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

Abstract

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...

The negotiated equilibrium model of spinal cord function

“…None of CST transection, DIN ablation or IO ablation has a long-term effect on H-reflex size in naïve (i.e. unconditioned) rats (Chen et al 2001(Chen et al , 2016a. Thus, the effects in Fig.…”

“…If the IO is ablated before down‐conditioning, the H‐reflex does not decrease; if it is ablated after down‐conditioning, some of the decrease disappears over 10 days while the remainder survives for 40 days and then disappears (Chen et al . 2016 a , b ). The gradual partial loss of the H‐reflex decrease after IO ablation compared to the immediate partial loss after DIN ablation suggests that the IO guides cerebellar plasticity that survives 10 days without continued IO influence.…”

Learning New Feedforward Motor Commands Based on Feedback Responses

“…They have shown that such conditioning produces multisite changes at the level of the spinal cord that drive the observed differences in the H-reflex response, including a shift in motorneuron firing threshold [76] and a change in the number of GABAergic terminals [77]. Importantly, successful operant conditioning of the spinal cord circuit itself requires a functional corticospinal tract and sensorimotor cortex as well as the cerebellum and inferior olive but no other major ascending or descending spinal pathways [78][79][80][81][82][83][84], indicating that cerebellar contributions by the sensorimotor cortex (as opposed to the rubrospinal tract) are critical for implementing learning [80,81]. Given the differences between H-reflex operant conditioning, especially with respect to its development over weeks and months, an extremely long timescale even relative to the slow learning in our paradigm, it is unclear whether the same mechanisms are in play for the type of learning we report here.…”

Motor learning and transfer: from feedback to feedforward control

“…They have shown that such conditioning produces multisite changes at the level of the spinal cord that actually drive the observed differences in the H-reflex response, including a shift in motorneuron firing threshold (Carp and Wolpaw, 1994) and a change in the number of GABAergic terminals (Wang et al, 2006) . Importantly, successful operant conditioning of the spinal cord circuit itself requires a functional corticospinal tract and sensorimotor cortex as well as the cerebellum and inferior olive but no other major ascending or descending spinal pathways Wolpaw, 2002, 2005;Chen et al, , 2006aChen et al, , 2006bChen et al, , 2016Wolpaw and Chen, 2006) , indicating that cerebellar contributions via the sensorimotor cortex (as opposed to the rubrospinal tract) are critical for implementing the learning (Chen and Wolpaw, 2005;Wolpaw and Chen, 2006) . Given the differences between H-reflex operant conditioning, especially with respect to its development over weeks and months, an extremely long time-scale even relative to the slow learning in our paradigm, it is unclear whether the same mechanisms are in play for the type or learning we report here.…”