title: Early enhancement but no late changes of motor responses induced by intracortical microstimulation in the ketamine-anesthetized rat.
abstract: The objectives of this study were to determine whether changes in electromyographic (EMG) responses observed during prolonged intracortical microstimulation (ICMS) were due to local plasticity of the motor system or to global changes in the preparation. Local effects would be expressed as changes only along the activated motor pathway, whereas global effects would be expressed as changes also appearing at distant cortical efferent microzones. The results of ICMS in the ketamine-anesthetized rat showed that the size of consecutive EMG responses increased gradually to a relatively stable magnitude over a period of four to six trains of stimuli. This early enhancement of EMG responses was maintained while continuously providing trains of stimuli at 1 Hz. However, it disappeared after a 5-min period of muscle inactivity. This response enhancement in the presence of ketamine (an NMDA, N-methyl-D-aspartate, receptor blocker) suggests that a neuronal mechanism involving non-NMDA-mediated homosynaptic short-term potentiation (STP) was responsible for the early enhancement of EMG responses. To compare ICMS effects at several time intervals it was necessary to average several evoked EMG responses because there was normal biological variability between single EMG responses. To determine the optimal number of EMG responses that would provide a reliable average EMG response, averages of 5, 10, 15, 20, and 25 EMG responses evoked from a single cortical site were collected at 5-min intervals. The results revealed that averages of 10 responses would provide reliable average EMG responses for all subsequent analyses. There were wide fluctuations in the average EMG responses when periodic injections of ketamine were used to maintain a low reflexive state in the animal. Switching to continuous infusion of ketamine abolished these fluctuations but there remained a small drift in the magnitudes of consecutive EMG responses. To test whether this drift reflected local plastic changes in the motor system induced by stimulation or some global changes, EMG responses evoked from another ICMS site were used as control. The rationale was that global effects would affect all motor output sites equally. The sizes of control EMG responses followed a similar time course to those evoked from the test site. Furthermore, standardizing the test EMG responses with respect to the control responses eliminated the drift in response magnitudes. Thus the drift was due to slow global changes in neuronal excitability possibly produced by the anesthesia. In conclusion, late changes occurring after hours of ICMS were not due to plasticity of the motor system but rather to global changes in the preparation, possibly resulting from the inability to set an ideal anesthetic infusion rate that could maintain a constant level of neuronal excitability over long periods of time. However, there was early enhancement of the EMG responses evoked by ICMS due to neuronal plasticity possibly mediated by a non-NMDA mechanism of homosynaptic STP such as post-tetanic potentiation (PTP). This early enhancement would favor recruitment of the previously activated motor pathway and lead to greater consistency in movement execution.
authors.affiliation: Department of Anatomy and Neurobiology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Gu
authors.forename: P A
authors.initials: PA
authors.lastname: Fortier
mesh_terms: D000758:Anesthesia; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004576:Electromyography; D007649:Ketamine; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D007649:Ketamine