in GABAergic terminals on spinal motoneurons suggest that changes in GABAergic function may play a key role in producing the motoneuron plasticity directly underlying H-reflex ...

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Section: Discussionmentioning

confidence: 99%

Cortical stimulation causes long-term changes in H-reflexes and spinal motoneuron GABA receptors

Wang

Chen

et al. 2012

Journal of Neurophysiology

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“…In the first 24 h after the injections, exploratory behavior was attenuated. In subsequent days, they displayed postural and locomotor signs similar to those seen after cerebellar nuclear ablation in our previous studies Wolpaw and Chen 2006) (e.g., splaying of the back limbs, holding the trunk close to the ground, limb rigidity, intermittent hopping locomotion, occasional oscillatory head movements). These signs disappeared within 14 days.…”

Section: Methodsmentioning

confidence: 76%

“…All procedures were in accordance with the Guide for the Care and Use of Laboratory Animals (National Academy Press, 2011) and had been approved by the Institutional Animal Care and Use Committee of the Wadsworth Center. The protocols for implantation of the nervestimulating cuff and EMG recording electrodes, M-response and H-reflex elicitation, H-reflex conditioning, and data collection and analysis in freely moving rats have been fully described previously (Chen and Wolpaw 1995Wolpaw and Chen 2006;Wolpaw and Herchenroder 1990) and are reviewed here. The procedures for IO ablation and histological evaluation are described in detail below.…”

Section: Methodsmentioning

confidence: 99%

Ablation of the inferior olive prevents H-reflex down-conditioning in rats

Chen

Wang

Chen

et al. 2016

Journal of Neurophysiology

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We evaluated the role of the inferior olive (IO) in acquisition of the spinal cord plasticity that underlies H-reflex down-conditioning, a simple motor skill. The IO was chemically ablated before a 50-day exposure to an operant conditioning protocol that rewarded a smaller soleus H-reflex. In normal rats, down-conditioning succeeds (i.e., H-reflex size decreases at least 20%) in 80% of animals. Down-conditioning failed in every IO-ablated rat (P Ͻ 0.001 vs. normal rats). IO ablation itself had no long-term effect on H-reflex size. These results indicate that the IO is essential for acquisition of a down-conditioned H-reflex. With previous data, they support the hypothesis that IO and cortical inputs to cerebellum enable the cerebellum to guide sensorimotor cortex plasticity that produces and maintains the spinal cord plasticity that underlies the down-conditioned H-reflex. They help to further define H-reflex conditioning as a model for understanding motor learning and as a new approach to enhancing functional recovery after trauma or disease. operant conditioning; spinal cord; plasticity; cerebellum; learning EVEN THE SIMPLEST LEARNING produces plasticity at multiple places in the CNS (e.g., Carrier et al. 1997;Lieb and Frost 1997;Longley and Yeo 2014;Wolpaw and Lee 1989). Thus a central challenge in understanding learning is to explain how changes at many sites combine to account for the acquisition and maintenance of a newly learned behavior, and also for the preservation of previously learned behaviors that use some of the same neurons and synapses. Operant conditioning of the H-reflex, an electrical analog of the spinal stretch reflex (e.g., the knee-jerk reflex), provides a unique opportunity to address the challenge. By a standard definition of motor skill as an adaptive behavior acquired through practice (e.g., Shmuelof and Krakauer 2011), operantly conditioned change in the H-reflex is a simple motor skill. This learning changes both the brain and the spinal cord (Wolpaw and Chen 2006; see Thompson and Wolpaw 2014 and Wolpaw 2010 for review). The anatomical separation of the spinal cord from the brain and the direct connection of the spinal cord to behavior (i.e., to muscle activity) facilitate study of the manner in which the spinal and supraspinal plasticity produced by H-reflex conditioning combine to acquire and maintain a smaller (i.e., down-conditioned) or larger (i.e., up-conditioned) H-reflex, while at the same time maintaining other behaviors that use the same spinal circuitry.The studies to date indicate that the corticospinal tract (CST) and cerebellar output to cortex are essential for acquisition of the spinal cord plasticity that is directly responsible for a smaller (i.e., down-conditioned) H-reflex, while other major descending and ascending tracts are not essential (Chen and Wolpaw 1997. The cerebellum might simply be required for the normal functioning of sensorimotor cortex (SMC), or it might actually guide the CST activity that produces the spinal cord plasticity that is directly res...

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“…al, 2004;Zehr, 2006;Zehr et.al., 2007). Previous studies with the Hreflex demonstrated clearly that adaptive plasticity could be induced in the spinal cord and that it could be examined by using the H-reflex (Agaard, 2003;Carp & Wolpaw, 1994;Wolpaw & Chen, 2006). Some researchers have investigated the effectiveness of the Ia monosynaptic pathway in leg muscles in relation to the handedness.…”

Section: Neural Asymmetry Studies With the Use Of The Spinal Circuit mentioning

confidence: 99%

Paresthesias as Reflection of the Lateral Asymmetry of Neural Function in Human

Olex-Zarychta¹

2012

Paresthesia

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The cerebellum in maintenance of a motor skill: A hierarchy of brain and spinal cord plasticity underlies H-reflex conditioning

Cited by 58 publications

References 78 publications

Cortical stimulation causes long-term changes in H-reflexes and spinal motoneuron GABA receptors

Cortical stimulation causes long-term changes in H-reflexes and spinal motoneuron GABA receptors

Ablation of the inferior olive prevents H-reflex down-conditioning in rats

Paresthesias as Reflection of the Lateral Asymmetry of Neural Function in Human

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