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PubMed2021

Comparative cellular analysis of motor cortex in human, marmoset and mouse.

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Animals↗
PubMed1979

Free amino acids in motor cortex of amyotrophic lateral sclerosis.

Free amino acids were estimated quantitatively in the motor cortex from 3 patients with amyotrophic lateral sclerosis (ALS) and 11 control subjects. Among 7 amino acids which showed statistically significant changes, taurine was the only one which was increased constantly and most markedly in the motor cortex of all the 3 ALS cases. It was suggested that the metabolism of sulfur amino acids might be affected in comparatively early stages of ALS.

Adult↗
PubMed1977

Columnar distribution of cortico-cortical fibers in the frontal association, limbic, and motor cortex of the developing rhesus monkey.

The terminal distribution of cortico-cortical connections was examined by autoradiography 7-8 days following injections of tritium labeled amino acids into the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex in monkeys ranging in age from 4 days to 5.5 months. Labeled axons originating in these various regions of the frontal lobe have topographically diverse ipsilateral and contralateral destinations but virtually all of these projections share a common mode of distribution: they terminate in distinct vertically oriented columns, 200-500 mum wide, that extend across all layers of cortex and alternate in regular sequence with columns of comparable width in which grains do not exceed background. Spatial periodicity in the pattern of transported label in such regions as the prefrontal association cortex, the retrosplenial limbic cortex and the motor cortex indicates that columination in the intracortical distribution of afferent fibers is not unique to sensory specific cortex but is instead a general feature of neocortical organization. A columnar mode of distribution of cortico-cortical projections is present in monkeys at all ages investigated but is especially well delineated in the youngest of them. Thus, grain concentrations within columns are very high in monkeys injected at 4 days of age, somewhat lower in monkeys injected at 39-45 days of age, and least dense in those injected at 5.5 months. The distinctness of the spatially segregated pattern of innervation in the cortex of neonates indicates that the columnar organization of association-fiber systems in the frontal and limbic cortex is achieved before or shortly after birth.

Animals↗
PubMed1979

Influences of cerebellar hemispherectomy on slow potentials in the motor cortex preceding self-paced hand movements in the monkey.

With chronically implanted electrodes, surface negative and deep positive, slowly increasing potentials were recorded in the forelimb area of the motor cortex prior to self-paced movements of the contralateral hand in monkeys. The slow premovement potentials were markedly reduced in size after ablation of the cerebellar hemisphere on the contralateral side to the motor cortex under recording. It was suggested that the cerebellar hemisphere (neocerebellum) participates in preparing the activity of the motor cortex prior to voluntary movements.

Animals↗
PubMedDate not supplied

[Participation of cat motor cortex neurons in the afferent reorganization of the "placing reaction"].

Neuronal activity of the cortical representation of the biceps (CRB) and triceps in the cat pericruciate motor cortex and EMG of the forepaw muscles were recorded during the performance of unconditioned (to a stimulation of the dorsal side of the paw) and conditioned (to ventral stimulation) placing reactions of the forepaw (PR). After learning: 1) ventral stimulation acquired the capacity to evoke (with a latency not exceeding 20 ms) the same enhancement of the CRB neuronal activity, as evoked by dorsal stimulation eliciting PR in naive animals; 2) EMG thresholds of biceps response to stimulation of the motor cortex through a microelectrode did not change: 3) likewise unchanged was the relative number and magnitude of CRB neuronal responses to a local tactile stimulation of the ventral side of the contralateral forepaw. The constanct sensory input to the motor cortex after learning apparently acquires the capacity to evoke an enhancement of CRB neuronal activity sufficient for achieving PR.

Animals↗
PubMed1977

Reversibility of lipofuscin accumulation caused by protein malnutrition in the motor cortex of squirrel monkeys, Saimiri scireus.

Lipofuscin pigment has been demonstrated histochemically in the motor cortex by the use of several histochemical and cytochemical methods in the healthy (maintained on a diet with 25% protein content) and protein malnourished (maintained on a diet with 2% protein content) adult animals. 4 animals in the latter category were rehabilitated over a period of 11 months and various histochemical techniques were repeated on the motor cortex of these animals. The healthy animals showed a somewhat uniform distribution of lipofuscin pigment in the neuronal perikarya with the perineuronal glia showing only slight occurrence of pigment bodies. The malnourished animals exhibited a significantly larger number of lipofuscin bodies in the neuronal as well as glial perikarya. The neurons, especially, showed aggregations of lipofuscin bodies characterized by a large increase in the activity of acid phosphatase and simple esterases. The rehabilitated animals, however, showed a decrease of lipofuscin pigment in the neuronal perikarya with a concomitant loss of lysosomal enzymes, while a significant increase of these bodies was observed in the perineuronal glial cells. It is evident that the formation of lipofuscin pigment gets accelerated under the extrinsic influence of dietary protein deprivation in the adult animals, but the process is reversed at least to some extent by halting the dietary deficiency or its correction by rehabilitation. The perineuronal glial cells appear to play a significant role in the removal of lipofuscin bodies from the neuronal perikarya. The significance of these observations has been discussed.

Animals↗
PubMed1977

[Transcallosal modulation of a focus of maximal activity in the motor cortex].

In acute experiments on cats, when recording EPs from 170 symmetrical points of the motor cortex, callosal influence on the maximal activity focus (MAF) was studied in conditions of stimulation of the sciatic nerves with different stimuli. After callosal transection, weak stimuli enlarged the MAF, strong one-narrowed it. The transcallosal modulation in intact brain is supposed to aid to delineate the MAF in the motor cortex and to exaggerate the differences between MAFs occurring at stimulation with different stimuli.

Animals↗
PubMed1979

The origin of the hind limb vasodilatation evoked by stimulation of the motor cortex in the cat.

In cats under Althesin anaesthesia, the hind limb area of the motor cortex has been stimulated by means of monopolar, semi-micro-electrodes with careful experimental control so as to avoid reflex effects evoked through stimulation of meningeal afferent fibres or stimulus spread to non-cortical structures. 2. Localized cortical stimulation which elicited muscle contractions in the contralateral hind limb also elicited vasodilation in the same limb: the stimulus threshold was the same for both effects, and the magnitude of the dilatation was related to the strength of contraction. 3. Reduction of the somatic motor response, caused by lesions in the medullary pyramidal tract, was accompanied by a parallel reduction of the vascular response. 4. Prevention of the motor response by gallamine or by spinal cord section at L4--L5 (which leaves the sympathetic outflow to the hind limbs intact) led to abolition of the vascular response. During recovery from gallamine, contraction and vasodilatation returned in parallel. 5. The muscle vasodilatation was insensitive to atropine or guanethidine. 6. It is concluded that the hind limb vasodilatation observed on stimulation of the motor cortex is simply a post-contraction hyperaemia, and that it is independent of the sympathic nervous system. Previous conclusions of a sympathetically mediated vasodilatation probably resulted from inadequate control of the stimulus or a failure to recognize weak muscle contractions.

Animals↗
PubMed1977

[Transformation of an afferent tactile signal into a motor command in the cat motor cortex].

The activity of 112 units of the cat precruciate motor cortex was studied simultaneously with the performance of a placing reaction of the foreleg to tactile stimulation of its distal parts. The response latency to the tactile stimulation of the foreleg was 30-40 ms for the electromyographic response of m. biceps brachii and 20 +/- 10 ms for the earliest-responses of the motor cortical neurons. The electrical reaction of m. biceps brachii occured 5-10 ms after the termination of the electrical stimulation of the cortex by a puls series (the series duration was 25 ms, the pulse duration 0.2 ms, frequency 400 per s). Two different types of excitatory reactions of the motor cortex units were found: the sensory (s) ones occured at each tactile stimulus and did not depend on the presence or absence of the foreleg motion; the motor (m) type of reactions developed simultaneously with the motor placing reaction of the foreleg only. The minimal latency of cortical m- and s-type discharge was 20 +/- 10 ms. Electrical stimulation (5-25 micronA) through the microelectrode placed in the locus of neuronal activity which increased during active flexion of the foreleg, provoked in 70% of cases the electrical response in m. biceps brachii.

Animals↗
PubMedDate not supplied

Neuron activity in rat hippocampus and motor cortex during discrimination reversal.

Chronic unit activity and gross movement were recorded from rats during two discrimination reversals in a classical appetitive conditioning situation. The anticipatory movement decreased in response to the former CS+ tone and increased to the previous CS- tone after each reversal. Hippocampus and motor cortex were differently related to these two kinds of behavioral change. Response rates of hippocampal neurons were more closely related to the increased movement response to the former CS- which now signaled food. Motor cortex neuron responses were more closely correlated with the decrease in movement responses to the former CS+ which became neutral after the reversal. It appeared that hippocampal neurons could have been involved in one cognitive aspect of the situation, motor cortex neurons in another. The data were related to current functional concepts of these brain regions.

Animals↗
PubMed1975

[Retrograde degeneration of the pyramidal cells in the motor cortex of apes (Macaca fascicularis)].

In three adult macaques the retrograde degeneration of cell bodies in the motor cortex was investigated 6 months after unilateral pyramidal tract section. Large and small Betz cells of the fifth layer were identified microscopically and counted. The analysis of the data reveals that after pyramidotomy, (1) contrary to our expectations from the extent of the pyramidal lesions, a surprising percentage of undegenerated Betz cells remains in the contralateral motor cortex, (2) a greater percentage of small rather than large cell survives, and (3) the greatest loss of cells is in the foot region, the smallest in the face region. The results are discussed in relation to the role of pyramidal axon collaterals in the survival of cell bodies, and the distinction between pyramidal cells and pyramidal tract cells.

Animals↗
PubMed1975

Recovery of motor function after lesions in motor cortex of monkey.

This behavioural study concerns the contribution of active retraining to motor recovery after a standard lesion in the motor cortex, and includes an evaluation of various retraining procedures. These problems have not previously been experimentally analysed in man or animal. Rhesus monkeys (27) were initially trained on two motor tasks which consisted of a pulling task, involving the proximal muscles of the upper limb, and a hand-grip task for the distal musculature. Strength of pulling and hand-grip were measured quantitatively. For brevity, only the hand grip data are described. After a plateau of proficient performance was achieved in both hands (usually 6-8 months), the cortical precentral forelimb area was surgically ablated on one side. Each animal was then randomly assigned to one of four experimental groups or to a sham operative control group. The groups differed with respect to the use of the contralateral and/or ipsilateral forelimb(s) in post-operative motor training on the same task. In addition, to evaluate the contribution of spontaneous post-operative recovery independent of retraining, we started to train two groups immediately after surgery; in the other two experimental groups the weak forelimb remained idle for the first four post-operative months. Combined training of the weak and normal limb, which resulted in 85% recovery in the weak limb, did not differ statistically from training the weak limb alone (79% recovery). This suggests that the critical factor in promoting recovery is training of the weak forelimb, presumably by 'activation' of the damaged hemisphere. The role of the ipsilateral (strong) limb appears negligible. When post-operative training in the weak limb was delayed four months, spontaneous recovery noted one week after the start of delayed training was about 50% compared with 9% recovery after one week in the groups retrained immediately after surgery (P less than 0.001). The 'immediate' groups, however, continued to improve over a six-month period to about 82% of their pre-operative performance. The 'delay' groups, by contrast, exhibited only slight further improvement, reaching a plateau of 67% recovery six months after the start of retraining (10 months post-operatively). This difference in recovery between the immediate and delay groups was significant at the 0.05 level. This confirms that active physical retraining facilitates motor recovery, although the mechanism remains obscure. The data also suggest that, to be most effective, the training should begin as soon as possible after the insult to the brain has occurred.

Animals↗
PubMed1979

Commissural columns in the sensory-motor cortex of monkeys.

Callosally projecting cells and the terminal ramifications of their axons were identified in the monkey sensory-motor cortex by retrograde and anterograde labeling techniques, often by double labeling cells and axons in the same animal. Bundles of callosal fibers terminate in small column-like zones 0.5-1 mm wide in the motor cortex (area 4) and in the first (SI) and second (SII) somatic sensory areas. Such columns are aligned in register to form elongated strips extending mediolaterally in the long axes of the pre- and postcentral gyri. Significant portions of area 4, SI and SII, in regions corresponding to the representations of the hand and foot, are not callosally connected. The cells of origin of callosal fibers in SI are largely confined to layer IIIB and form columns and strips corresponding to the above. In connected zones of SI, the callosal connection is reciprocal and precisely point-to point. This and the laminar distribution of the terminal ramifications of callosal fibers (to layers I-IV) suggest that callosal fibers may arise from the terminate upon exactly homotopic, column-like groups of layer IIIB pyramidal cells. Commissurally projecting cells and their terminal ramifications are not limited to particular architectonic fields or particular parts of fields in SI. All architectonic fields of SI project heterotopically to the contralateral SII.

Animals↗
PubMed1976

[Neuron activities of the motor cortex during conditioned eye blink reflex in rabbits (author's transl)].

Effects of the tone (CS) on neurons of the motor cortex were investigated in naive, pseudoconditioned, and conditioned rabbits. Conditioning to eye blink reflex was made by a combination of CS and air puff (US). Effects of electrical stimulation of the subcortical structures were also observed on the cortical neurons associated with the conditioned reflex. The results were as follows. (1) Proportion of neurons which significantly increased the firing rate in response to the CS, type E, was higher in the conditioned group than in other two groups. On the other hand, no group difference was found in the proportion of neurons which significantly decreased the firing rate to the stimulus, type I. (2) Most of the type E neurons in the conditioned rabbits began to fire at latencies of about 50 to 100 msec after the CS, preceding about 200 msec to the appearance of the peripheral conditioned responses (EMG). (3) Most of the type E neurons in the conditioned animals were more easily affected by stimulation of the medial geniculate body and the brain stem reticular formation. Based on the results mentioned above, it is concluded that in the rabbits conditioned to the eye blink reflex, excitability of neurons in the motor cortex is enhanced by the tone (CS), and by electrical stimulation to the medial geniculate body and the brain stem reticular formation.

Action Potentials↗
PubMed1976

[Morphological studies on interneuronal relations in the feline motor cortex].

Three types of neuronal joinings in the cat motor cortex are described. The joinings of the 1st type (nests, barrels) consist of some pyramidal cells, apical dendrites of which form the bundles. The consolidation of neurons is achieved by means of dendro-dentritic contacts, pyramidal neuron collaterals and the associative transcortical afferents. The joinings of the 2nd type (distant) are formed with the participation of intracortical connections between the pyramidal and stellate neurons and are placed as concentric formation. The joinings of the 3rd type are formed with the help of projection thalamo-cortical afferents and large horizontal collaterals of basket cells.

Animals↗
PubMed1979

[Bilateral motor cortex effects on interneurons of the ventral horn of the lumbar segments].

The ventral horn interneurons in the spinal cord L6-7 segments were recorded in anesthetized cats during stimulation of the pericruciate cortex of both cerebral hemispheres. The majority of ventral interneurons are activated by volleys from the contralateral motor cortex and nearly half of them--by volleys from the ipsilateral cortex as well. Two kinds of firing patterns occurred: separate spikes and bursts of spikes. The latency of the 1st type firing was significantly greater than that of the 2nd one. There was a close relation of convergence of the afferent and corticospinal volleys on ventral horn interneurons: neurons activated by ipsilateral afferents only received synaptic influence only from the contralateral motor cortex whereas neurons with ipsilateral as well as contralateral inputs were activated by corticospinal volleys from both hemispheres. The interneurons with bilateral segmental and supraspinal connections seem to be involved in integrative action as important elements of the neuronal mechanism of bilateral motor coordination.

Action Potentials↗
PubMed1976

[United neurons in the cat motor cortex].

Vertically oriented bundles of apical dendrites in the cat motor cortex are described by means of light and electron microscopy. Existence of desmoidal and dendro-dendritic contacts in the bundles is considered as the structural basis of neuronal electrotonic interaction within the limits of one column. Sliding axo-spinal contacts are described between the descending pyramidal axon in layer III and the pyramidal apical dentrite in layer V which, probably, serve for the purpose of regulating activity of the main cortical output elements.

Animals↗