Dataset Information

Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys.

ABSTRACT: The hypothesis of cerebellar learning proposes that complex spikes in Purkinje cells engage mechanisms of plasticity in the cerebellar cortex; in turn, changes in the cerebellum depress the simple-spike response of Purkinje cells to a given stimulus and cause the adaptive modification of a motor behavior. Many elements of this hypothesis have been supported by prior experiments, and correlations have been found [corrected] between complex spikes, simple-spike plasticity and behavior [corrected] during the learning process. We carried out a trial-by-trial analysis of Purkinje cell responses in awake-behaving monkeys and found evidence for a causal role for complex spikes in the induction of cerebellar plasticity during a simple motor learning task. We found that the presence of a complex spike on one learning trial was linked to a substantial depression of simple-spike responses on the subsequent trial, at a time when behavioral learning was expressed.

SUBMITTER: Medina JF

PROVIDER: S-EPMC2577564 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys.

Medina Javier F JF Lisberger Stephen G SG

Nature neuroscience 20080921 10

The hypothesis of cerebellar learning proposes that complex spikes in Purkinje cells engage mechanisms of plasticity in the cerebellar cortex; in turn, changes in the cerebellum depress the simple-spike response of Purkinje cells to a given stimulus and cause the adaptive modification of a motor behavior. Many elements of this hypothesis have been supported by prior experiments, and correlations have been found [corrected] between complex spikes, simple-spike plasticity and behavior [corrected] ...[more]

PMID: 18806784

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Project description:Lower limb paralysis from spinal cord injury (SCI) or neurological disease carries a poor prognosis for recovery and remains a large societal burden. Neurophysiological and neuroprosthetic research have the potential to improve quality of life for these patients; however, the lack of an ethical and sustainable nonhuman primate model for paraplegia hinders their advancement. Therefore, our multidisciplinary team developed a way to induce temporary paralysis in awake behaving macaques by creating a fully implantable lumbar epidural catheter-subcutaneous port system that enables easy and reliable targeted drug delivery for sensorimotor blockade. During treadmill walking, aliquots of 1.5% lidocaine with 1:200,000 epinephrine were percutaneously injected into the ports of three rhesus macaques while surface electromyography (EMG) recorded muscle activity from their quadriceps and gastrocnemii. Diminution of EMG amplitude, loss of voluntary leg movement, and inability to bear weight were achieved for 60-90 min in each animal, followed by a complete recovery of function. The monkeys remained alert and cooperative during the paralysis trials and continued to take food rewards, and the ports remained functional after several months. This technique will enable recording from the cortex and/or spinal cord in awake behaving nonhuman primates during the onset, maintenance, and resolution of paraplegia for the first time, thus opening the door to answering basic neurophysiological questions about the acute neurological response to spinal cord injury and recovery. It will also negate the need to permanently injure otherwise high-value research animals for certain experimental paradigms aimed at developing and testing neural interface decoding algorithms for patients with lower extremity dysfunction.NEW & NOTEWORTHY A novel implantable lumbar epidural catheter-subcutaneous port system enables targeted drug delivery and induction of temporary paraplegia in awake, behaving nonhuman primates. Three macaques displayed loss of voluntary leg movement for 60-90 min after injection of lidocaine with epinephrine, followed by a full recovery. This technique for the first time will enable ethical live recording from the proximal central nervous system during the acute onset, maintenance, and resolution of paraplegia.

Dataset Information

Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys.

Publications

Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys.

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