Pyramidal Tract Neurons Research Articles

Physical practice induces excitability changes in human hand motor area during motor imagery

The present study was undertaken to investigate the effects of physical practice on excitability changes in human primary motor cortex (M1) during motor imagery (MI). Using different intensities of transcranial magnetic stimulation (TMS), we examined changes in the motor evoked potential (MEP) of the first dorsal interosseous (FDI) muscle with and without MI, and before and after physical practice. On comparing results for MEPs recorded before and after physical practice, the difference between the MEP amplitudes observed at rest and during MI only increased at higher TMS intensities. This finding indicates a physical practice-dependent increase of the higher threshold recruitment of corticospinal tract neurons (CTNs), consistent with synchronization for efficient movement, and provides evidence that neural mechanisms of MI depend not only on the type of movement but also on the extent of the motor adaptation (the physical practice). These present findings also show the benefit of MI and highlight beneficial neural mechanisms related to the activation of M1 during MI. In other words, MI may reflect functional changes of M1 that are similar to the changes observed after physical practice.

RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long‐lasting specific changes following spinal cord injury

Inhibition of RhoA has been shown to enhance axonal regeneration following spinal cord injury. Here we mapped mRNA expression patterns of RhoA, B, and C, Rac1, Cdc42, and Tc10 in spinal cord, sensory ganglia, and sensorimotor cortex in uninjured rats, and following spinal cord injury or sham laminectomy. In the intact spinal cord, neurons displayed high levels of Rac1, Cdc42, and Tc10 mRNA hybridization signal. GFAP-immunoreactive astrocytes expressed primarily RhoB and Rac1, while oligodendrocyte-like cells expressed RhoA, Rac1, and Cdc42. Injury caused profound, long-lasting upregulation of RhoA, Rac1, Cdc42, and Tc10 mRNA in the spinal cord, while RhoB was modestly increased and RhoC did not change. GFAP-immunoreactive reactive astrocytes exhibited a dramatic increase of RhoA mRNA expression along with increases of Rac1 and Cdc42. Injury also led to elevation of RhoA, Cdc42, and Tc10 in neurons and modest increases of RhoA, Rac1, and Tc10 in oligodendrocyte-like cells. Laminectomy caused similar, but less pronounced alterations of investigated mRNA species. In dorsal root ganglia neuronal RhoA, Rac1, Cdc42, and Tc10 mRNA levels were increased similarly by spinal cord injury and sham surgery. The CST pyramidal cells expressed Tc10 mRNA and the CST itself was Tc10-immunoreactive. Tc10-immunoreactivity disappeared distal to injury. We conclude that there are gene-specific patterns of expression of the six different Rho-GTPases in normal spinal cord and dorsal root ganglia, and that specific changes of temporal and spatial expression patterns occur in response to spinal cord injury, suggesting different roles of these GTPases in the cellular sequelae of CNS injury.

Activity of Pyramidal Tract Neurons in the Cat During Postural Corrections

The dorsal side-up body orientation in quadrupeds is maintained by a postural control system. We investigated participation of the motor cortex in this system by recording activity of pyramidal tract neurons (PTNs) from limb representations of the motor cortex during postural corrections. The cat was standing on the platform periodically tilting in the frontal plane, and maintained equilibrium at different body configurations: with the head directed forward (symmetrically alternating loading of the left and right fore limbs), or with the head voluntary turned to the right or to the left (asymmetrical loading). We found that postural corrective responses to tilts included an increase of the contact forces and activity of limb extensors on the side moving down, and their decrease on the opposite side. The activity of PTNs was strongly modulated in relation to the tilt cycle. Phases of activity of individual PTNs were distributed over the cycle. Thus the cortical output mediated by PTNs appeared closely related to a highly automatic motor activity, the maintenance of the body posture. An asymmetrical loading of limbs, caused by head turns, resulted in the corresponding changes of motor responses to tilts. These voluntary postural modifications were also well reflected in the PTNs' activity. The activity of a part of PTNs correlated well with contact forces, in some others with the limb muscle activity; in still others no correlation with these variables was observed. This heterogeneity of the PTNs population suggests a different functional role of individual PTNs.

Modulations of input-output properties of corticospinal tract neurons by repetitive dynamic index finger abductions

The goal of this study was to investigate how corticospinal tract neurons (CTNs) are modulated after repetitive dynamic muscle contractions. To address this question, changes of motor evoked potentials (MEPs) to transcranial magnetic stimulation and background EMG (B.EMG) activities were examined. Subjects were instructed to perform an isometric dynamic index finger abduction as accurately as possible under the target-force-matching tasks (10% or 30% MVC), while MEPs of a first dorsal interosseous (FDI) were elicited during performance of the task. After repetitive dynamic FDI contractions (100 trials), the following remarkable phenomena were observed: (1) both B.EMG activities and MEP amplitudes decreased in proportion to the number of trials, (2) these phenomena were most commonly observed in different conditions, i.e., different force levels and hands (preferred or non-preferred hands), and (3) after repetition of the tasks, the MEP amplitude/B.EMG (MEP/B.EMG) ratio became smaller. Decreases of B.EMG activities with reduction of MEP amplitudes and diminishing MEP/B.EMG ratio might suggest the occurrence of reorganization of input-output properties in CTNs for an efficient performance as a function of motor adaptation. Thus, we conclude that motor adaptation after repetitive dynamic muscle contractions probably occurs less specifically and due to susceptible modulations of spinal motoneurons reflected in the integrative functions of CTNs.

Ipsilateral actions of feline corticospinal tract neurons on limb motoneurons.

Contralateral pyramidal tract (PT) neurons arising in the primary motor cortex are the major route through which volitional limb movements are controlled. However, the contralateral hemiparesis that follows PT neuron injury on one side may be counteracted by ipsilateral of actions of PT neurons from the undamaged side. To investigate the spinal relays through which PT neurons may influence ipsilateral motoneurons, we analyzed the synaptic actions evoked by stimulation of the ipsilateral pyramid on hindlimb motoneurons after transecting the descending fibers of the contralateral PT at a low thoracic level. The results show that ipsilateral PT neurons can affect limb motoneurons trisynaptically by activating contralaterally descending reticulospinal neurons, which in turn activate spinal commissural interneurons that project back across to motoneurons ipsilateral to the stimulated pyramidal tract. Stimulation of the pyramids alone did not evoke synaptic actions in motoneurons but potently facilitated disynaptic EPSPs and IPSPs evoked by stimulation of reticulospinal tract fibers in the medial longitudinal fascicle. In parallel with this double-crossed pathway, corticospinal neurons could also evoke ipsilateral actions via ipsilateral descending reticulospinal tract fibers, acting through ipsilaterally located spinal interneurons. Because the actions mediated by commissural interneurons were found to be stronger than those of ipsilateral premotor interneurons, the study leads to the conclusion that ipsilateral actions of corticospinal neurons via commissural interneurons may provide a better opportunity for recovery of function in hemiparesis produced by corticospinal tract injury.

Post-spike distance-to-threshold trajectories of neurones in monkey motor cortex.

A recently developed method permits calculation of the post-spike distance-to-threshold trajectory from an extracellularly recorded spontaneous spike train, using a transform of the interspike interval histogram. We applied this method to 61 single neurones recorded from the primary motor cortex of an awake behaving monkey; 39 cells were antidromically identified as pyramidal tract neurones (PTNs). The cells fell into three categories. Fifty-three trajectories (37 from PTNs) had statistically significant peaks 10-60 ms after the preceding spike. Six neurones (2 PTNs) had non-peaked trajectories which rose exponentially towards threshold. Two cells (both unidentified) had trajectories which declined monotonically away from threshold with increasing post-spike latency. The peaked trajectories were unlikely simply to be an artefact of changing firing rate, which potentially can invalidate this method. Firstly, computer simulations confirmed that the method could accurately re-create both exponential and peaked trajectories, even in the presence of the same rate modulation as seen experimentally. Secondly, the responses of eight cells to weak single pulse intracortical microstimulation (20 microA) through a nearby electrode were measured. For each cell, including representatives of all three trajectory shapes, the modulation of response probability with post-spike latency was consistent with the trajectory computed from the spontaneous discharge. We also demonstrated that cells showed a peaked trajectory during periods with either high or low spontaneous network oscillations, so that the peaks were likely to be generated in part by single cell properties rather than exclusively by network activity. We conclude that many single neurones in motor cortex have an increased probability of firing a spike around 30 ms after the previous action potential. This could act to enhance synchronized oscillatory discharge among populations of cells at functionally relevant frequencies.

Cortical involvement in the recruitment of wrist muscles.

In executing a voluntary movement, one is faced with the problem of translating a specification of the movement in task space (e.g., a visual goal) into a muscle-recruitment pattern. Among many brain regions, the primary motor cortex (MI) plays a prominent role in the specification of movements. In what coordinate frame MI represents movement has been a topic of considerable debate. In a two-dimensional wrist step-tracking experiment, Kakei et al. described some MI cells as encoding movement in a muscle-coordinate frame and other cells as encoding movement in an extrinsic-coordinate frame. This result was interpreted as evidence for a cascade of transformations within MI from an extrinsic representation of movement to a muscle-like representation. However, we present a model that demonstrates that, given a realistic extrinsic-like representation of movement, a simple linear network is capable of representing the transformation from an extrinsic space to the muscle-recruitment patterns implementing the movements on which Kakei et al. focused. This suggests that cells exhibiting extrinsic-like qualities can be involved in the direct recruitment of spinal motor neurons. These results call into question models that presume a serial cascade of transformations terminating with MI pyramidal tract neurons that vary their activation exclusively with muscle activity. Further analysis of the model shows that the correlation between the activity of an MI neuron and a muscle does not predict the strength of the connection between the MI neuron and muscle. This result cautions against the use of correlation methods as a measure of cellular connectivity.

Synchronization in monkey motor cortex during a precision grip task. II. effect of oscillatory activity on corticospinal output.

Recordings from primary motor cortex (M1) during periods of steady contraction show oscillatory activity; these oscillations are coherent with the activity of contralateral muscles. We investigated synchronization of corticospinal output neurons with the oscillations, which could provide the pathway for their transmission to the spinal motoneurons. One hundred seventy-six antidromically identified pyramidal tract neurons (PTNs) were recorded from M1 in three macaque monkeys trained to perform a precision grip task. Local field potentials (LFP) were simultaneously recorded. All analysis was confined to the hold period of the task, where our previous work has shown that there is the strongest oscillatory activity. Coherence was calculated between LFP and PTN discharge. Significant coherence was seen in three bands, with frequencies of 10-14, 17-31, and 34-44 Hz. Coherence values were low, with the majority of PTN-LFP coherences having a peak lower than 0.05. The phase of coherence was approximately -pi/2 radians for each band (with LFP polarity defined as negative upward), although there was some dispersion of phase across the population of PTNs. Coherence was also calculated between pairs of PTNs that had been simultaneously recorded. Where there was significant coherence, it was also generally smaller than 0.05. The phase of PTN-PTN coherence clustered around zero radians. A computer model was constructed to assist the interpretation of the experimental results. It simulated an integrate-and-fire neuron responding to synaptic inputs. A fraction of the synaptic inputs was synchronized with a simulated LFP; the remainder were uncorrelated with it. The model showed that coherence between the LFP and the output spike train considerably underestimated the fraction of synchronized inputs. Additionally, for a given fraction of synchronized inputs, coherence was smaller for high- compared with low-frequency bins. Cell discharge rate also influenced the spike-LFP coherence: coherence was higher for simulations in which the cell discharged at a faster rate. Thus although levels of PTN-LFP coherence seen experimentally were low, a considerable proportion of the input to the PTN must be synchronized with the global oscillatory activity recorded by the LFP. The low LFP-PTN coherences do however indicate that cortical oscillations are transmitted with only low fidelity in the discharge of a single PTN. Using further computer simulations, it was demonstrated that a small population of PTNs could encode the cortical oscillatory signal effectively, since the action of averaging across the population improves the signal:noise ratio. The oscillations will therefore be effectively transmitted to spinal motoneurons, and this has important consequences for the possible role of oscillations in motor control of the hand.

Retrograde labeling of mouse spinal descending tracts by a recombinant adenovirus.

The present study tested whether a gene-transfer based upon the retrograde axonal transport of the lacZ adenovirus is effective in the spinal descending tracts of the adult mouse. A small volume of a replication-defective recombinant adenovirus encoding E. coli beta-galactosidase was injected into the upper lumbar cord, and, seven days later, the mice were transcardially perfused by a fixative solution. X-gal staining of coronal or sagittal sections of the spinal cord and the brain revealed that many sites of origin for rubrospinal, vestibulospinal, and reticulospinal tracts were retrogradely labeled, whereas few of the corticospinal tract neurons were retrogradely labeled. Ependymal cells surrounding the central canal of the spinal cord, which were located far from the injection site, showed a high expression of beta-galactosidase activity. Motoneurons around the injection site were strongly stained by X-gal staining, and their axons in the ventral root were anterogradely labeled. Afferent fibers in the dorsal root were labeled by the transganglionic transport of beta-galactosidase. To examine the efficacy of the uptake and retrograde transport of HRP and adenovirus, we injected a mixed solution of 10% HRP and recombinant adenovirus. The number of HRP-labeled corticospinal neurons overwhelmed the number of X-gal stained ones, while the numbers of HRP-labeled rubrospinal and subcoeruleus-spinal neurons were smaller in comparison with the numbers of beta-galactosidase-positive counterparts. The present study revealed that the origins for the spinal descending tracts except for corticospinal neurons could be efficiently gene-transferred by the retrograde infection of a recombinant adenovirus. Such a difference in efficacy of retrograde infection among the spinal descending tracts is practically important when an adenovirus-mediated gene transfer is designed to treat certain neurological diseases affecting the spinal descending tracts.

Influence of dopamine on ventrolateral thalamic inputs in cat motor cortex

Neuronal activity in several brain regions is modulated by dopaminergic inputs. When single neuronal activity/20 trials of single-pulse ventrolateral thalamic (VL) stimulation was extracellularly recorded in the in vivo, anesthetized cat motor cortex, iontophoretic application of dopamine (DA) elicited either suppression or, in a fewer instances, facilitation of evoked unitary responses. The predominant inhibition exerted by DA appeared to be consistent for successive trials, and a D 1, D 2, and D 1/D 2 receptor antagonist restored the effect, thereby reflecting a possible coexistence of two DA receptors. By contrast, only a fewer neurons’ response to DA displayed facilitation, which was not attenuated by DA antagonists. Moreover, subsequent trials with receptor agonist and antagonists induced inconsistent effects. Except for the jitters, single unit spikes showed invariant latency, which was constant during all recording parameters, and the mean latency remained unchanged. The modulatory effects mediated by DA did not reveal any substantial difference between short- and long-latency responses. Both pyramidal tract neurons and non-pyramidal tract neurons, determined on the basis of antidromic potentials from the pyramidal tract, responded to DA essentially in a similar manner. It appears that DA overall inhibits cat motor cortical neuronal activity in response to VL inputs. We propose that such DAergic inhibition of thalamocortical excitation in the motor cortex could be critical for ongoing sensorimotor transformation.

Local Application of Dopamine Inhibits Pyramidal Tract Neuron Activity in the Rodent Motor Cortex

Cortical neurons respond in a variety of ways to locally applied dopamine, perhaps because of the activation of different receptors within or among subpopulations of cells. This study was conducted to assess the effects of dopamine and the receptor subtypes that mediate the responses of a specific population of neurons, the pyramidal tract neurons (PTNs) in the rodent motor cortex. The specific subfamilies of dopamine receptors expressed by PTNs also were determined. PTNs were identified by antidromic stimulation in intact animals. Extracellular recordings of their spontaneous activity and glutamate-induced excitation were performed with multi-barrel pipettes to allow simultaneous recording and iontophoresis of several drugs. Prolonged (30 s) application of dopamine caused a progressive, nonlinear decrease in spontaneous firing rates for nearly all PTNs, with significant reductions from baseline spontaneous activity (71% of baseline levels) occurring between 20 and 30 s of iontophoresis. The D1 selective (SCH23390) and the D2 selective (eticlopride) antagonists were both effective in blocking dopamine-induced inhibition in nearly all PTNs. Mean firing levels were maintained within 3% of baseline levels during co-application of the D1 antagonist with dopamine and within 11% of baseline levels during co-application of the D2 antagonist and dopamine. SCH23390 was ineffective however, in 2 of 16 PTNs, and eticlopride was ineffective in 3 PTNs. The dopamine blockade by both antagonists in most neurons, along with the selective blockade by one, but not the other antagonist in a few neurons indicate that the overall population of PTNs exhibits a heterogeneous expression of dopamine receptors. The firing rate of PTNs was significantly enhanced by iontophoresis of glutamate (mean = 141% of baseline levels). These increases were attenuated significantly (mean= 98% of baseline) by co-application with dopamine in all PTNs, indicating dopaminergic interactions with glutamate transmission. The expression of dopamine receptors was studied with dual-labeling techniques. PTNs were identified by retrograde labeling with fast blue and the D1a, D2, or D5 receptor proteins were stained immunohistochemically. Some, but not all PTNs, showed labeling for D1a, D2, or D5 receptors. The D1a and D2 receptor immunoreactivity was observed primarily in the somata of PTNs, whereas D5 immunoreactivity extended well into the apical dendrites of PTNs. In accordance with findings of D1 and D2 receptor antagonism of dopamine's actions, the identification of three DA receptor subtypes on PTNs suggests that dopamine can directly modulate PTN activity through one or more receptor subtypes.

Focal clonus elicited by electrical stimulation of the motor cortex in humans

Focal clonic seizures are a frequent epileptic phenomenon. However, there are little data about their pathomechanism. In four patients with focal epilepsy and subdural electrodes, focal clonus was elicited by electrical stimulation of the motor cortex. Three additional patients underwent intraoperative stimulation of the spinal cord. Rhythmic clonic muscle responses were elicited by cortical stimulation with 20–50 Hz. The clonus consisted of simultaneous trains of compound muscle action potentials (CMAP) in agonistic and antagonistic muscles alternating with periods of muscular silence despite continuous stimulation. Clonus frequency decreased from 4.0–8.0 Hz at 50 Hz stimulation to 3.0–3.5 Hz at 20 Hz paralleled by a prolongation of the trains of CMAP. The stimulation frequency correlated with the number of stimuli blocked during relaxation. During the stable stimulation periods, the clonus frequency decreased over time. The number of stimuli which formed a train of CMAP and which were blocked during relaxation increased towards the end of the stimulation periods. Increasing intensity of stimulation at the same frequency converted a clonic to a tonic response. There was always an 1:1 relationship between stimulus and CMAP during spinal cord stimulation. We hypothesize that during cortical stimulation, clonus is elicited by synchronous activation of pyramidal tract (PT) neurons which results in excitation of intracortical GABA Bergic interneurons by recurrent axon-collaterals. This leads to stepwise hyperpolarization of PT neurons intermittently suppressing the output of PT neurons despite continuous stimulation. This mechanism can explain our finding that temporal and spatial summation of the stimuli were needed for clonus generation.

Abnormal distributions of callosal commissural and corticothalamic neurons in the cerebral neocortex of Shaking Rat Kawasaki

Shaking Rat Kawasaki ( SRK) is an autosomal recessive mutant rat recognized by unstable gait and tremor and by early death around the time of weaning. We previously reported that corticospinal tract neurons are malpositioned in the motor cortex of the SRK rat [Ikeda and Terashima (1997) J. Comp. Neurol. 383, 370–380]. In the present study, we examined the distribution pattern of callosal commissural (CC) and corticothalamic (CT) neurons of SRK and normal rats with the injection of horseradish peroxidase (HRP) into the contralateral hemisphere or wheat germ agglutinin-conjugated HRP into the ventral lateral thalamic nucleus. The intracortical distribution pattern of retrogradely labeled CC and CT neurons in the motor cortex of SRK rat was abnormal: CC neurons were more deeply situated and CT neurons were more superficially situated in the SRK cortex than the corresponding components in the normal cortex. Most of labeled CC and CT neurons had abnormal dendritic configurations. Statistical analysis revealed that the difference of the mean intracortical position of CC and CT neurons of the SRK was significantly different from the normal counterparts (Student’s t-test, P<0.01). Taken together with previous findings, our data demonstrate that the abnormal cytoarchitecture of SRK cortex resembles the reeler cortex.

Developmental Down-Regulation of GAP-43 Expression and Timing of Target Contact in Rat Corticospinal Neurons

During early nervous system development axons grow toward the target tissue that they will innervate. As axons invade target tissue, growth slows and ceases. Neurons express high levels of the growth-associated protein GAP-43 during developmental axon growth, declining with maturation. It has been suggested that target contact provides a signal which down-regulates GAP-43 expression. To study this issue in more detail, we used in situ hybridization to quantify relative changes in GAP-43 mRNA in corticospinal tract neurons identified by Fast Blue retrograde labeling. We also used anterograde transport of biotinylated dextran amine to study the invasion of target by corticospinal axons. We find that GAP-43 mRNA is high during the first postnatal week and then declines in two phases. Approximately half of the initial level of GAP-43 expression in corticospinal neurons is lost by P12; then expression remains at a plateau until P21. Between P21 and P28, GAP-43 expression again declines by half and then remains steady at the adult level (one fourth of initial level). Corticospinal axons initially invade spinal gray matter during the first 2 postnatal weeks, in a rostrocaudal gradient. Varicosities suggestive of terminal boutons become numerous during the third and fourth week, and the morphology of corticospinal axon terminals achieves the mature form at the end of the fourth week. These data suggest that the first phase of down-regulation of GAP-43 in corticospinal neurons is coincident with initial target contact and that the second phase is coincident with final maturation of terminal arborization.

Rhythm generation in monkey motor cortex explored using pyramidal tract stimulation.

We investigated whether stimulation of the pyramidal tract (PT) could reset the phase of 15-30 Hz beta oscillations observed in the macaque motor cortex. We recorded local field potentials (LFPs) and multiple single-unit activity from two conscious macaque monkeys performing a precision grip task. EMG activity was also recorded from the second animal. Single PT stimuli were delivered during the hold period of the task, when oscillations in the LFP were most prominent. Stimulus-triggered averaging of the LFP showed a phase-locked oscillatory response to PT stimulation. Frequency domain analysis revealed two components within the response: a 15-30 Hz component, which represented resetting of on-going beta rhythms, and a lower frequency 10 Hz response. Only the higher frequency could be observed in the EMG activity, at stronger stimulus intensities than were required for resetting the cortical rhythm. Stimulation of the PT during movement elicited a greatly reduced oscillatory response. Analysis of single-unit discharge confirmed that PT stimulation was capable of resetting periodic activity in motor cortex. The firing patterns of pyramidal tract neurones (PTNs) and unidentified neurones exhibited successive cycles of suppression and facilitation, time locked to the stimulus. We conclude that PTN activity directly influences the generation of the 15-30 Hz rhythm. These PTNs facilitate EMG activity in upper limb muscles, contributing to corticomuscular coherence at this same frequency. Since the earliest oscillatory effect observed following stimulation was a suppression of firing, we speculate that inhibitory feedback may be the key mechanism generating such oscillations in the motor cortex.

GABA-B-related activity in processing of transcallosal response in cat motor cortex.

GABA-ergic characteristics of transcallosal (TC) responses were studied with specific antagonists of both GABA-A and GABA-B receptor subtypes. We used a paired-pulse paradigm to get insight into the role of GABA in interhemispheric interactions between motor cortices. 3-Amino-2-(4-chlorophenyl)-propylphosphonic acid (phaclofen) and 3-aminopropyl-diethoxymethyl-phosphinic acid (CGP 35348) were used as GABA-B antagonists and bicuculline methiodide (BMI) was used to block the GABA-A receptor. Although both GABA-A and GABA-B antagonists increased spike discharge upon transcallosal stimulation, in both pyramidal tract and non-pyramidal tract neurons, they had different effects on the responses to the first and second stimuli of paired-pulse stimulation (200 msec interval). Although the inhibition seen with the second stimulus was greatly attenuated by antagonists of the GABA-B receptor, it was maintained in the presence of the GABA-A antagonist. These finding support a presynaptic regulation of callosal transmission by GABA-B receptors in the callosal synapse of the cat motor cortex.

The effects of prolonged intracortical microstimulation on the excitability of pyramidal tract neurons in the cat.

This study was conducted to examine the excitability changes induced in cerebral cortical neurons during prolonged microstimulation with a spatially dense microelectrodes array. The arrays of 16 iridium microelectrodes were implanted chronically into the postcruciate gyrus of cats. Neuronal responses characteristic of single pyramidal tract axons (ULRs) were recorded in the medullary pyramid. 7 h of pulsing of individual electrodes at 50 Hz and at 4 nC/ph induced little or no change in the ULRs' electrical thresholds. The thresholds also were quite stable when 4 of the 16 microelectrodes were pulsed on each of 14 consecutive days. However, when all 16 microelectrodes were pulsed for 7 h at 4 nC/ph, the threshold of approximately half of the ULRs became elevated. Recovery of excitability required 2-18 days. Prolonged sequential (interleaved) pulsing of the 16 microelectrodes induced less depression of excitability than did simultaneous pulsing, but only when the stimulus amplitude was low (12 A, 1.8 nC/ph). Stimulation at a higher amplitude (15 nC/ph) induced much more depression of excitability. These findings imply that multiple processes mediate the stimulation-induced depression of neuronal excitability. The data also demonstrate that the depression can be reduced by employing a stimulus regimen in which the inherent spatial resolution of the array is maximized (sequential pulsing at an amplitude in which there is minimal overlap of the effective current fields).

Cerebello-thalamic synapses and motor adaptation.

The cerebellum's influence on voluntary movement is mediated, in large part, through the cerebello-thalamo-cortical (CTC) pathway. Of particular relevance here are those neurons in the cerebellar nuclei that project, via thalamus, to pyramidal tract neurons in primary motor cortex. Several lines of evidence implicate cerebello-thalamic (CT) synaptic plasticity as a neural substrate underlying movement adaptation in adult animals. CT synapses exhibit a number of structural characteristics suggestive of a capacity for both formation of new synapses, and alterations in efficacy of transmission across existing synapses. Long-term potentiation can be evoked across CT synapses in vitro by high frequency stimulation, albeit in young animals. Evidence regarding the contribution of CT synaptic plasticity to two different types of movement adaptation in adult animals is conflicting. Adaptation involving a strengthening and re-coordination of voluntary movement is associated with an increase in density of CT synaptic boutons and an increase in number of synaptic vesicles available for immediate neurotransmitter release within each bouton. On the other hand, adaptation involving associative conditioning of a reduced sensorimotor neural circuit is associated with plasticity at thalamo-cortical but not CT synapses. These conflicting findings may reflect differences in the extent of synaptic re-organization that occurs at thalamic versus cortical levels, differences in the neural circuitry mediating each behavior, and/or differences in the spatio-temporal convergence of activity in the thalamus during the adaptive processes. It is concluded that CT synaptic plasticity can underlie movement adaptation if the adaptation requires reorganization of the cerebellum's influence on cerebral cortex.

Proliferation and Regeneration of Retrogradely Labeled Adult Rat Corticospinal Neurons in Culture

These are the first studies to demonstrate that adult rat corticospinal tract (CST) neurons, which were identified by retrograde neuronal labeling, retain regenerative and proliferative potential. To determine if adult CST neurons undergo cell division, we tested if these retrogradely labeled cells synthesize DNA by adding BrdU to the cultures 24 h prior to fixation of the cells. The result shows that adult corticospinal tract neurons are capable of DNA synthesis, and our total cell counts with labeled cells counts further suggest that these cells undergo cell division.

Motor cortex excitability in severe liver failure: effects of Molecular Adsorbent Recycling System

One patient, suffering from severe hepatic failure, who had not responded to the state of art therapy, was treated with the Molecular Adsorbent Recycling System (MARS). Recently the MARS has been introduced by Stange et al. as a new extracorporeal blood purification method. This system uses a double-sided albumin impregnated high-flux polysulphone filter and a closed-loop dialysate circuit, containing human serum albumin. The dialysate is continuously regenerated on-line by the perfusion over charcoal and adsorbent resin. The recent introduction of techniques, able to stimulate transcranially cerebral cortex, makes it possible to investigate non-invasively central motor circuits in man. We studied one patient (28 years old, female) with severe hepatic failure and a control population matched for age. After a preliminary standard central motor conduction study, we evaluated motor cortex excitability by measuring threshold for EMG responses recorded from right FDI. Comparison of results obtained before and after MARS makes it possible to study the effects of severe hepatic failure on intrinsic excitability properties of the motor cortex. Central motor conduction time was within normal limits in the patient. Patient threshold for responses was significantly higher than normal before MARS and dramatically decreased after the treatment. The decrease in resting motor threshold was concomitant to the improvement of her neurologic status and the decrease in total and conjugated bilirubin and bile acid observed after the procedure. Transcranial magnetic stimulation activates the pyramidal tract neurones transinaptically via excitatory interneurones. This is a first report that excitatory interneurones are reversibly involved during severe hepatic failure.