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Prolonged changes in synaptic efficiency and cellular excitability during learning.

A temporal analysis of changes in the response of the pyramidal tract using a model of prolonged potentiation revealed the substantial role of the mechanism of the heightening of total excitability of the cell at the initial stage of the formation of trace processes (an analog of the "dominant") which apparently promote the greater strengthening of the underlying mechanism of the CR, namely, the increase in the efficiency of synaptic associations. In the development of a CR in response to the stimulation of two points of the cortex, the increase in cell excitability was more marked in those experiments in which reinforcement was supplemented by the stimulation of the lateral hypothalamus, stimulation eliciting an alimentary reaction. These data make it possible to consider membrane plasticity as a cortical mechanism of the motivational component of reinforcement, a mechanism determining the dominant properties of the stage of generalization of the CR.

Animals↗

[Brain stem encephalitis in childhood].

OBJECTIVE: To present two cases of post-infectious encephalitis of the brain stem (ETC) in infancy, which is very infrequent at this age. CLINICAL CASES: Two patients aged 4 months and 9 months respectively had a previous history of a catarrhal illness a few days before the onset of encephalitis. The clinical condition was of subacute onset and torpid course, characterized by ataxia, reduced level of consciousness, involvement of the pyramidal tracts and paralysis of the cranial nerves. No significant information for the diagnosis of either case was obtained from CT. MR showed lesions at the level of the pons. However, the MR image did not correspond in seventy to the clinical condition. The clinical courses of the two patients were different. One case recovered with no sequelae. In the other case the cranial nerves and gait did not return to normal. CONCLUSIONS: In our experience, ETC is rarely seen in infancy. A high degree of suspicion and early treatment of ETC caused by the herpes simplex virus is necessary, since there is usually a high mortality or serious neurological sequelae.

Ataxia↗

Localization of central lesions by correlation of CT findings and neurological deficits.

In a prospective study involving 100 patients with lesions in the precentral gyrus or pyramidal tract we sought to correlate clinical findings and the results of an axial computed tomography (CT) to localize the lesion. In 85% of patients the size and location of the lesion visible on CT correlated well with the type and severity of the neurological symptoms and signs. However, in the remaining 15% of patients the CT findings did not correlate well with the patient's neurological deficit, showing that in these patients the anatomy of the central area was variable or distorted by the space-occupying lesion. We suggest that in such patients neurophysiological techniques be used intra-operatively for reliable localization of the motor strip.

Adolescent↗

[Dendritic action potentials of pyramidal neurons of the sensomotor cortex of the cerebral cortex of the cat].

The intracellular activity of pyramidal tract neurons during electrical stimulation of ventro-lateral and ventro-postero-lateral nuclei of thalamus was studied in acute experiments on cats immobilized by myorelaxants. Both somatic and presumably dendritic spikes (d-spikes) were observed. The latter were characterized by relatively low and variable (5-60 mV) amplitude; d-spikes occurred both spontaneously and in response to single shock and tetanic (8-14/s) stimulation of the thalamus. They were also induced by intracellular depolarizing current pulses and thalamic stimulation following iontophoretic application of strychnine. Simultaneously generated somatic and d-spikes revealed no collision between each other. Intracellular hyperpolarizing current pulses abolished only somatic spikes, while d-spikes were not affected. Dendritic origin with multiple generation zones of these variable spikes is suggested. Possible functional role of d-spike is discussed.

Action Potentials↗

Morphological cerebral asymmetries of modern man, fossil man, and nonhuman primate.

Cerebral asymmetries are common in modern and fossil man and the great apes. Those occurring most often are listed here: 1. The left sylvian fissure in man is longer than the right and in both fetal and adult brains the posterior end of the right sylvian fissure is commonly higher than the left. Associated with these findings, the left planum temporale is usually longer than the right. 2. The left occipital pole is often wider and usually protrudes more posteriorly than the right. 3. The left lateral ventricle, and especially the occipital horn, is usually larger than the right. 4. If one frontal pole extends beyond the other it is usually the right. 5. On X-ray computerized axial tomograms (CT) of the brain the right frontal lobe and the central portion of the right hemisphere more often measure wider than the left. 6. The CT studies commonly show a Yakovlevian anticlockwise torque (taking the nose as 12 o'clock), with the left occipital pole longer and often extending across the midline toward the right and a wider right hemisphere in its central and frontal portions and frequent forward protrusion of the right frontal pole. This is found also in newborns. 7. The posterior end of the sagittal sinus usually lies to the right of the midline and the sinus flows more directly into the right transverse sinus than into the left. 8. The right transverse sinus is usually higher than the left. 9. In left-handed and ambidextrous individuals the posterior ends of the sylvian fissures are more often nearly equal in height and the occipital regions are more often equal in width or the right may be wider. 10. The torque of the pyramidal tract and the hemispheral torque cannot at present be related to right- or left-handedness. Statistics concerning left-handedness are somewhat confounded, because it is likely that not a few individuals are left-handed because of an early injury of the left hemisphere in a normally right-handed individual. 11. Cerebral asymmetries are found in fossil man similar to those in modern man. 12. Asymmetries of the sylvian fissures similar to those of modern man have been found in the great apes and are particularly common in the orangutan. 13. The most striking and consistently present cerebral asymmetries found in adult and fetal brains are in the region of the posterior end of the sylvian fissures-- the areas generally regarded as a major importance in language function.

Adolescent↗

The effects of chronicity on burst structure in epileptogenic foci.

Pyramidal tract neurons (PTNs) from tungstic acid, cobalt and alumina gel foci in cat were studied for spontaneous and antidromically-evoked firing patterns. Specifically, the structured long-first-interval (LFI) burst was looked for. The LFI burst did occur spontaneously from PTNs in tungstic acid foci but could not be antidromically evoked. The LFI burst did not occur as often as would have bee predicted from cobalt and alumina foci, but, in foci older than 60 days, antidromically-evoked activity could be a burst which was structurally identical to those which occurred spontaneously. This data, in addition to that from acute penicillin foci, would indicate that the ability for single antidromic APs to evoke burst activity in PTNs is a function of the chronicity of the epileptic focus rather than the agent used to produce the focus.

Action Potentials↗

[Megalencephalic leucoencephalopathy with subcortical cysts: a study of a Lebanese family and a review of the literature].

INTRODUCTION: Megalencephalic leukoencephalopathy with subcortical cysts is a rare disease with autosomal recessive inheritance. MATERIALS AND METHODS: Two brothers born from a consanguineous marriage, presenting with the phenotype of the disease, their parents, brothers and sisters were examined. Magnetic resonance imaging of the brain was performed for the two patients. Sequence analysis of MLC1 (GenBank mRNA accession no. NM_OI5166) was performed for the patients using intronic primers. PCR restriction fragment length polymorphism analysis was done in patients, their parents and in 100 Lebanese controls in order to exclude gene polymorphism. RESULTS: The clinical features were characteristic of the disease, consisting of an early-onset macrocephaly followed by slowly progressive ataxia, pyramidal tract involvement and epileptic seizures. In one patient, the clinical manifestations were aggravated by a trivial brain trauma. In his brother and in one female cousin, a status epilepticus was precipitated by a febrile syndrome. The diffuse cerebral white matter lesions and the subcortical temporo-polar and frontal cysts, best seen on MRI, allowed making the diagnosis. Molecular genetics revealed a new mutation involving the MLC1 gene (263G-->T, exon 3). As a consequence, it affects the second transmembrane domain predict (G88V) of the MLC protein (protein sequence NP_055981). The mutation was confirmed by PCR restriction fragment length polymorphism analysis. CONCLUSION: Megalencephalic leucoencephalopathy with subcortical cysts may be individualized on clinical and radiological basis and confirmed by molecular genetics. In this Lebanese family, a new mutation of the MLC1 gene is reported.

Adolescent↗

Pharmacological analysis of conditioning in sensorimotor cortex neurons in a model.

In awake mobile rabbits, with electrodes implanted in the medial lemniscus, midbrain tegmental reticular nucleus, and pyramidal tract, combined stimulation of two brain of two brain structures resulted in elaboration of conditional connections in sensorimotor cortex neuronal populations. The main criterion of the conditioning was the appearance of changes in the neuronal activity on omission of the second stimulus. These changes represented a complex of electrical events, some of which were similar to and others different from the evoked responses to the second stimulus. Application of atropine, sulfate, chlorpromazine hydrochloride, serotonin creatinine sulfate, and gamma-aminobutyric acid (GABA) to the cortex at the site of the recording exerted a modulating effect on the conditional neuronal activity patterns. Of the above substances, GABA and atropine had the most pronounced effect. The GABA removed the short-latency components of the conditional changes which were similar to evoked responses. The atropine abolished the long-latency changes which differed from evoked responses.

Animals↗

Long-lasting potentiation of synaptic transmission requires postsynaptic modifications in the neocortex.

The mechanisms of associative long-lasting potentiation (LLP) of excitatory postsynaptic potentials (EPSPs) were studied in the motor cortex of anesthetized cats. Mono- and oligosynaptic EPSPs were evoked by stimulations of thalamic VL nucleus, pyramidal tract, callosal and somatosensory system and paired with orthodromic, antidromic or current-induced action potentials. EPSP-spike stimulus pairs with 0.1-0.2 Hz frequency and 0-200 ms interstimulus intervals induced increases in the amplitudes and durations of EPSPs for 40-60 min or longer after 20-50 pairings. The LLP was prevented when postsynaptic firing was blocked by intracellular current injection or by juxtasomatic application of gamma-aminobutyric acid. LLP was also prevented when the level of intracellular free calcium was lowered by the intracellular injection of the calcium chelator EGTA or when neuronal transport was blocked by the intracellular injection of colchicine. Neither EGTA nor colchicine blocked postsynaptic firing. Thus, these findings show that LLP in the neocortex is a postsynaptic phenomenon which requires conjunctive pre- and postsynaptic activity, adequate levels of intracellular free calcium, and functional intracellular transport.

Action Potentials↗

Antinociceptive effects of vaginal stimulation in rats: neurophysiological and behavioral studies.

The present studies extend previous findings that probing the vaginal cervix of rats blocks withdrawal reflexes and induces immobilization44. In the present studies, we report that this effect is apparently not due to an action on the final motor pathway, for limb or facial movement induced by electrical stimulation of the pyramidal tract was not suppressed by the probing. In contrast, the sensory response of neurons in the ventrobasal complex of the thalamus to noxious pinch stimulation was markedly attenuated by probing the vaginal cervix. However, the response of these neurons to gentle tactile stimulation was not attenuated, indicating a selective antinociceptive effect of the probing. The antinociceptive effect was not necessarily related to changes in arousal. These findings were supported by behavioral studies in which probing the vaginal cervix blocked vocalization in response to tail shock, and elevated the current threshold for eliciting vocalization in response to tail shock. Furthermore, during the probing, the rats were found to be capable of vocalizing in response to presumably non-noxious (lifting) stimulation, even though their vocalization response to noxious tail shock was suppresed. These studies suggest that probing the vaginal cervix rats exerts an analgesic action.

Animals↗

Activation of protein kinase C induces long-term changes of postsynaptic currents in neocortical neurons.

Intracellularly injected phorbol 12,13-dibutyrate (PdiB), a phorbol ester that activates protein kinase C (PKC), altered the postsynaptic responses of neurons of the motor cortex of cats. PdiB increased the amplitudes and durations of EPSPs and decreased the amplitudes and durations of IPSPs elicited by stimulation of the ventrolateral (VL) thalamus or the pyramidal tract (PT). The changes lasted for 50 min or longer. Corresponding changes in peak excitatory and inhibitory postsynaptic currents (EPSCs, IPSCs) were measured directly with the single electrode voltage clamp technique. Quantitative analysis of EPSCs in response to VL thalamic stimulation and IPSCs in response to PT stimulation made in a subgroup of fast PT cells suggested that PdiB acted within the injected neuron rather than presynaptically to alter the synaptic currents. No consistent changes in resting membrane parameters that would account for these modifications were found. Control injections of a phorbol ester that did not activate PKC failed to induce changes in synaptic responses or resting membrane properties. These observations suggest that activation of PKC, in vivo, can induce long-lasting changes in synaptic responses of neocortical neurons by direct modification of postsynaptic ion channel conductivities.

Animals↗

[Mechanism of the generation of evoked potentials in the rabbit neocortex].

This paper describes the analyses of evoked potentials recorded in different neocortical areas (Area precentralis 1 and 2, occipitalis 1 and 2) and elicited by different stimulation techniques (antidromic stimulation of the pyramidal tract, electrical stimulation of thalamic nuclei, the optic nerve and finally random dot stimulation of the retina). Field potentials were recorded intracortically with a 16-fold electrode. The analyses of field potentials with the current-source-density method yielded an estimation of the current source and sink density distributions within the six neocortical layers. Hence spatio-temporal patterns of layer specific activation processes (sinks and sources) can be described for the various evoked potentials. The results can be summarized as follows: every evoked potential shows a spatio-temporal pattern of sources and sinks which is independent of the neocortical area and the mode of stimulation. However, the late components of the evoked potentials show great variations in their generation mechanisms, thus indicating regional differences in neocortical architectonics. These observations are discussed with regard to morphology, electrical activity and functional properties of the studied neocortical areas.

Animals↗

Multiple sclerosis: assessment of lesional levels by means of transcranial stimulation.

Conduction in the Pyramidal Tracts (PTs) was studied in 30 healthy volunteers and 17 patients with definite Multiple Sclerosis. Central motor conduction time (CMCT) was assessed employing unipolar electrical transcranial stimulation and studies of the peripheral conduction time. Fourteen out of the seventeen studied patients showed CMCT abnormalities. No significative correlation was found between the intensity of muscle weakness and the slowness of conduction in the corresponding PTs. Subclinical abnormalities were detected in more than half of the studied patients. CMCT slowness showed a good correlation with the time course of the disease in the cortico-cervical (CCT) but not in the cortico-lumbar (CLT) tracts. Evidence favoring the existence of two different lesional levels along the PSs was found in 9 out of the 14 patients studied with recordings in the hand and leg muscles. Two patterns of abnormalities gave support to this conclusion. The first consisted of slowed conduction or inexcitability in both the CCT and CLT at one side, while only one of the contralateral PTs was impaired. In the second one, the 4 explored PTs showed a slowed conduction, but in addition, CMCT difference between the CLT and CCT was longer than normal. Both patterns suggest that one lesional level could be situated between the internal capsula and the lower cervical cord and the other in the spine below the 8th cervical methamera or in the corona radiata.

Adolescent↗

Neuronal plasticity and formation of new synaptic contacts follow pyramidal lesions and neutralization of Nogo-A: a light and electron microscopic study in the pontine nuclei of adult rats.

Regeneration and compensatory sprouting are limited after lesions in the mature mammalian central nervous system in contrast to the developing central nervous system (CNS). After neutralization of the growth inhibitor Nogo-A, however, massive sprouting and rearrangements of fiber connections occurred after unilateral pyramidal tract lesions in adult rats: Corticofugal fibers from the lesioned side crossed the midline of the brainstem and innervated the contralateral basilar pontine nuclei. To determine whether these newly sprouted fibers formed synaptic contacts, we analyzed the corticofugal fibers in the basilar pontine nuclei contralateral to the lesion by light and electron microscopy 2 weeks after pyramidotomy and treatment with the Nogo-A-inhibiting monoclonal antibody IN-1 (mAb IN-1). The mAb IN-1, but not a control antibody, led to structural changes in the basilar pons ipsilateral and contralateral to the lesion site. Fibers sprouted across the pontine midline and terminated topographically. They established asymmetric synaptic contacts with the characteristics of normal corticopontine terminals. These results show that adult CNS fibers are able to sprout and to form new synaptic contacts after a lesion when a growth-permissive microenvironment is provided.

Animals↗

Activity of the motor cortex during scratching.

In awake cats sitting with the head restrained, scratching was evoked using stimulation of the ear. Cats scratched the shoulder area, consistently failing to reach the ear. Kinematics of the hind limb movements and the activity of ankle muscles, however, were similar to those reported earlier in unrestrained cats. The activity of single neurons in the hind limb representation of the motor cortex, including pyramidal tract neurons (PTNs), was examined. During the protraction stage of the scratch response, the activity in 35% of the neurons increased and in 50% decreased compared with rest. During the rhythmic stage, the motor cortex population activity was approximately two times higher compared with rest, because the activity of 53% of neurons increased and that of 33% decreased in this stage. The activity of 61% of neurons was modulated in the scratching rhythm. The average depth of frequency modulation was 12.1 +/- 5.3%, similar to that reported earlier for locomotion. The phases of activity of different neurons were approximately evenly distributed over the scratch cycle. There was no simple correlation between resting receptive field properties and the activity of neurons during the scratch response. We conclude that the motor cortex participates in both the protraction and the rhythmic stages of the scratch response.

Animals↗

Diffusion tensor imaging detects corticospinal tract involvement at multiple levels in amyotrophic lateral sclerosis.

BACKGROUND: Histopathological studies of amyotrophic lateral sclerosis (ALS) are of end stage disease. Diffusion tensor imaging (DTI) provides the opportunity to investigate indirectly corticospinal tract pathology of ALS in vivo. METHODS: DTI was used to study the water diffusion characteristics of the corticospinal tracts in 21 patients with ALS and 14 normal controls. The authors measured the fractional anisotropy (FA) and mean diffusivity (MD) along the pyramidal tracts from the internal capsules down to the pyramids. A mixed model regression analysis was used to compare FA and MD between the ALS and control groups. RESULTS: FA showed a downward linear trend from the cerebral peduncles to the pyramids and was lower in the ALS group than controls at multiple levels of the corticospinal tract. At the internal capsules, FA was higher on the right. MD showed an upward trend, progressing caudally from the internal capsules to the pyramids. MD was higher at the level of the internal capsule in the ALS group, but caudally this difference was not maintained. No correlations were found between clinical markers of disability and water diffusion indices. CONCLUSIONS: These findings provide insights into the pathological processes of ALS. Differences in diffusion characteristics at different anatomical levels may relate to underlying tract architecture or the distribution of pathological damage in ALS. Further development may permit monitoring of progression and treatment of disease.

Adult↗

Sources of input to interneurones mediating group I non-reciprocal inhibition of motoneurones in the cat.

Intracellular recordings have been made from laminae V-VI interneurones interposed in pathways of non-reciprocal inhibition of motoneurones from group I afferents of triceps surae and/or plantaris. A comparison of actions of brief stretches of triceps surae and plantaris with actions of electrical stimulation of nerves of these muscles revealed that I a afferents influenced about a half of the interneurones excited by I b afferents. Electrical stimulation of seven muscles nerves, three cutaneous nerves, posterior knee joint and interosseous nerves, the red nucleus and the pyramidal tract, evoked excitatory post-synaptic potentials (e.p.s.p.s) in various proportions of interneurones. Most of the interneurones were excited monosynaptically, or both monosynaptically and disynaptically by group I afferents. This, together with a very small proportion of interneurones in which e.p.s.p.s were evoked only disynaptically, indicates that the same last-order interneurones may subserve di- and trisynaptically evoked inhibition of motoneurones. Other fibre systems excited these interneurones monosynaptically (interosseal, rubro- and corticospinal), disynaptically (cutaneous, rubro- and corticospinal) and polysynaptically. The coupling of the earliest e.p.s.p.s from group II and joint afferents could not be established, but was consistent with their mediation by only one or two interposed interneurones. Inhibition was evoked from all fibre systems with excitatory input to the same or to other interneurones of the sample, except from group II afferents, the effects of which were found in a much smaller number of cells and may not be fully representative.

Action Potentials↗

Evoked potentials in multiple system atrophy (MSA).

OBJECTIVES: To study the involvement of pyramidal tracts and sensory pathways in multiple system atrophy (MSA). MATERIALS AND METHODS: Evoked potential studies were performed in 45 MSA patients suffering from either MSA of cerebellar type (MSA-C) or MSA of parkinsonian type (MSA-P). RESULTS: Motor evoked potentials were normal in all MSA patients, whereas visual and somatosensory evoked potential abnormalities were found in about 40% of the MSA patients with no significant difference between the cerebellar (MSA-C) and parkinsonian (MSA-P) subgroup. Abnormal latencies of wave III in brainstem auditory evoked potentials were significantly more frequent in MSA-C. CONCLUSIONS: Abnormalities of somatosensory, visual and auditory evoked potentials are frequent findings in MSA, whereas abnormal motor evoked potentials are not a characteristic feature of the disease.

Adult↗