Reactions of cat motor cortex neurons to stimulation of the pyramidal tract and ventroposterolateral thalamic nuclei

Responses of neurons of motor cortex evoked by stimulations of pyramidal tract (PT) and ventroposterolateral (VPL) nucleus of thalamus were studied in cats immobilized by Myorelaxin. Antidromic spikes were found in 22.6% and in 9.9% of cortical cells when PT and VPL were stimulated, respectively. Fast- and slow-conducting PT-neurones could be differentiated according to antidromic excitation latencies. PT stimulation evoked EPSPs in 46.3% of studied neurones and VPL stimulation--in 48.2% ones. Monosynaptic EPSPs were identified in responses of fast- and slow-conducting PT-units and of neurones projecting in VPL; mechanisms and functional role of such reactions are discussed. Di- and polysynaptic IPSPs were evoked in 74.5% of units by PT stimulation and in 94.4%--by VPL stimulation. Three groups of IPSPs were classified with durations to 120, 130-280 and more than 300 ms. Duration of PT-evoked IPSPs was higher in cortical neurones from surface layers and VPL-evoked ones--in units localized in deep layers.     

Cortical Overexpression of Neuronal Calcium Sensor-1 Induces Functional Plasticity in Spinal Cord Following Unilateral Pyramidal Tract Injury in Rat

Following trauma of the adult brain or spinal cord the injured axons of central neurons fail to regenerate or if intact display only limited anatomical plasticity through sprouting. Adult cortical neurons forming the corticospinal tract (CST) normally have low levels of the neuronal calcium sensor-1 (NCS1) protein. In primary cultured adult cortical neurons, the lentivector-induced overexpression of NCS1 induces neurite sprouting associated with increased phospho-Akt levels. When the PI3K/Akt signalling pathway was pharmacologically inhibited the NCS1-induced neurite sprouting was abolished. The overexpression of NCS1 in uninjured corticospinal neurons exhibited axonal sprouting across the midline into the CST-denervated side of the spinal cord following unilateral pyramidotomy. Improved forelimb function was demonstrated behaviourally and electrophysiologically. In injured corticospinal neurons, overexpression of NCS1 induced axonal sprouting and regeneration and also neuroprotection. These findings demonstrate that increasing the levels of intracellular NCS1 in injured and uninjured central neurons enhances their intrinsic anatomical plasticity within the injured adult central nervous system.     

Relation of slowly conducting pyramidal tract neurons to specific aspects of forearm movement.

PT neurons were recorded from monkeys performing a trained motor task that included tonic maintenance of a limb position, slow and controlled and then quick wrist movements. The results suggest that many of slowly conducting PTNs have preferential relations with specific aspects of slow or tonic motor acts.     

Effects of excitation of the central nuclei of the cerebellum on the activity of neurons in the pyramidal tract

The effect of excitation of the contralateral nuclei of the cerebellum on the activity of anti-dromically-identified fast and slow pyramidal neurons in the sensorimotor region (SMR) of the cerebral cortex was investigated in delicate experiments on unnarcotized cats immobilized with procurane. It was found that excitation of the above nuclei could evoke peak responses in the neurons of the pyramidal tract (PT), but more often it modified their background activity. These responses were more pronounced on excitation of the intermediate nucleus (IN) or the dentate nucleus (DN), although they also often arose on excitation of the fastigial nucleus (FN). Qualitatively different effects (stimulative and inhibitory) were observed in some neurons on excitation of different nuclei in the cerebellum. It was found that the nature of the responses by fast neurons in the PT to excitation of the central nuclei in the cerebellum did not differe substantially from the nature of the responses by slow neurons, but that the responses of the latter arose with a longer latent period, and in most cases were less pronounced.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 22–31, January–February, 1971.     

A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex

The effects of different orientations of a Cadwell round magnetic coil (MC) were compared with each other and with surface electrical stimulation of motor cortex in monkeys anesthetized with pentobarbital or urethane. Recordings were made from within the lateral corticospinal tract, either from axonal populations or with a microelectrode from individual axons. A lateral-sagittally orientated MC directly excited corticospinal neurons at lower stimulus intensity than was required for indirect, i.e., transsynaptic excitation via inputs to corticospinal neurons. By contrast, in 2 out of 3 macaques tested, a vertex-tangential orientation could excite corticospinal neurons indirectly at lower intensities than were required for direct excitation; at higher intensities, direct excitation also occurred.The site of direct corticospinal excitation by a lateral-sagitally oriented MC was inferred by comparing the response variability and latency to MC and surface electrical stimuli. Cathodal stimuli elicited more variable corticospinal population responses and later individual axonal responses than were obtained with anodal stimuli. The variability in response is attributed to interaction between nearby, on-going synaptic bombardment and the stimulus, implying that surface cathodal stimuli directly activate corticospinal neurons at the spike trigger zone (presumably the initial segment). By contrast, the consistency and reduced latency of the corticospinal responses to surface anodal stimuli are attributed to the direct excitation of corticospinal fibers within the white matter. When the stimulus intensity is clearly above threshold, surface anodal and cathodal stimuli can activate corticospinal neurons both directly and indirectly.Direct corticospinal excitation by the MC can resemble the effects of either surface anodal or surface cathodal stimuli. We conclude that the MC can activate corticospinal neurons at the spike trigger zone or their fibers deeper in white matter. The findings in the monkey are used to interpret the effects of different MC orientations in the human.     

小鼠大脑皮质脊髓投射神经元核糖体蛋白质相关基因表达的研究

该研究采用激光显微切割技术从小鼠大脑第五皮层捕获少量皮质脊髓投射神经元,并分析其分子生物学特征。首先,提取神经元微量RNA,再借助WT-ovation试剂盒扩增RNA,随后利用合成的cDNA进行荧光定量PCR实验,分析投射神经元核糖体蛋白相关基因的表达情况。结果发现,与大脑皮层其它皮层组织相比,第五皮层投射神经元内部分核糖体蛋白相关基因的表达相对较高。这表明第五皮层投射神经元可能具有活跃的蛋白质合成功能,是核糖体蛋白质的能量场所,借此维持第五皮层脊髓投射神经元长轴突和大胞体的能量需要。     

Corticospinal mirror neurons

Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons’ discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited ‘classical’ mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation (‘suppression mirror-neurons’). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.     

Distinct cortical migrations from the medial and lateral ganglionic eminences

Recent evidence suggests that projection neurons and interneurons of the cerebral cortex are generally derived from distinct proliferative zones. Cortical projection neurons originate from the cortical ventricular zone (VZ), and then migrate radially into the cortical mantle, whereas most cortical interneurons originate from the basal telencephalon and migrate tangentially into the developing cortex. Previous studies using methods that label both proliferative and postmitotic cells have found that cortical interneurons migrate from two major subdivisions of the developing basal telencephalon: the medial and lateral ganglionic eminences (MGE and LGE). Since these studies labeled cells by methods that do not distinguish between the proliferating cells and those that may have originated elsewhere, we have studied the contribution of the MGE and LGE to cortical interneurons using fate mapping and genetic methods. Transplantation of BrdU-labeled MGE or LGE neuroepithelium into the basal telencephalon of unlabeled telencephalic slices enabled us to follow the fate of neurons derived from each of these primordia. We have determined that early in neurogenesis GABA-expressing cells from the MGE tangentially migrate into the cerebral cortex, primarily via the intermediate zone, whereas cells from the LGE do not. Later in neurogenesis, LGE-derived cells also migrate into the cortex, although this migration occurs primarily through the subventricular zone. Some of these LGE-derived cells invade the cortical plate and express GABA, while others remain within the cortical proliferative zone and appear to become mitotically active late in gestation. In addition, by comparing the phenotypes of mouse mutants with differential effects on MGE and LGE migration, we provide evidence that the MGE and LGE may give rise to different subtypes of cortical interneurons.     

Corticospinal and Reticulospinal Contacts on Cervical Commissural and Long Descending Propriospinal Neurons in the Adult Rat Spinal Cord; Evidence for Powerful Reticulospinal Connections

Descending systems have a crucial role in the selection of motor output patterns by influencing the activity of interneuronal networks in the spinal cord. Commissural interneurons that project to the contralateral grey matter are key components of such networks as they coordinate left-right motor activity of fore and hind-limbs. The aim of this study was to determine if corticospinal (CST) and reticulospinal (RST) neurons make significant numbers of axonal contacts with cervical commissural interneurons. Two classes of commissural neurons were analysed: 1) local commissural interneurons (LCINs) in segments C4-5; 2) long descending propriospinal neurons (LDPNs) projecting from C4 to the rostral lumbar cord. Commissural interneurons were labelled with Fluorogold and CST and RST axons were labelled by injecting the b subunit of cholera toxin in the forelimb area of the primary somatosensory cortex or the medial longitudinal fasciculus respectively. The results show that LCINs and LDPNs receive few contacts from CST terminals but large numbers of contacts are formed by RST terminals. Use of vesicular glutamate and vesicular GABA transporters revealed that both types of cell received about 80% excitatory and 20% inhibitory RST contacts. Therefore the CST appears to have a minimal influence on LCINs and LDPNs but the RST has a powerful influence. This suggests that left-right activity in the rat spinal cord is not influenced directly via CST systems but is strongly controlled by the RST pathway. Many RST neurons have monosynaptic input from corticobulbar pathways therefore this pathway may provide an indirect route from the cortex to commissural systems. The cortico-reticulospinal-commissural system may also contribute to functional recovery following damage to the CST as it has the capacity to deliver information from the cortex to the spinal cord in the absence of direct CST input.     

Negative surface potential shift and responses of neurons and glial cells during tetanic stimulation of the cortical surface

The negative potential shift in response to tetanic stimulation of the surface of the cortex or thalamic nucleus was recorded from the cortical surface in cats lightly anesthetized with pentobarbital. Parallel intracellular recordings were obtained of activity of neurons and glial cells. Glial cells responded to this stimulation by slow depolarization, which, under certain conditions of stimulation, was followed by slow hyperpolarization; hyperpolarization shifts were observed in neurons. Depolarization and hyperpolarization of glial cells, like hyperpolarization of neurons, did not correlate in time with the development of a negative shift of the surface potential. It is postulated that this shift is a response of complex origin involving the participation not only of glial cells, but also of cortical neurons.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 14, No. 3, pp. 248–253, May–June, 1982.     

Corticotrigeminal motor pathway in the rat--I. Antidromic activation

1. The rat corticotrigeminal motor pathway was electrophysiologically investigated. 2. Fifty-one cortical neurons were antidromically activated by stimulation of the contralateral motor trigeminal nucleus (MTN). 3. Twenty-eight of the neurons were examined to see whether they were pyramidal tract (PT) neurons and seven were the PT neurons. 4. Forty peduncular axons were antidromically activated by stimulation of the contralateral MTN and eight of them were the PT axons. 5. Most MTN projecting axons showed slower conduction velocities than their stem anons.     

Identification of tuberculo-ventral neurons in the polymorphic layer of the rat dorsal cochlear nucleus

The tuberculo-ventral tract represents a short nervous circuit within the auditory cochlear nuclei. Tuberculo-ventral neurons of the dorsal cochlear nucleus send isofrequency inhibitory inputs to bushy cells of the ventral cochlear nucleus. Injection of wheat germ agglutinin conjugated to horseradish peroxidase into the rat ventral cochlear nucleus, labelled tuberculo-ventral neurons retrogradely in the deep polymorphic layer of the ipsilateral dorsal cochlear nucleus. Five to 20% of the perimeter of these cells was covered by synaptic boutons, most of which contained flat and pleomorphic vesicles. These boutons contained glycine and sometimes GABA. Occasional small axo-somatic boutons contained round vesicles and were immunonegative for both glycine and GABA. This study shows that the synaptic profile of tuberculo-ventral neurons is different from that of other medium-size glycinergic neurons within the polymorphic layer or more superficial regions of the dorsal cochlear nucleus like cartwheel neurons. In fact the latter mostly receive boutons that contain pleomorphic vesicles.     

Fezl is required for the birth and specification of corticospinal motor neurons

The molecular mechanisms controlling the differentiation of neural progenitors into distinct subtypes of neurons during neocortical development are unknown. Here, we report that Fezl is required for the specification of corticospinal motor neurons and other subcerebral projection neurons, which are absent from Fezl null mutant neocortex. There is neither an increase in cell death in Fezl(-/-) cortex nor abnormalities in migration, indicating that the absence of subcerebral projection neurons is due to a failure in fate specification. In striking contrast, other neuronal populations in the same and other cortical layers are born normally. Overexpression of Fezl results in excess production of subcerebral projection neurons and arrested migration of these neurons in the germinal zone. These data indicate that Fezl plays a central role in the specification of corticospinal motor neurons and other subcerebral projection neurons, controlling early decisions regarding lineage-specific differentiation from neural progenitors.     

刺激大鼠大脑脚影响脊髓伤害感受性传递的下行途径

在麻醉大鼠用部分切割脊髓的方法分析了刺激大脑脚影响脊髓背角伤害感受性神经元的下委途径。刺激ＣＰ对背角神经元伤害感受性反应（Ｃ－反应）的影响以抑制为,部分（３０．７％）神经元在抑制作用产生之前先被兴历,抑制作用主要是通过背索或背外侧索实现的,然而在多数神经元是两者共同作用的结果,其中ＤＬＦ的作用似乎更为重要。兴历作用则是通过ＤＦ实现的。由于大鼠的皮质脊髓束位于ＤＦ中,以上结果提示大脑皮层不仅可直接通     

Distribution of inhibitory synapses on the somata of pyramidal neurons in cat motor cortex

The mechanisms by which cortical neurons perform spatial and temporal integration of synaptic inputs are dependent, in large part, on the numbers, types, and distributions of their synapses. To further our understanding of these integrative mechanisms, we examined the distribution of synapses on identified classes of cortical neurons. Pyramidal cells in the cat motor cortex projecting either to the ipsilateral somatosensory cortex or to the spinal cord were labeled by the retrograde transport of horseradish peroxidase. Entire soma of selected corticocortical and corticospinal cells were examined using serial-section electron microscopy. The profiles of these somata and the synapses formed with each of these profiles were reconstructed from each thin section with a computer-aided morphometry system. All somatic synapses were of the symmetrical, presumably inhibitory type. For both cell types, these synapses were not homogeneously distributed over the somatic membrane, but were clustered at several discrete zones. The number and density of synapses on the somata of different corticocortical and corticospinal neurons were not significantly different. However, the density of these synapses was inversely correlated with the size of their postsynaptic somata. We discuss the significance of these findings to the integrative properties of cortical neurons.     

Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex

The mammalian cerebral cortex consists of six layers that are generated via coordinated neuronal migration during the embryonic period. Recent studies identified specific phases of radial migration of cortical neurons. After the final division, neurons transform from a multipolar to a bipolar shape within the subventricular zone-intermediate zone (SVZ-IZ) and then migrate along radial glial fibres. Mice lacking Cdk5 exhibit abnormal corticogenesis owing to neuronal migration defects. When we introduced GFP into migrating neurons at E14.5 by in utero electroporation, we observed migrating neurons in wild-type but not in Cdk5(-/-) embryos after 3-4 days. Introduction of the dominant-negative form of Cdk5 into the wild-type migrating neurons confirmed specific impairment of the multipolar-to-bipolar transition within the SVZ-IZ in a cell-autonomous manner. Cortex-specific Cdk5 conditional knockout mice showed inverted layering of the cerebral cortex and the layer V and callosal neurons, but not layer VI neurons, had severely impaired dendritic morphology. The amount of the dendritic protein Map2 was decreased in the cerebral cortex of Cdk5-deficient mice, and the axonal trajectory of cortical neurons within the cortex was also abnormal. These results indicate that Cdk5 is required for proper multipolar-to-bipolar transition, and a deficiency of Cdk5 results in abnormal morphology of pyramidal neurons. In addition, proper radial neuronal migration generates an inside-out pattern of cerebral cortex formation and normal axonal trajectories of cortical pyramidal neurons.     

Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses.

The adult central nervous system (CNS) of higher vertebrates displays a limited ability for self repair after traumatic injuries, leading to lasting functional deficits [1]. Small injuries can result in transient impairments, but the mechanisms of recovery are poorly understood [2]. At the cortical level, rearrangements of the sensory and motor representation maps often parallel recovery [3,4]. In the sensory system, studies have shown that cortical and subcortical mechanisms contribute to map rearrangements [5,6], but for the motor system the situation is less clear. Here we show that large-scale structural changes in the spared rostral part of the spinal cord occur simultaneously with shifts of a hind-limb motor cortex representation after traumatic spinal-cord injury. By intracortical microstimulation, we defined a cortical area that consistently and exclusively yielded hind-limb muscle responses in normal adult rats. Four weeks after a bilateral transsection of the corticospinal tract (CST) in the lower thoracic spinal cord, we again stimulated this cortical field and found forelimb, whisker, and trunk responses, thus demonstrating reorganization of the cortical motor representation. Anterograde tracing of corticospinal fibers originating from this former hind-limb area revealed that sprouting greatly increased the normally small number of collaterals that lead into the cervical spinal cord rostral to the lesion. We conclude that the corticospinal motor system has greater potential to adapt structurally to lesions than was previously believed and hypothesize that this spontaneous growth response is the basis for the observed motor representation rearrangements and contributes to functional recovery after incomplete lesions.     

Components of synaptic potentials of cat rubrospinal neurons evoked by corticofugal impulsation

EPSPs of rubrospinal neurons evoked by stimulation of the sensorimotor area of the cortex were studied in cats anesthetized with pentobarbital by means of intracellular recording. The involvement of corticospinal input in generating the EPSP was assessed by selective activation of corticospinal fibers at medullary pyramid level and by studying how they interact under the effects of cortical stimulation. It was shown that predominantly corticospinal and corticorubral neurons with slow-conducting axons are involved equally in the genesis of the first two components of complex EPSP. The cellular composition and mechanisms of corticofugal influences on red nucleus neurons are discussed.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 17, No. 5, pp. 692–700, September–October, 1985.