Layer-specific innervation of the dopamine-deficient frontal cortex in weaver mutant mice by grafted mesencephalic dopaminergic neurones

Summary The dopamine innervation of the frontal cortex originates in the A9 and A10 mesencephalic dopamine cell groups. In weaver mutant mice, there is a 77% frontocortical dopamine deficiency associated with losses of dopamine neurones in areas A9 and A10. The dopamine-depleted cortical areas of weaver mutant mice are receptive to reinnervation by afferent fibres originating in dopamine-containing mesencephalic grafts from normal donor embryos. In the anteromedial frontal lobe, reinnervation by tyrosine hydroxylase immunoreactive fibres is largely confined to the basal cortical layers whereas in the anterior cingulate cortex, tyrosine hydroxylase immunoreactive fibres also occupy superficial layers, including the molecular layer. Normally, the dopaminergic innervation of the anteromedial frontal lobe is distributed among the basal cortical layers (IV–VI), and the dopaminergic innervation of the cingulate cortex occupies both basal and superficial cortical layers. The pattern of innervation following transplantation indicates that, in repopulating dopamine-deficient cortical areas of recipient weaver mutants, graft-derived dopamine fibres show a preference for those layers which are normally invested by dopamine afferents.     

Chemical codes of sensory neurons innervating the guinea-pig adrenal gland

Retrograde neuronal tracing in combination with double-labelling immunofluorescence was applied to distinguish the chemical coding of guinea-pig primary sensory neurons projecting to the adrenal medulla and cortex. Seven subpopulations of retrogradely traced neurons were identified in thoracic spinal ganglia T1-L1. Five subpopulations contained immunolabelling either for calcitonin gene-related peptide (CGRP) alone (I), or for CGRP, together with substance (P (II), substance P/dynorphin (III), substance P/cholecystokinin (IV), and substance P/nitric oxide synthase (V), respectively. Two additional subpopulations of retrogradely traced neurons were distinct from these groups: neurofilament-immunoreactive neurons (VI), and cell bodies that were nonreactive to either of the antisera applied (VII). Nerve fibres in the adrenal medulla and cortex were equipped with the mediator combinations I, II, IV and VI. An additional meshwork of fibres solely labelled for nitric oxide synthase was visible in the medulla. Medullary as well as cortical fibres along endocrine tissue apparently lacked the chemical code V, while in the external cortex some fibres exhibited code III. Some intramedullary neuronal cell bodies revealed immunostaining for nitric oxide synthase, CGRP or substance P, providing an additional intrinsic adrenal innervation. Perikarya, immunolabelled for nitric oxide synthase, however, were too few to match with the large number of intramedullary nitric oxide synthase-immunoreactive fibres. A non-sensory participation is also supposed for the particularly dense intramedullary network of solely neurofilament-immunoreactive nerve fibres. The findings give evidence for a differential sensory innervation of the guineapig adrenal cortex and medulla. Specific sensory neuron subpopulations suggest that nervous control of adrenal functions is more complex than hitherto believed.     

Cortical Bundles in the Persistent, Photosynthetic Stems of Cacti

We examined 62 species in 45 genera of the cactus subfamilyCactoideae; all had collateral cortical bundles that permeatedthe broad, water-storing inner cortex and extended to the baseof the outer, photosynthetic palisade cortex. Mean distancebetween cortical bundles was 0.75 mm, similar to the mean spacing(0.74 mm) of veins in leaves of Pereskia, a genus of relictleaf-bearing cacti. In 16 species, both young and extremelyold stem cortex was available for study: in all of these, olderbundles had larger amounts of phloem than did younger bundles,indicating that phloem had been produced for many years. Inten species, older bundles also had more xylem than youngerbundles. In two genera (Rhipsalis and Selenicereus) there werecaps of primary phloem fibres, and in a single species (Pilosocereusmortensenii) cortical bundle xylem contained libriform fibres.All cortical bundle tracheary elements were narrow (radius range,0.91–8.2 µm; mode, 1.8–2.7 µm), similarto Pereskia leaf vein elements (radius range, 1.8–2.7µm); this was much narrower than stem wood vessels (radiusrange, 10–42 um; mode, 23–28 µm). Longitudinalconduction of water and nutrients probably occurs predominantlyin stem wood, with cortical bundles maintaining the broad, voluminouscortex, the outer part of which is the plant's photosynthetictissue and the inner part of which stores water and starch.The cortex of the Cactordeae contains numerous leaflike characters;homeotic genes may be involved in its morphogenesis. Cactaceae, cortical bundles, homeotic, xylem, phloem, evolution     

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.     

Cholinergic nerve fibres associated with the microvessels of the human cerebral cortex: a study based on monoclonal immunocytochemistry for choline acetyltrasferase

The distribution of cholinergic nerve fibres associated with the microvasculature of the human parietal cerebral cortex was investigated by immunocytochemistry, employing monoclonal antibodies against choline acetyl-transferase, the acetylcholine-synthesizing enzyme. The results revealed strongly immunoreactive nerve fibres in the tunica adventitia of arterioles penetrating the superficial cortical layers from the pial vasculature. Networks of stained nerve fibres were seen within the tunica muscularis of the radially directed arterioles that cross the intermediate and deep cortical laminae, and of their transverse and recurrent branches. Tiny positive nerve fibres were also seen around the cortex capillaries, some reaching the endothelial cells. The morphological data support the involvement of acetylcholine in microvasculature local regulation, possibly with a differentiated role in the arterioles and capillaries.     

Cytokeratin intermediate filament organisation and dynamics in the vegetal cortex of living Xenopus laevis oocytes and eggs

Cytokeratin intermediate filaments are prominent constituents of developing Xenopus oocytes and eggs, forming radial and cortical networks. In order to investigate the dynamics of the cortical cytokeratin network, we expressed EGFP-tagged Xenopus cytokeratin 1(8) in oocytes and eggs. The EGFP-cytokeratin co-assembled with endogenous partner cytokeratin proteins to form fluorescent filaments. Using time-lapse confocal microscopy, cytokeratin filament assembly was monitored in live Xenopus oocytes at different stages of oogenesis, and in the artificially-activated mature egg during the first cell cycle. In stage III to V oocytes, cytokeratin proteins formed a loose cortical geodesic network, which became more tightly bundled in stage VI oocytes. Maturation of oocytes into metaphase II-arrested eggs induced disassembly of the EGFP-cytokeratin network. Imaging live eggs after artificial activation allowed us to observe the reassembly of cytokeratin filaments in the vegetal cortex. The earliest observable structures were loose foci, which then extended into curly filament bundles. The position and orientation of these bundles altered with time, suggesting that forces were acting upon them. During cortical rotation, the cytokeratin network realigned into a parallel array that translocated in a directed manner at 5 microm/minute, relative to stationary cortex. The cytokeratin filaments are, therefore, moving in association with the bulk cytoplasm of the egg, suggesting that they may provide a structural role at the moving interface between cortex and cytoplasm.     

Distribution of neuropeptide Y immunoreactivity in human visual cortex and underlying white matter

Immunocytochemical techniques have been used to study neuropeptide Y (NPY) distribution in the human visual cortex (Brodman's areas 17, 18 and 19) NYP cell bodies belong mostly to inhibitory (multipolar and bitufted) but also to excitatory (bipolar and some pyramidal) neuronal types. Their distribution is similar in the three cortical areas studied: 20 to 40% of the NPY perikarya are located in the cortical gray matter, mostly in the deep layers, while the remaining 60 to 80% are located in the underlying white matter. Immunoreactive NPY processes form a rich network of intersecting fibers throughout the entire visual cortex. A superficial plexus (layers I and II) and a deep plexus (deep layer V and layer VI) of NPY fibers are present in areas 17, 18 and 19. In area 17, an additional well developed plexus is present in layers IVb and IVc. These plexuses receive branches from long parallel fibers arising from deep cortical layers or underlying white matter and terminating in superficial layers. Local or extrinsic NPY terminals wind around vessels in the cortex as well as in the white matter, and either penetrate them or form clusters of club endings on their walls. Our results suggest a role for NPY in human visual circuitry and in cortical blood flow regulation.     

Changes in the dendritic organization of the neurons of the isolated visual cortex of the cat]

The cortex of one hemisphere in cats was isolated according to M.M. Khananashwili method by means of surgical section of its projection fibres which connect it with subcortical structures. In five cats of means of Nissl's method the neuronal status of different cortical layers in the field 17 was studied during long postoperative terms (from 9 months up to 2 years). In 9 cats the neurons of the same field were impregnated after Golgi-Bubenett method and studied during the same postoperative terms. Cytological investigation in the majority of neurons did not reveal any pathologic changes during different postoperative terms up to one year. In two years, slight neuronal changes were noted presented in poor staining and vacuolization of cytoplasm. As a result of deafferentation performed shortening and thickness of dendritic branching was noted, as well as decrease in the number of thorns of large pyramids in layers III, IV, and V of the isolated cortex. Dendrites and thorns in small and medium-sized pyramids in layers II, III, IV, V, and VI were preserved to a great extent. It is possible to conclude, on the fact of thorns preserving in the major number of the neurons, that the neocortex possesses an enormous intracortical connective system that is responsible for the high degree of functional neuronal activity in the isolated cortex.     

Topical characteristics of the organization of the strio-cortical tract in the brain of the dog]

The study was carried out by the method of axo-terminal regeneration with impregnation of frontal sections of the brain with the Laidlaw liquid. It was shown that following a lesion of the dorsal and ventral area of the caudate nucleus in the dog's cerebral cortex correspondingly different amount of degenerating terminations of strio-cortical fibres could be revealed. These bonds were mainly directed into the VI and V layers of the cortex, namely into the frontal, precoronary, postcoronary, orbital and insular areas.     

Laminar distribution of benzodiazepine receptors in visual cortex of adult rat

The characteristics and distribution of benzodiazepine receptors in individual layers of the visual cortex of adult rats were examined with the 3H-flunitrazepam binding technique employed on intact tissue slices. The different visual cortical layers were separated by cutting serial cryocut sections horizontally to the cortical surface and collecting the slices from each individual cortical layer under anatomical control. Highest benzodiazepine receptor densities were found in layers IV and VI. A moderate receptor density was detected in layer V (80% of highest density). The lowest receptor binding was observed in cortical layers I and II/III, still representing 66% of the highest receptor density. Binding affinities varied slightly between layers with dissociation constants somewhat higher for layers IV to VI in comparison to layers I and II/III. The distinct laminar pattern of benzodiazepine receptors in rat visual cortex suggests a differential neuromodulatory significance of these receptors in each individual cortical layer.     

A formalisation of the neural assembly concept 1. Constraints on neural assembly size

Hebb proposed the concept of a neural assembly distributed across cortical tissue as a model for representation of information in the cerebral cortex. Later developments of the concept highlight the need for overlapping membership between independent assemblies, and the spread of activity throughout the assembly once it is activated above a critical level (ignition). Formalisation of the neural assembly concept, especially in relation to quantitative data from the real cortex, is at a very early stage. We consider two constraints on neural assembly size: (1) if a neural assembly is too small the fraction of its neurons that need to be active to ignite the whole assembly becomes unrealistically large; (2) if assemblies in a block of cortical tissue become too large then the block becomes ‘unsafe’, that is, unwanted spread from an active assembly to overlapping ones becomes inevitable. We consider variations in three parameters: neuronal firing threshold; connection density; and the total number of assemblies stored in the block of cortical tissue. Given biologically plausible values for these parameters we estimate maximum assembly size compatible with ignitability of individual assemblies, low probability of unwanted spread to overlapping assemblies, and safe operation of the block as a whole. Received: 7 March 1997 / Accepted in revised form: 1 July 1997     

The structure of the first auditory cortex (A I) in the cat. I.--Light microscopic observations on its organization

The cyto- and mieloarchitecture of the first auditory cortex (A I) was studied in the cat. The cortical layers II, III and IV are very densely populated by relatively uniform, round or stellate cells with 20 to 30 micro perikaryal diameter. The separation between these three layers, which is not possible in Nissl stained sections, becomes visible in 1 to 3 micro thick sections of plastic embedded material. nerve cells in layer II are randomly disposed, whilst they form in laver III loose rounded cellular groups, and in layer IV vertical cylinders which have 50 to 60 micro in outside diameter and a cell poor centre. These cylinders are best visible in 100 micro thick Nissl preparations, cut parallel to the pial surface. The cylinders may extend into layer V, which is comparatively cell poor. The VIth layer contains numerous round, stellate or fusiform cells with 20 to 30 micro in diameter. The IIIrd and Vth layers have few pyramidal perikarya which are small. Large or giant pyramidal cells are not found in A I. The overall thickness of the cortex in the convexity of A I is 2,000 micro, measured in sections of plastic blocks. The thickness of the 6 layers is 200 to 250 micro for layer I; 300 micro for layer II; 300 micro for layer III; 300 to 400, for layer IV; 350 micro for layer V; and 400 micro for layer VI. In preparations stained for myelin sheats A I is characterized by the presence of a very dense plexus of fibres running in all directions in the IVth, Vth anti VIth layers. These plexus obscurs the radiations of Meynert, giving a characteristic appearance to A I, since these radiations are prominent in the neighbouring cortical areas. In preliminary studies of Golgi rapid preparations of A I the cell types commonly present in others cortical areas were found. Pyramidal cells have small perikarya, and very long (600 micro) horizontal basal dendrites. Modified pyramidal cells (star pyramids) are the main cellular element in layer II and constitute one of the main sources of efferent fibres of A I. Several types of stellate cells were found, including a particular cell type, found very often in the IVth layer, with a very long horizontal axon. The specific thalamic afferents were identified as fibres with 5 or 8 micro in diameter, which run obliquely and sinuously through the VIth and Vth layers of A I. These fibres give off many branches with 1 to 2 micro in diameter, which pass to the IVth layer where they give off very thin sinuous branches, ending in small terminal knobs. The ramification of one of these fibres may spread horizontally over 800 micros, at the level of the IVth layer.     

Immunoreactive pancreatic polypeptide (PP) occurs in the central and peripheral nervous system: Preliminary immunocytochemical observations

Summary Pancreatic polypeptide (PP) is a candidate hormone of unknown physiological significance. It is produced by a population of endocrine cells in the pancreas. In the present study a PP-like peptide was found to occur in the mammalian and avian central and peripheral nervous systems. Immunoreactive nerve fibres and nerve cell bodies were widely distributed in the brain. Dense accumulations of nerve fibres occurred in the following areas: nucleus accumbens, interstitial nucleus of the stria terminalis, para- and periventricular hypothalamic nuclei, and medial preoptic area. In addition, nerve fibres were regularly seen in cortical areas. Immunoreactive perikarya were observed in the following regions: cortex, nucleus accumbens, neostriatum and septum. In the gut, immunoreactive nerve fibers were distributed in the myenteric plexus, in smooth muscle, around blood vessels, and in the core of the villi. Immunoreactive perikarya occurred in the submucosal and myenteric plexus, suggesting that PP immunoreactive nerves are intrinsic to the gut.In the species examined, the neuronal PP-like peptide could be demonstrated with an antiserum raised against avian PP, but not with those raised against bovine or human PP. Thus, neuronal PP is distinct from the PP that occurs in pancreatic endocrine cells.     

猫运动皮层神经元和S100、GFAP阳性细胞的年龄相关性变化

比较了青、老年猫运动皮层神经元与S100、GFAP免疫阳性胶质细胞的形态学变化,并探讨其与衰老过程中运动功能衰退的关系。采用Nissl染色显示青、老年猫运动皮层分层结构和神经元。免疫组织化学方法(SABC法)显示青、老年猫运动皮层S100免疫反应阳性(S100-immunoreactive,S100-IR)细胞及胶质纤维酸性蛋白免疫反应阳性(GFAP-immunoreactive,GFAP-IR)细胞。在Olympus显微镜下,用Moitcam5000数码成像与分析系统计数运动皮层各层神经元、S100-IR细胞及GFAP-IR细胞的数量,并随机抽样测量S100-IR、GFAP-IR细胞的胞体直径。与青年猫相比,老年猫运动皮层Ⅴ、Ⅵ层神经元密度显著下降(P<0.01),老年猫运动皮层中S100-IR和GFAP-IR细胞密度与胞体直径均显著增加(P<0.01),且细胞的免疫阳性反应较强。研究结果表明,猫运动皮层的神经元密度在衰老过程中Ⅴ、Ⅵ层神经元密度显著下降,有可能会降低老年个体运动皮层对运动的调控能力;随着衰老、运动皮层的星形胶质细胞出现明显的反应性活化与增生,这对维持大脑运动皮层神经元的活性和神经元之间的通讯联系,从而延缓老年性运动功能衰退具有重要意义。     

Formation of a system of exogenous tangential fibers in layer I of the cerebral cortex in the ontogeny of the dog]

During pre- and postnatal periods, development of nuclear projections of the diencephalon into the cortical layer I has been studied in dogs by means of silver nitrate impregnation after Cajal. It has been stated that after the 5th week of the intrauterine development a great number of fibres from the diencephalon, through the germ of the cortical lamina, begin penetrating into the layer 1 within the areas of the paleocortex, the island, the subicular field of the archicotex, the presubicular and entorhinal cortex. A little less fibres have been revealed in the sensomotor and temporoentorhinal areas on the convex surface of the frontal lobe and on the medial surface of the occipital lobe. At the places of their penetrating into the cortical layer 1, by the time of birth, the fibres have sprouted up thickness of the whole area of the hemisphere.     

Dynamics of axonal degeneration in the neuronally isolated cerebral cortex]

The brains of 11 cats were studied after unilateral isolation of the cortex after M. M. Khananashvily (1961) by means of resection of the projection fibres connecting the cortex with subcortical formations. The character and peculiarities of axonal degeneration in the large hemisphere cortex, were investigated after Nauta and Fink--Heimer. It was found that distribution of degenerating terminals in every layer depended on the time when the material was taken for investigation. Maximal concentration of the degenerating fibres was observed 3--5--10 days after the operation, then a gradual decrease in density of degeneration in every cortical layer was observed. By the 9th month after the operation, the processes of axonal degeneration completely came to their end. The problem of retrograde and anterograde nature of the axonal degeneration in the cortex of the large hemispheres was discussed in the article and it was demonstrated that in the field 4 of the neuronally isolated cortex it is of mixed nature.     

The effect of destroying the whisker follicles in mice on the sensory nerve, the thalamocortical radiation and cortical barrel development.

Electrolytic destruction of whisker follicles in mice on the day of birth has been found to cause degeneration in the sensory nerve fibres supplying the follicles. The severity of the degeneration has been assessed in animals between 2 and 20 days old by counting the total number of myelinated fibres in the maxillary nerves on both normal and lesioned sides. The degeneration is apparent after 2 days and by 20 days the nerve on the lesioned side contains only 38% of the normal fibre content. This degeneration has also been shown to involve the trigeminal root, central to the ganglion. In addition, the lesioning procedure modifies the terminations of thalamocortical fibres in the barrel region of the sensory cortex. These terminations are normally in clusters, each corresponding to a barrel, but, after lesioning the follicles, the terminals appear to be evenly distributed in layer IV and cortical barrel structures no longer develop. In postnatal mice, electrolytic destruction of whisker follicles had less effect upon maxillary nerve fibres and cortical barrels. The number of myelinated axons surviving until day 20 increased progressively with later lesioning to reach nearly 80% of the control level when lesions were made on day 10. Cortical barrels became secure earlier than the maxillary nerve, for a normal number of cortical barrels was present at day 12 when follicles were destroyed on day 4. The implications of these results for the formation of cortical barrels is discussed.     

Redundant mechanisms recruit actin into the contractile ring in silkworm spermatocytes

Cytokinesis is powered by the contraction of actomyosin filaments within the newly assembled contractile ring. Microtubules are a spindle component that is essential for the induction of cytokinesis. This induction could use central spindle and/or astral microtubules to stimulate cortical contraction around the spindle equator (equatorial stimulation). Alternatively, or in addition, induction could rely on astral microtubules to relax the polar cortex (polar relaxation). To investigate the relationship between microtubules, cortical stiffness, and contractile ring assembly, we used different configurations of microtubules to manipulate the distribution of actin in living silkworm spermatocytes. Mechanically repositioned, noninterdigitating microtubules can induce redistribution of actin at any region of the cortex by locally excluding cortical actin filaments. This cortical flow of actin promotes regional relaxation while increasing tension elsewhere (normally at the equatorial cortex). In contrast, repositioned interdigitating microtubule bundles use a novel mechanism to induce local stimulation of contractility anywhere within the cortex; at the antiparallel plus ends of central spindle microtubules, actin aggregates are rapidly assembled de novo and transported laterally to the equatorial cortex. Relaxation depends on microtubule dynamics but not on RhoA activity, whereas stimulation depends on RhoA activity but is largely independent of microtubule dynamics. We conclude that polar relaxation and equatorial stimulation mechanisms redundantly supply actin for contractile ring assembly, thus increasing the fidelity of cleavage.     

Global relationship between anatomical connectivity and activity propagation in the cerebral cortex

Anatomical connectivity is a prerequisite for cooperative interactions between cortical areas, but it has yet to be demonstrated that association fibre networks determine the macroscopical flow of activity in the cerebral cortex. To test this notion, we constructed a large-scale model of cortical areas whose interconnections were based on published anatomical data from tracing studies. Using this model we simulated the propagation of activity in response to activation of individual cortical areas and compared the resulting topographic activation patterns to electrophysiological observations on the global spread of epileptic activity following intracortical stimulation. Here we show that a neural network with connectivity derived from experimental data reproduces cortical propagation of activity significantly better than networks with different types of neighbourhood-based connectivity or random connections. Our results indicate that association fibres and their relative connection strengths are useful predictors of global topographic activation patterns in the cerebral cortex. This global structure-function relationship may open a door to explicit interpretation of cortical activation data in terms of underlying anatomical connectivity.