Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult

Recovery of motor function following stroke is believed to be supported, at least in part, by functional compensation involving residual neural tissue. The present study used a rodent model of focal ischemia and intracortical microstimulation (ICMS) to examine the behavioral and physiological effects of cortical stimulation in combination with motor rehabilitation. Adult rats were trained to criterion on a single pellet reaching task before ICMS was used to derive maps of movement representations within forelimb motor cortex contralateral to the trained paw. All animals then received a focal ischemic infarct within the motor map. A cortical surface electrode was implanted over the motor cortex. Low levels of electrical stimulation were applied during rehabilitative training on the same reaching task for 10 days and ICMS used to derive a second motor map. Results showed that both monopolar and bipolar cortical stimulation significantly enhanced motor recovery and increased the area of cortex from which microstimulation movements could be evoked. The results demonstrate the behavioral and neurophysiological benefits of cortical stimulation in combination with rehabilitation for recovery from stroke.     

Neocortical movement representations are reduced and reorganized following bilateral intrastriatal 6-hydroxydopamine infusion and dopamine type-2 receptor antagonism

The neurophysiologic model of Parkinson's disease predicts nigrostriatal dopamine depletion leads to increased inhibitory basal ganglia output resulting in frontal neocortical hypoactivity. The nature of this hypoactivation is not well understood and modeled predominantly by a unilateral representation. Intracortical microstimulation (ICMS) was used to probe topographic movement representations of the left forelimb motor area 2 weeks following sham, unilateral left hemisphere or bilateral intrastriatal 6-hydroxydopamine (6-OHDA) infusion and under acute dopamine receptor antagonism with haloperidol in non-lesioned rats. 6-OHDA infusions induced a significant loss of substantia nigra pars compacta (SNc) dopamine neurons. Bilateral SNc lesions and haloperidol significantly reduced map area which was preserved in unilateral lesions. All lesion conditions and haloperidol induced significant map reorganization, characterized by increased representation of distal forelimb movements. Results suggest basal ganglia dopamine deficiency can affect the topographic organization of sensorimotor neocortex and lead to significant reduction in the size of motor representations. We conclude that the neurophysiologic model is supported but that bilateral loss of dopamine is required to see a reduction in the size of motor maps.     

Differential neuroplastic changes in neocortical movement representations and dendritic morphology in epilepsy-prone and epilepsy-resistant rat strains following high-frequency stimulation

The epileptogenic-prone (FAST) and epileptogenic-resistant (SLOW) rat strains have become a valuable tool for investigating the neurochemical and neurophysiological basis of epilepsy. This study examined the two strains with respect to their neocortical movement representations and cortical layer III pyramidal cell dendritic morphology in both control and potentiated conditions. FAST and SLOW rats received high-frequency stimulation of the corpus callosum in order to induce long-term polysynaptic potentiation of the transcallosal pathway to the sensorimotor neocortex. Baseline-evoked potentials of this pathway were recorded in the left hemisphere before stimulation, and following 5, 10, 15 and 20 days of high-frequency stimulation. All rats then underwent high-resolution intracortical microstimulation (ICMS) in order to assess functional movement representations of the left caudal forelimb area of the sensorimotor cortex. Immediately following ICMS, the brains were stained with the Golgi-Cox method, and the length, branching and spine density of frontal and occipital neocortical layer III pyramidal neurons were measured. We observed that high-frequency stimulation induced similar increases in polysynaptic potentiation in both rat strains; however, only the FAST strain showed an increase (doubling) in the size of their motor maps. We also observed decreases in dendritic length and branching in the FAST rats, and the opposite profile in the SLOW rats. The potentiated FAST rats also showed an increase in spine density. Our results suggest that differences in susceptibility to epileptogenesis may result in a differential response to stimulation-induced plasticity.     

Intact intracortical microstimulation (ICMS) representations of rostral and caudal forelimb areas in rats with quinolinic acid lesions of the medial or lateral caudate-putamen in an animal model of Huntington's disease

Neurotoxic, cell-specific lesions of the rat caudate-putamen (CPu) have been proposed as a model of human Huntington's disease and as such impair performance on many motor tasks, including skilled forelimbs tasks such as reaching for food. Because the CPu and motor cortex share reciprocal connections, it has been proposed that the motor deficits are due in part to a secondary disruption of motor cortex. The purpose of the present study was to examine the functionality of the motor cortex using intracortical microstimulation (ICMS) following neurotoxic lesions of the CPu. ICMS maps have been shown to be sensitive indicators of motor skill, cortical injury, learning, and experience. Long-evans hooded rats received a sham, a medial, or a lateral CPu lesion using the neurotoxin, quinolinic acid (2,3-pyridinedicarboxylic acid). Two weeks later the motor cortex was stimulated under light ketamine anesthesia. Neither lateral nor medial lesions of the CPu altered the stimulation threshold for eliciting forelimb movements, the type of movements elicited, or the size of the rostral forelimb (RFA) and caudal forelimb areas (CFA) from which movements were elicited. The preservation of ICMS forelimb movement representations (the forelimb map) in rats with cell-specific CPu lesions suggests motor impairments following lesions of the lateral striatum are not due to the disruption of the motor map. Therefore, the impairments that follow striatal cell loss are due either to alterations in circuitry that is independent of motor cortex or to alterations in circuitry afferent to the motor cortex projections.     

A prolonged experimental febrile seizure results in motor map reorganization in adulthood

IntroductionClinical studies have suggested that children experiencing a febrile seizure (FS) before the age of 1 year have persistent deficits, but it is unknown whether these seizures lead to permanent cortical reorganization and alterations in function. A FS on the background of increased genetic seizure susceptibility may also lead to negative long-term consequences. Alterations in neocortical motor map expression provide a measure of neocortical reorganization and have been reported in both adults with frontal lobe epilepsy and following seizure induction in experimental models. The objectives of the present study were to determine whether 1) an infantile FS leads to changes to motor map expression in adulthood; 2) long-term cortical reorganization is a function of the age at FS or genetic seizure susceptibility; and 3) different levels of GABA_A or glutamate receptor subunits or cation-chloride-co-transporters (CCCs) at the time of FS correlate with alterations to motor map expression.Materials and methodsFSs were induced in postnatal day 10 (P10) or P14 Long–Evans (LE) rats or in P14 seizure-prone FAST rats by the administration of the bacterial endotoxin lipopolysaccharide (LPS) and a subconvulsant dose of kainic acid. Ten weeks later intracortical microstimulation was performed to generate motor maps of forelimb movement representations. Sensorimotor neocortex samples were also dissected from naïve P10 FAST and P10 and P14 LE pups for western blotting with antibodies against various GABA_A, NMDA, and AMPA receptor subunits and for CCCs.ResultsAdult FAST rats had larger motor maps with lower stimulation thresholds after a FS at P14, while adult LE rats had significantly lower map stimulation thresholds but similar sized maps after a FS at P10 compared to controls. There were no differences in neocortical motor map size or stimulation thresholds in adult LE rats after a FS at P14. Both P10 LE and P14 FAST rats had significantly lower levels of the GABA_A receptor α1 subunit, higher levels of the α2 subunit, and a higher NKCC1/KCC2 ratio in the sensorimotor cortex compared with the P14 LE rat. In addition, the P14 FAST rats had lower levels of the GluR2 and NR2A receptor subunits in the sensorimotor cortex compared with the P14 LE rats.ConclusionsA single infantile FS can have long-term effects on neocortical reorganization in younger individuals and those with underlying seizure susceptibility. These changes may be related to an increased level of excitability in the neocortex of younger or genetically seizure-prone rats, as suggested by immaturity of their GABAergic and CCC systems. Given the high incidence of FSs in children, it will be important to gain a better understanding of how age and genetic seizure predisposition may contribute to the long-term sequelae of these events.     

Hippocampal kindling leads to motor map expansion

Summary:  Purpose: To determine whether seizure activity, repeatedly elicited in the hippocampus, could alter the functional organization of neocortical movement representations (motor maps) and whether a relation exists between the number of afterdischarges recorded in the sensorimotor neocortex and the size of the motor maps.
Methods: We electrically kindled the right ventral hippocampus of Long–Evans hooded rats, twice daily, for 40 sessions and recorded the afterdischarges in the stimulated hippocampus and right sensorimotor neocortex. Between 3 and 7 days after the last seizure, we used high-resolution intracortical microstimulation to derive the forelimb-movement representations in the left (un-implanted) sensorimotor neocortex.
Results: In the hippocampal kindled rats, we observed a dramatic expansion of the area of neocortex that would elicit forelimb movements compared with sham-kindled controls. The number of afterdischarges recorded in the neocortex was significantly and positively correlated with the size of the motor maps.
Conclusions: Seizures propagating from the hippocampus have long-distance effects on the functional organization of motor maps.     

Preserved ipsilateral-to-lesion motor map organization in the unilateral 6-OHDA-treated rat model of Parkinson's disease

The classic view of dopamine (DA) loss in Parkinson's disease is that it produces a functional deafferentation in striatal-cortical circuitry that, in turn, contributes to sensorimotor deficits. The present study examines this view in the rat by assessing how DA-depletion affects the intracortical microstimulation (ICMS) topographic representation of movement in the rostral and caudal motor areas of the motor cortex. The ICMS map is used as an index of motor cortex function because it has been shown to reflect motor function and experience. Groups of rats received no training or skilled reach training and were then given unilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the nigrostriatal bundle to deplete nigrostriatal DA. Lesion success was confirmed by abnormalities in skilled reaching, by apomorphine-induced rotation, and by loss of DA neurons in the substantia nigra. The size and threshold of the motor map in naive and skilled reach trained DA-depleted rats were preserved. In addition, there was an increase in distal limb representation in the caudal forelimb area (CFA) in the DA-depleted rats suggesting a possible plastic response to the behavioral effects of DA-depletion. The presence of preserved size and modified map organization in DA-depleted rats is discussed in relation to the hypothesis that preserved motor cortex functionality despite DA loss underlies the spared motor abilities of DA-depleted rats.     

Larger cortical motor maps after seizures

Expansion of motor maps occurs in both clinical populations with epilepsy and in experimental models of epilepsy when the frontal lobes are involved. We have previously shown that the forelimb area of the motor cortex undergoes extensive enlargement after seizures, although the extent to which many movement representation areas are altered is not clear. Here we hypothesize that movement representations in addition to the forelimb area will be enlarged after cortical seizures. To test our hypotheses, Long Evans Hooded rats received 20 sessions of callosal (or sham) kindling, and then were subjected to intracortical microstimulation to map several movement representations including the jaw, neck, forelimb, hindlimb, trunk and tail. We found significantly larger total map areas of several movement representations, including movements that could be evoked more posterior than they are in control rats. We also show the presence of more multiple movement sites and lower movement thresholds in kindled rats, suggesting that movements not only overlap and share cortical territory after seizures, but become present in formerly non-responsive sites as they become detectable with our intracortical microstimulation methodology. In summary, several motor map areas become larger after seizures, which may contribute to the interictal motor disturbances that have been documented in patients with epilepsy.     

Motor map expansion in the pilocarpine model of temporal lobe epilepsy is dependent on seizure severity and rat strain

Functional alterations in movement representations (motor maps) have been observed in some people with epilepsy and, under experimental control, electrically-kindled seizures in rats also result in persistently larger motor maps. To determine if a single event of status epilepticus and its latent consequences can affect motor map expression, we assessed forelimb motor maps in rats using the pilocarpine model of temporal lobe epilepsy. We examined both pilocarpine-induced seizures, and status epilepticus (SE) in two strains that differ in their propensity for epileptogenesis; Wistar and Long-Evans. Pilocarpine was administered intraperitoneally at dosages that resulted in equivalent proportions of seizures, SE, and survival in both strains. Rats from both strains were given saline injections as a control. Diazepam was administered to all rats to attenuate seizure activity and promote survival. All rats had high-resolution movement representations derived using standard intracortical microstimulation methodologies at 48 h, 1 week, or 3 weeks following treatment. Pilocarpine-induced seizures only gave rise to motor map enlargement in Wistar rats, which also showed interictal spiking, and only at 3 weeks post-treatment indicating altered motor map expression in this strain following a latent or maturational period. Pilocarpine-induced SE yielded larger motor maps at all time points in Wistar rats but only a transient (48 h) map expansion in Long-Evans rats. Our results demonstrate that seizures and SE induced by a convulsant agent alter the functional expression of motor maps that is dependent on seizure severity and a genetic (strain) predisposition to develop epileptiform events.     

Limits on recovery in the corticospinal tract of the rat: partial lesions impair skilled reaching and the topographic representation of the forelimb in motor cortex

Although evidence suggests that there are impairments in skilled movements following very large lesions of the pyramidal component of the corticospinal tract, the behavioral and electrophysiological effects of partial lesion has not received equal attention. Here, rats with complete lesions or partial lesions (medial, central, or lateral third) of the pyramidal tract at the medullary pyramids were evaluated for their quantitative and qualitative postsurgical performance on a skilled reaching task, following which the topographic representation of their forelimb was mapped with intracortical microstimulation (ICMS). Complete lesions impaired reaching success, impaired the qualitative features of reaching movements, and abolished ICMS evoked movement from the forelimb region of motor cortex. Although partial lesions did not impair reaching success, they did impair qualitative aspects of limb movement including forepaw aiming, supination, and food pellet release. ICMS indicated a reduction in the size of the forelimb area, especially the distal area of the caudal forelimb area (CFA), of the motor map. The behavioral and electrophysiological impairments did not vary with lesion location within the pyramidal tract. The incomplete recovery, as measured both behaviorally and electrophysiologically, demonstrates that plasticity within the corticospinal system is limited even with lesions that permit substantial sparing of pyramidal tract fibers.     

High frequency stimulation of the subthalamic nucleus acutely rescues motor deficits and neocortical movement representations following 6-hydroxydopamine administration in rats

Loss of frontal neocortical activation is one of the main neurophysiological abnormalities of Parkinson's disease (PD) and can be observed in rodent models of nigrostriatal degeneration. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus improves motor deficits in PD. However, it is unknown whether this general therapeutic effect is associated with a restoration of frontal output function. To address this question, chronic stimulating electrodes were implanted bilaterally into the subthalamic nuclei of adult rats that received either bilateral intrastriatal 6-hydroxydopamine (6-OHDA) or vehicle infusion to induce nigrostriatal degeneration. Forelimb use and locomotor activity were assessed based on the cylinder and open field tests in intact, post-lesion + sham DBS, and post-lesion + DBS conditions. Intracortical microstimulation was then used to probe frontal output function of forelimb motor areas. DBS was found to improve motor deficits arising from 6-OHDA lesions, increase forelimb map area, and decrease movement thresholds relative to baseline. These effects were significantly greater in 6-OHDA lesion rats compared to vehicle controls. Results indicate that changes in motor map expression can take place during subthalamic DBS following dopamine depletion in a rodent model of PD.     

Hindlimb unloading affects cortical motor maps and decreases corticospinal excitability

A chronic reduction in neuromuscular activity through prolonged body immobilization of humans results in muscle atrophy and weakness as well as motor tasks performance impairment, which is correlated to a change in corticospinal excitability. In rats, hindlimb unloading (HU) is commonly used to mimic the effects of confinement to bed in patients. Several studies have reported changes in the representation of the somatosensory cortex in rodents submitted to HU or sensorimotor restriction by casting: remapping and enlargement of receptive fields, changes in the response of layer 4 neurons to peripheral stimulation. However, we have no data about motor cortical maps in rats submitted to a period of motor restriction during adulthood. Therefore, the objectives of the present study were twofold: to determine, in control rats and in rats submitted to a 14-day period of HU, the size and organization of hindlimb representation in the M1 cortex and to evaluate the overall excitability of M1 cortex by determining the stimulation thresholds. HU led to a dramatic decrease in the hindlimb representation on the M1 cortex (-61%, p<0.01). In addition, current thresholds for eliciting a movement were increased. The toes were less strongly affected by HU than other joint. Our main conclusion is that HU dramatically affects the organization and functioning of cortical motor maps and decreases corticospinal excitability.     

Long-Evans rats have a larger cortical topographic representation of movement than Fischer-344 rats: a microstimulation study of motor cortex in naïve and skilled reaching-trained rats

Intracortical microstimulation of the frontal cortex evokes movements in the contralateral limbs, paws, and digits of placental mammals including the laboratory rat. The topographic representation of movement in the rat consists of a rostral forelimb area (RFA), a caudal forelimb area (CFA), and a hind limb area (HLA). The size of these representations can vary between individual animals and the proportional representation of the body parts within regions can also change as a function of experience. To date, there have been no investigations of strain differences in the cortical map of rats, and this was the objective of the present investigation. The effect of cortical stimulation was compared in young male Long-Evans rats and Fischer-344 rats. The overall size of the motor cortex representation was greater in Long-Evans rats compared to Fischer-344 rats and the threshold required to elicit a movement was higher in the Fischer-344 rats. An additional set of animals were trained in a skilled reaching task to rule out the possibility that experiential differences in the groups could account for the result and to examine the relationship between the differences in topography of cortical movement representations and motor performance. The Long-Evans rats were quantitatively and qualitatively better in skilled reaching than the Fischer-344 rats. Also, Long-Evans rats exhibited a relatively larger area of the topographic representation and lower thresholds for eliciting movement in the contralateral forelimb. This is the first study to describe pronounced strain-related differences in the microstimulation-topographic map of the motor cortex. The results are discussed in relation to using strain differences as a way of examining the behavioral, the physiological, and the anatomical organization of the motor system.     

Corticospinal control of antagonistic muscles in the cat

We recently suggested that movement-related inter-joint muscle synergies are recruited by selected excitation and selected release from inhibition of cortical points. Here we asked whether a similar cortical mechanism operates in the functional linking of antagonistic muscles. To this end experiments were done on ketamine-anesthetized cats. Intracortical microstimulation (ICMS) and intramuscular electromyographic recordings were used to find and characterize wrist, elbow and shoulder antagonistic motor cortical points. Simultaneous ICMS applied at two cortical points, each evoking activity in one of a pair of antagonistic muscles, produced co-contraction of antagonistic muscle pairs. However, we found an obvious asymmetry in the strength of reciprocal inhibition; it was always significantly stronger on physiological extensors than flexors. Following intravenous injection of a single bolus of strychnine, a cortical point at which only a physiological flexor was previously activated also elicited simultaneous activation of its antagonist. This demonstrates that antagonistic corticospinal neurons are closely grouped, or intermingled. To test whether releasing a cortical point from inhibition allows it to be functionally linked with an antagonistic cortical point, one of three GABA(A) receptor antagonists, bicuculline, gabazine or picrotoxin, was injected iontophoretically at one cortical point while stimulation was applied to an antagonistic cortical point. This coupling always resulted in co-contraction of the represented antagonistic muscles. Thus, antagonistic motor cortical points are linked by excitatory intracortical connections held in check by local GABAergic inhibition, with reciprocal inhibition occurring at the spinal level. Importantly, the asymmetry of cortically mediated reciprocal inhibition would appear significantly to bias muscle maps obtained by ICMS in favor of physiological flexors.     

Developmental and Interventional Plasticity of Motor Maps after Perinatal Stroke

Within the perinatal stroke field, there is a need to establish preclinical models where putative biomarkers for motor function can be examined. In a mouse model of perinatal stroke, we evaluated motor map size and movement latency following optogenetic cortical stimulation against three factors of post-stroke biomarker utility: (1) correlation to chronic impairment on a behavioral test battery; (2) amenability to change using a skilled motor training paradigm; and (3) ability to distinguish individuals with potential to respond well to training. Thy1-ChR2-YFP mice received a photothrombotic stroke at postnatal day 7 and were evaluated on a battery of motor tests between days 59 and 70. Following a cranial window implant, mice underwent longitudinal optogenetic motor mapping both before and after 3 weeks of skilled forelimb training. Map size and movement latency of both hemispheres were positively correlated with impaired spontaneous forelimb use, whereas only ipsilesional hemisphere map size was correlated with performance in skilled reaching. Map size and movement latency did not show groupwise changes with training; however, mice with the smallest pretraining map sizes and worst impairments demonstrated the greatest expansion of map size in response to skilled forelimb training. Overall, motor map size showed utility as a potential biomarker for impairment and training-induced modulation in specific individuals. Future assessment of the predictive capacity of post-stroke motor representations for behavioral outcome in animal models opens the possibility of dissecting how plasticity mechanisms contribute to recovery following perinatal stroke.SIGNIFICANCE STATEMENT We investigated the utility of two cortical motor representation measures (motor map size and movement onset latency) as potential biomarkers for post-stroke motor recovery in a mouse model of perinatal stroke. Both motor map size and movement latency were associated with functional recovery after perinatal stroke, with map size showing an additional association between training responsiveness and severity of impairment. Overall, both motor map size and movement onset latency show potential as neurophysiological correlates of recovery. As such, future studies of perinatal stroke rehabilitation and neuromodulation should include these measures to help explain neurophysiological changes that might be occurring in response to treatment.     

Time course of motor cortex reorganization following botulinum toxin injection into the vibrissal pad of the adult rat

The present experiment studies representation patterns in the motor cortex (M1) of adult rats, 1, 3, 6, and 12 days after unilateral injection of Botulinum Toxin (BTX) into the vibrissa pad. Intracortical microstimulation (ICMS) was used to evidence changes in the representation over time and in the current thresholds required to evoke movements inside the disconnected vibrissa region. After 1 day, isolated as well as contiguous negative sites were observed within the motor cortex corresponding to the disconnected vibrissa region. Thereafter the percentage of unresponsive sites decreased so that after 6 days, the number of unresponsive sites was not significantly higher than those in the control hemispheres. Within the disconnected vibrissa region, electrical stimulation elicited forelimb, eye, ipsilateral vibrissa and neck movements. Following BTX injection, the enlargement of the forelimb representation into the disconnected vibrissa representation began during the first day and stabilized during the second week after injection. In the first days, stimulation thresholds in expanded forelimb sites were higher than those required for similar movement in normal M1 forelimb representation. These thresholds then declined so that in approximately 6 days they were similar to normal. There was no clear evidence that stimulation of sites in the medial part of disconnected vibrissa-cortex evoked eye movements during the first 6 days after BTX injection. After this time, thresholds required to evoke eye movement in expanded sites were generally similar to, and never higher than, those needed to evoke this movement in control sites. Intermingled ipsilateral vibrissa and neck movement occupies part of the medial vibrissa region. Over the 12 days, extension of the ipsilateral vibrissa representation shrank while the representation of neck movement remained unchanged. Throughout the entire time there was no change in the excitability of these sites and the thresholds remained higher than that needed to elicit the vibrissa movement normally represented in this cortical region. No significant differences in threshold were found over time for any of the other movement categories represented in M1. These results indicate that, over time, the new movements inside the disconnected vibrissa region develop differently in M1 following peripheral motor disconnection. The implications for mechanisms involved in cortical plasticity are discussed.     

Whisker motor cortex reorganization after superior colliculus output suppression in adult rats

The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS‐evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1–3 weeks). The ICMS‐evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS‐evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short‐term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS‐evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour.     

Suppression of activity in the forelimb motor cortex temporarily enlarges forelimb representation in the homotopic cortex in adult rats

After forelimb motor cortex (FMC) damage, the unaffected homotopic motor cortex showed plastic changes. The present experiments were designed to clarify the electrophysiological nature of these interhemispheric effects. To this end, the output reorganization of the FMC was investigated after homotopic area activity was suppressed in adult rats. FMC output was compared after lidocaine-induced inactivation (L-group) or quinolinic acid-induced lesion (Q-group) of the contralateral homotopic cortex. In the Q-group of animals, FMC mapping was performed, respectively, 3 days (Q3D group) and 2 weeks (Q2W group) after cortical lesion. In each animal, FMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). The findings demonstrated that in the L-group, the size of forelimb representation was 42.2% higher than in the control group ( P  < 0.0001). The percentage of dual forelimb–vibrissa movement sites significantly increased over the controls ( P  < 0.0005). The dual-movement sites occupied a strip of the map along the rostrocaudal border between the forelimb and vibrissa representations. This form of interhemispheric diaschisis had completely reversed, with the recovery of the baseline map, 3 days after the lesion in the contralateral FMC. This restored forelimb map showed no ICMS-induced changes 2 weeks after the lesion in the contralateral FMC. The present results suggest that the FMCs in the two hemispheres interact continuously through predominantly inhibitory influences that preserve the forelimb representation and the border vs. vibrissa representation.     

Plastic changes in the vibrissa motor cortex in adult rats after output suppression in the homotopic cortex

After motor cortex damage, the unaffected homotopic cortex shows changes in motor output. The present experiments were designed to clarify the nature of these interhemispheric effects. We investigate the vibrissa motor cortex (VMC) output after activity suppression of the homotopic area in adult rats. Comparison was made of VMC output after lidocaine inactivation (L-group) or quinolinic acid lesion (Q-group) of the homotopic cortex. In the Q-group, VMC mapping was performed 3 days (Q3Ds group), 2 weeks (Q2Ws group) and 4 weeks (Q4Ws group) after cortical lesion. In each animal, VMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere ipsilateral and contralateral to injections). Findings demonstrated that, in the L-group, the size of vibrissal representation was 39.5% smaller and thresholds required to evoke vibrissa movement were 46.3% higher than those in the Control group. There was an increase in the percentage of ineffective sites within the medial part of the VMC and an increase in the percentage of forelimb sites within the lateral part. Both the Q3Ds group and the L-group led to a similar VMC reorganization (Q3Ds vs. L-group, P > 0.05). In the Q2Ws group the VMC representation showed improvement in size (83.4% recovery compared with controls). The VMC showed recovery to normal output at 4 weeks after lesion (Control vs. Q4Ws group, P > 0.05). These results suggest that the VMC of the two hemispheres continuously interact through excitatory influences, preserving the normal output and inhibitory influences defining the border with the forelimb representation.     

Overlapping representations of the neck and whiskers in the rat motor cortex revealed by mapping at different anaesthetic depths

The primary motor cortex of mammals has an orderly representation of different body parts. Within the representation of each body part the organization is more complex, with groups of neurons representing movements of a muscle or a group of muscles. In rats, uncertainties continue to exist regarding organization of the primary motor cortex in the whisker and the neck region. Using intracortical microstimulation (ICMS) we show that movements evoked in the whisker and the neck region of the rat motor cortex are highly sensitive to the depth of anaesthesia. At light anaesthetic depth, whisker movements are readily evoked from a large medial region of the motor cortex. Lateral to this is a small region where movements of the neck are evoked. However, in animals under deep anaesthesia whisker movements cannot be evoked. Instead, neck movements are evoked from this region. The neck movement region thus becomes greatly expanded. An analysis of the threshold currents required to evoke movements at different anaesthetic depths reveals that the caudal portion of the whisker region has dual representation, of both the whisker and the neck movements. The results also underline the importance of carefully controlling the depth of anaesthesia during ICMS experiments.