Networks of neural nuclei

A new model of a neural system is presented. Neurons are considered to operate as parts of a neuronal ensemble called a neural nucleus, which has a homogeneous structure in connections among neurons. An excitatory nucleus shows one of the three fundamental properties in terms of the time course of the number of firing neurons in it: (i) increasing, (ii) constantly sustained and (iii) decreasing excitation. Mutually interacting structures of the neural nuclei are called nuclear networks. Simple nuclear networks consisting of one or a few nuclei are described to have functions such as integration, normalization and oscillation. In the nuclear networks inhibitory nuclei play an important role from the functional standpoint.     

Tubulin isotypes and their interaction with microtubule associated proteins

Summary To assay the functional significance of the multiple but closely related - and -tubulin polypeptides (termed isotypes) that are expressed in mammalian cells, we have generated a number of sera that uniquely discriminate among these isotypes. These sera have been used to demonstrate that there is no subcellular sorting of either - or -tubulin isotypes among microtubules of diverse function, either in cells growing in culture or in tissues consisting of cell types that contain specialized kinds of microtubule. In spite of this failure to segregate between functionally distinct kinds of microtubule, the fact that isotype-specific amino acid sequences have been strictly conserved over extensive periods of evolutionary time argues persuasively for a functional role for the different tubulin gene products. One possibility is that they are required for specific interactions with microtubule associated proteins (MAPs), and that tubulin isotypes have coevolved with different cell type-specific MAPs with which they must interact. We have tested this hypothesis by examining the distribution of -tubulin isotypes in mammalian cerebellum in relationship to the known patterns of expression of a number of MAPs, and find that these patterns correlate in the case of M 2 and MAP 3, and M 6 and MAP 1 a. These data, plus emerging data based on a structural analysis of tau, MAP 1 b and MAP 2 obtained via sequence determination of cloned cDNAs, are discussed in terms of the possible functional significance of tubulin isotype/MAP interactionsin vivo.     

Developmental aspects of the innervation of skeletal muscle fibers in the chick embryo

Summary The M. complexus in the chick, commonly called the hatching muscle, undergoes conspicuous growth during the latter stages of embryonic development. Myogenesis of this muscle was compared to that of M. biceps femoris with regard to development of types of muscle fiber and their innervation. In both muscles fibers are of relatively uniform size and show little growth in diameter between 12 days of development and hatching; fibers develop continuously and display a wide range of diameters at all stages.Initial thickenings on the sarcolemma of fibers where axons are closely approximate were first observed at 10 days of development in both muscles. In both muscles fibers are innervated prior to fibers. Terminal axon networks bridge intercellular spaces and contact fibers in different myogenic clusters, fibers that develop on the surface membrane of fibers exhibit focal thickenings of the membrane and some cell projections that are directed toward axon- fiber contacts. These changes occurred only in fibers of M. complexus.At 14 days of embryogenesis, the processes of synaptogenesis and of myelin formation are less advanced in M. biceps femoris than in M. complexus. At this stage a fibers were observed to be innervated in M. complexus, but not yet in M. biceps femoris. Each fiber was observed to be encircled by several preterminal axons.It is concluded that the earlier development of M. complexus is correlated with an equally early development of nerve-muscle interactions.This work was supported in part by a grant from the Muscular Dystrophy Association of America, Inc.Postdoctoral Fellow of the Muscular Dystrophy Association I would like to thank Professor Dr. H. Tamate for his valuable advise. I am also grateful to Dr. L. Doerr, H. Stokes and Judi K. Lund for their advice and skilled technical assistance     

Somatic embryogenesis and plant regeneration in wild cotton (Gossypium klotzschianum)

A simple and efficient method for high frequency somatic embryogenesis and plant regeneration from hypocotyl-derived cultures and suspension cultures of Gossypium klotzschianum Anderss, a wild, diploid species of cotton is described here. Embryogenic cultures were induced from hypocotyl sections on MSB medium with 0.9 M 2,4-D and 2.32 M kinetin. MSB medium containing 0.045 M 2,4-D, 0.93 M kinetin, 2.46 M IBA promoted embryogenic culture proliferation and embryo development. Suspension cultures with 0.23 M 2,4-D and 0.93 M kinetin also produced many embryos. Somatic embryos cultured on MSB medium with PGRs produced secondary embryos, and embryos developed into normal plantlets on PGR-free MSB medium. Regenerated plantlets were transferred onto the quarter-strength MSB medium with 0.5% active charcoal to avoid recallusing. Hypocotyls were better than cotyledons for culture induction and plant regeneration. 2,4-D and kinetin were essential for culture induction and maintenance.     

Die Gro?gefieder-Mauser des Steinkauzes(Athene noctua)

Zusammenfassung Zwei im Jahre 1959 geschlüpfte Steinkäuze (Athene noctua) dienten zur Untersuchung des zeitlichen Verlaufs ihrer ersten, 1960 einsetzenden Großgefieder-Mauser.98 Tage () bzw. 99 Tage () nach der ersten Schwungfeder fiel die letzte Schwungfeder aus. Die Flügelmauser setzte beim am 13. Juni, beim am 8. Juni ein. Ihr Verlauf geht aus den Diagrammen 1 und 2 hervor.Die 12 Armschwingen wurden wie beiStrix aluco von drei Foci aus erneuert, nämlich von A 12 bis A 8 descendent, von A 1 bis A 4 ascendent und von A 5 bis A 7 gleichfalls ascendent. — Die vier Federn des Daumenfittichs fielen in descendenter Reihenfolge, die 6 Steuerfeder-Paare beim nahezu synchron (binnen 4 Tagen), etwa zugleich mit dem Ausfall von H 3.

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Summary The sequence and chronology of the first moult of flight-feathers has been studied in two captive specimens of the Little Owl,Athene noctua. The result is shown in the diagrams 1 and 2. InStrix aluco, the sequence (diagr. 3) agrees in principle with that followed byAthene noctua.

     

A human SP-C promoter fragment targets α1-proteinase inhibitor gene expression to lung alveolar type II cells in transgenic mice

A 1.277 kb promoter fragment of the gene encoding one of the lung surfactant proteins, SP-C, was cloned from a human genomic library and characterized using the human 1-proteinase inhibitor (1PI) gene as reporter. Messenger RNA for human 1PI isolated from a single transgenic mouse line was detected solely in lung tissue. Using immunogold electron microscopy, accumulation of human 1PI was shown unambiguously to occur only in type II pulmonary cells and, in discrete amounts, in the alveolar lining fluid. The protein was secreted and glycosylated showing a molecular weight close to that of plasma-derived human 1PI.     

Epilepsy and weather: A significant correlation between the onset of epileptic seizures and specific atmospherics — a pilot study

The possibility of connections between weather and the onset of epileptic seizures has long been suggested (see, for example, the Hammurabi Codex 1600 BC). Work in the 20th Century points to a probability that the onset of both local and generalised epilepsy is significantly influenced by an interaction between genetic and extrinsic factors. In an attempt to clarify the situation a detailed study of the history of 315 attacks from 1 Jan. to 31 July 1981 suffered by a small number of patients in Munich has been undertaken. Although linkages between classical meteorological parameters and the onset of seizures are very weak, links with more generalised indexes (e.g. passage of fronts and disturbances) are more promising. However, the correlation between onsets and atmospherics of 28 KHz (positive) and 10 KHz (negative) impulses, are significant and call for urgent study.     

Distribution of CGRP-, VIP-, DβH-, SP-, and NPY-immunoreactive nerves in the periosteum of the rat

Summary In light of the possible role peripheral nerves may play in bone metabolism, the morphology of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal peptide (VIP)-, substance P (SP)-, neuropeptide Y (NPY)-, and dopamine--hydroxylase (DH)-immunoreactive nerve fibers was examined in whole-mount preparations of periosteum of membranous bones (calvaria, mandible) and long bones (tibia) from the rat. Periosteum from animals treated to remove selectively either the sympathetic or fine-caliber primary afferent nerves was also examined to determine the origin of the nerve fibers. We found a consistent and often dense innervation of the periosteum. The innervation patterns of the calvaria and mandible were similar, with networks of nerves spread across the surface of the bone. Nerves in the tibial periosteum were oriented in the longitudinal axis and were more numerous at the epiphyses than in the mid-shaft region. CGRP-immunoreactive fibers were widely and densely distributed. The presence of populations of CGRP-immunoreactive fibers of differing calibers and perivascular arrangements suggests that such nerves in bone tissues may serve different functions. SP-immunoreactivity was present in a fine network of varicose fibers in the superficial layers of the periosteum. CGRP- and SP-immunoreactive nerve fibers were dramatically reduced in periosteum of capsaicin-treated animals as compared to controls, indicating the sensory origin of these nerves. VIP-immunoreactive nerve fibers were distributed in the periosteum of mandible and calvaria as small networks and individual fine varicose fibers. In tibial periosteum, larger networks of these fibers were visible. VIP-immunoreactive nerve fibers in the periosteum were associated with both vascular and nonvascular elements within the layers of cells closest to the bone, suggesting that VIP may serve more than one function in periosteal tissues. NPY-immunoreactive fibers were largely confined to vascular elements; occasional fibers were observed among the bone-lining cells. DH-immunoreactivity was associated only with blood vessels. VIP-, NPY-, and DH-immunoreactivities were dramatically reduced in the periosteum of guanethidinetreated animals, indicating the sympathetic origin of these nerves.     

Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RIα subunit: p53-independent mechanism of action

The enhanced expression of the RI subunit of cyclic AMP-dependent protein kinase type 1 (PKA-I) has been correlated with cancer cell growth. We have investigated the effects of sequence-specific inhibition of RI gene expression on the growth of MCF-7 human breast cancer cells. We report that RI antisense treatment results in a reduction in RI expression at both mRNA and protein levels and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology, cleavage of poly(ADP-ribose) polymerase (PARP) and appearance of apoptotic nuclei. In addition, bcl-2 protein level was reduced and p53 expression increased in growth arrested cells. Interestingly, RI antisense inhibited cell viability and induced apoptosis in the absence of p53, suggesting that these actions of RI antisense are exerted independent of p53. In contrast, two- and four-base mismatched control oligonucleotides had no effect on either cell growth or morphology. These results demonstrate that the RI antisense, which efficiently depletes the growth stimulatory molecule RI, induces cell differentiation and apoptosis, providing a new approach to combat breast cancer cell growth.     

Correlation of the characteristics of evoked EEG potentials with individual peculiarities of attention in children

We studied correlations of the main parameters of evoked EEG potentials (EP) with individual characteristics of attention in children and teenagers. One hundred and one healthy children (dextrals) took part in the tests. Among them, 26 and 30 children were 5 to 7 and 10 to 12 years old, while the third age group included 45 teenagers (15 to 16 years old). We recorded EP and measured the time of a sensorimotor reaction in the following experimental paradigm. Its program provided automated presentation of a pair of acoustic signals, preliminary and imperative; the subject had to perform a motor reaction, pushing a button with the right thumb, with a minimum delay after the second stimulus. Visual feedback signals informed the subject about the successful or inadequate performance of the reaction (time of reaction was shorter than or exceeded a limit value). Indices characterizing the level of attention were estimated using Find and delete and Schultes tables techniques. A well-manifested N2 component of the EP related to the preliminary signal was a specific feature in the group of 5- to 7-year-old children, while the contingent negative variation (CNV) preceding the motor reaction was poorly developed in this group. The best characteristics of attention in these and older (10 to 12 years old) children were typical of subjects with maximally expressed N1-P2 waves. In teenagers, the best attention was typical of subjects with the highest-amplitude P1 and P2 components, CNV, and P300 wave and with the lowest amplitude of the N1 component.Neirofiziologiya/Neurophysiology, Vol. 36, No. 4, pp. 313–321, July–August, 2004.This revised version was published online in April 2005 with a corrected cover date.     

The connectivity of cones and cone horizontal cells in a mosaic-type teleost retina

Summary A total of 20 Golgi-impregnated cone horizontal cells of Nannacara anomala (Cichlidae) were studied in alternating semi- and ultrathin sections in order to examine their connections with the overlying square mosaic of equal double and central single cones. Cone horizontal cells exhibit three types of processes: (a) the long horizontal axon, (b) short horizontal dendrites with a terminal swelling, and (c) cone contacting processes ascending towards the outer plexiform layer. As seen in tangential sections, the latter processes are arranged in the form of two concentric circles including a central spot. The processes of the inner circle contact the eight double cone pedicles of one square unit: processes of the outer circle contact eight more double cone pedicles which are directly adjacent to the square unit. The central spot represents a process which contacts the central single cone. Processes of the inner circle most often terminate in a dichotomous branching which represents the lateral elements to one ribbon synapse, whereas in the outer circle only a single terminal swelling is observed. Because of the mosaic of the cones and the constancy of this pattern of connectivity a model can be constructed where the dendritic fields of the cone horizontal cells overlap to a considerable extent. From this model, it follows that each double cone pedicle is contacted by four different horizontal cells. The functional significance of these findings for color vision is discussed in the light of recent work with the microspectrophotometer characterizing the cone system of this species as bichromatic. The mosaiclike arrangement of the horizontal cell dendrites supports the conclusion that the parallels between the patterns of receptor and horizontal cells are no coincidence but play an important role in lateral inhibition and neural adaptation of the retina.A preliminary report of this study was given at the international symposium Neural principles in vision held at the University of Munich in September 1975Supported by grant Wa 348/1 of the Deutsche Forschungsgemeinschaft     

Modeling of a Developing Planar Network of Cortical Neurons for Studying the Effects of Pharmacologically Modified Synaptic Connectivity on Cell Rhythmogenesis

A software tool for studying neural networks grown on planar substrates is described. The tool provides: (i) modeling the neuritic fields of individual neurons and their dynamic connectivity, (ii) creation of templates, cloning and connecting multiple instances of the neurons, (iii) computing the cellular electrical activity and Ca²⁺ dynamics, and (iv) estimating synchronization of the networked cells. Examples are shown of employing this tool for the study of synchronization of burst discharges in a network of the cortical neurons, whose connectivity is modified by neuropsin.     

Endocrine cells in the human fetal small intestine

Summary In this report we describe the time of appearance and ultrastructural features of enteroendocrine cells (EECs) in the human fetal small intestine (SB) between 9 and 22 weeks gestation. Thirteen distinctive EECs were identified in fetal SB. Two of these, not found in normal adult SB, appeared within the stratified epithelium of the proximal SB at 9–10 weeks. They were arbitrarily termed primitive and precursor cells. As in all fetal EECs, the pale cytoplasm of the primitive cell contains a distinctive population of secretory granules (SGs). Primitive cell SGs average 200–330 nm; some have dense cores with lucent halos while others are filled with a homogeneous dense or flocculent material. The SGs of the precursor cells are larger, averaging up to 1 m in diameter and their contents vary in electron density. A third group of cells not described in normal adult SB was arbitrarily termed transitional cells. These have two populations of SGs; one resembles the SGs of the precursor cells, and the other resembles the SGs of some of the specific adult type EECs. Transitional EC, S, I and G cells are seen. In addition, mature appearing EC, S, G, I, L, D, and D₁ cells were identified by 12 weeks of gestation. The primitive, precursor, and transitional cells may represent sequential developmental precursors of adult type EECs.Supported by Research Grant AM-17537 from the National Institutes of Health, Besthesda, MarylandThe authors would like to thank Ms. Linda Barstein for her excellent technical assistance     

Characterization of gangliosides from Ehrlich ascites tumour cells and their variants

Differences in the nature of the gangliosides present in two types of Ehrlich ascites tumour (EAT) cells, the adherent and non-adherent EAT cells, were studied. Gangliosides were isolated by DEAE Sephadex column chromatography and analysed by high-performance thin-layer chromatography (HPTLC). The non-adherent EAT (na-EAT) cells which grow in the peritoneal cavity of mice were selected for growth on basement membrane and tissue culture plastic to give the adherent EAT (a-EAT) cells. na-EAT cells contained 1.57 nmol lipid-bound sialic acid per mg protein and at least 12 different gangliosides, including major gangliosides such as GM3, GM2, GM1, GD3, GD1a and GT1b. On the other hand, the ganglioside pattern of a-EAT cells differed significantly from that of na-EAT cells, both quantitatively and qualitatively. The content of lipid-bound sialic acid in a-EAT cells was only 0.24 nmol per mg of protein. The gangliosides in a-EAT cells were characterized as GD1a and trisialogangliosides and, significantly, a-EAT cells did not contain monosialogangliosides. Neutral glycolipids were isolated from both cell lines and their patterns were compared. In contrast to the gangliosides pattern, their neutral glycolipid patterns were similar. Glucosylceramide and lactosylceramide were the major components in both types of cells. In addition to na- and a-EAT cells, a-EAT cells were passaged in mice by intraperitoneal injection, giving rise to a third variant (c/m EAT cells). We analysed the gangliosides in c/m EAT cells to determine whether there was a change in the ganglioside pattern found in na-EAT cells. After repeated passage of c/m EAT cells in mice, the pattern of gangliosides shifted to that of na-EAT cells. Alterations of ganglioside composition may be associated with the growth environment of the murine peritoneal cavity; alternatively, a selection process may have occurred.Abbreviations EAT cells Ehrlich ascites tumour cells - na-EAT cells non-adherent EAT cells - a-EAT cells adherent EAT cells - c/m EAT cells cultured a-EAT cells passaged in mice - HPTLC high-performance thin-layer chromatography - PBS 10 mM phosphate-buffered saline, pH 7.2, containing 0.15 M NaCl - EDTA ethylene-diaminetetraacetic acid - TFA trifluoroacetic acid - TG thioglycollate - Cer ceramide (N-fatty acyl sphingosine) - GM3 NeuAc2-3Gal1-4Glc-Cer - GM2 GalNAc1-4(NeuAc2-3)Gal1-4Glc-Cer - GM1a Gal1-3GalNAc1-4(NeuAc2-3)Gal1-4Glc-Cer - GD3 NeuAc2-8NeuAc2-3Gal1-4Glc-Cer - GD1a NeuAc2-3Gal1-3GalNAc1-4(NeuAc2-3)Gal1-4Glc-Cer - GT1b NeuAc2-3Gal1-3GalNAc1-4(NeuAc2-8NeuAc2-3)Gal1-4Glc-Cer - LacCer Gal1-4Glc-Cer - Gb3 Gal1-4Gal1-4Glc-Cer - Gb4 GalNAc1-4Gal1-4Gal1-4Glc-Cer This paper is dedicated to my esteemed colleague, Sen-itiroh Hakomori on the occasion of his 65th birthday.     

Edge preference of retinal and tectal neurons in common toads (Bufo bufo) in response to worm-like moving stripes: the question of behaviorally relevant ‘position indicators’

Summary Previous experiments have shown that during prey-catching behavior (orienting, snapping) in response to a worm-like moving stripe common toads.Bufo bufo (L.) exhibit a contrast-and direction-dependent edge preference. To a black (b) stripe moving against a white (w) background (b/w), they respond (R^*) preferably toward the leading (l) rather the trailing (t) edge (R _l ^* > R _t ^* ), thus displaying head preference. If the contrastdirection is reversed (w/b), the stripe's trailing edge is preferred (R _l ^* < R _t ^* ), hence showing tail preference. In the present study, neuronal activities of retinal classes R2 and R3 and tectal classes T5(2) and T7 have been extracellularly recorded in response to leading and trailing edges of a 3 ° × 30 ° stripe simulating a worm and traversing the centers of their excitatory receptive fields (ERF) horizontally at a constant angular velocity in variable movement direction (temporo-nasal or naso-temporal).The behavioral contrast-direction dependent edge preferences are best resembled by the responses (R) of prey-selective class T5(2) neurons (R_l R_t=101 for b/w, 0.31 for w/b) and T7 neurons (R_lR_t=61 for b/w, 0.41 for w/b); the T7 responses may be dendritic spikes. This property can be traced back to off-responses dominated retinal class R3 neurons (R_lR_t=61 for b/w, 0.51 for w/b), but not to class R2 (R_lR_t =1.21 for b/w and 0.91 for w/b). The respective edge preference phenomena are independent of the direction of movement.When stimuli were moved against a stationary black-white structured background, the head preference to the black stripe and the tail preference to the white stripe were maintained in class R3, T5(2), and T7 neurons. If the stripe traversed the ERF together with the structured background in the same direction at the same velocity, the responses of tectal class T5(2) and T7 neurons were strongly inhibited, particularly in the former. Responses of retinal R2 neurons in comparable situations could be reduced by about 50%, while class R3 neurons responded to both the stimulus and the moving background structure.The results support the concept that the prey feature analyzing system in toads applies principles of (i) parallel and (ii) hierarchial information processing. These are (i) divergence of retinal R3 neuronal output contributes to stimulus edge positioning and (in combination with R2 output) area evaluation intectal neurons and to stimulus area evaluation and (in combination with R4 output) sensitivity for moving background structures inpre tectal neurons; (ii) convergence of tectal excitatory and pretectal inhibitory inputs specify the property of prey-selective tectal T5(2) neurons which are known to project to bulbar/spinal motor systems.Abbreviations ERF excitatory receptive field - IRF inhibitory receptive field - N nasal - T temporal - R _w response to a worm-like stripe moving in the direction of its longer axis - R _A response to an antiworm-like stripe whose longer axis is oriented perpendicular to the direction of movement - R _l response to the leading edge of a worm-like moving stripe - R _t response to the trailing edge of a worm-like moving stripe - b/w black stimulus against a white background - w/b white stimulus against a black background - sm structured moving background - ss structured stationary background - u minimal structure width of a structured background consisting of rectangular black and white patches in random distribution - HRP horseradish peroxidase     

Ein Kreislauforgan bei Kamptozoen

Zusammenfassung Alle koloniebildenden Kamptozoen (Pedicelliniden, Barentsiiden und Urnatelliden) besitzen in der verengten Halszone an der Kelch-Stielgrenze ein Aggregat tellerartig flacher Muskelzellen, die — in einem Stapel übereinander angeordnet — den Stiel septenartig quer durchspannen. Sie sind kelchwärts gewölbt und erscheinen in der Aufsicht sternförmig verzweigt. Im lebenden Tier führt dieser Zellkomplex ständig rhythmische Kontraktionen aus und preßt dadurch Gewebsflüssigkeit vom Kelch in den Stiel. An 5 Arten, Urnatella gracilis, Barentsia benedeni, Barentsia laxa, Barentsia discreta und Barentsia cf. gracilis, wird die Ultrastruktur dieser Muskelzellen und die Architektur von Stielhals und Sternzellgewölbe unter Berücksichtigung funktioneller Gesichtspunkte untersucht und eingehend beschrieben. Die morphologischen Befunde werden im Hinblick auf die physiologischen Bedürfnisse der Tiere und auf ihre mögliche Bedeutung diskutiert und mit den Verhältnissen bei solitär lebenden Kamptozoen verglichen. Der Sternzellapparat ist offenbar ein Herzäquivalent, welches der Zone aktivsten Baustoffwechsels, dem apikalen Stielraum, ständig nährstoffreiche Hämolymphe aus dem Kelch zuführt. Diese Zirkulation von Gewebsflüssigkeit hat wahrscheinlich nur nutritive Aufgaben. Der Austausch von Atemgasen erfolgt vermutlich über Mikrovilli der Außenepithelzellen, die überall an der Körperoberfläche durch die Cuticula hindurch mit dem Umgebungsmedium in Kontakt stehen.

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A circulatory organ in entoprocta

Summary All colonial type entoprocta (Pedicellinidae, Barentsiidae and Urnatellidae) have in the narrow zone between calyx and stalk a stack of flat star-like branched muscle cells, the uppermost of which is canopy shaped whereas the subsequent cells gradually flatten out. All these muscle cells are septum-like, being stretched out across the central hollow of the apical end of the stalk. They are attached to the body wall by their points. By rhythmical contractions they pump tissue fluid from the basal portion of the calyx into the stalk. In five different species of colony building entoprocta — Urnatetta gracilis, Barentsia benedeni, Barentsia laxa, Barentsia discreta and Barentsia cf. gracilis — the architecture of the upper end of the stalk, the ultrastructure of the so called star cells and their function has been investigated. The morphological results are discussed with respect to the physiological requirements of these animals and their possible significance, and are further compared with the conditions in solitary type entoprocta, which lack the star cell apparatus. The conclusions indicate a biological advantage in evolving of a heart-like organ to provide the stalk — which in colony type entoprocta is the budding center — with the nutrient hemolymphe. This primitive circulatory system has a nutritional function. The exchange of respiratory gases probably takes place through microvilli of the outer epithelial cells, which connect the entire body surface with the surrounding medium.

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Die Untersuchungen wurden von der Deutschen Forschungsgemeinschaft in dankenswerter Weise gefördert.     

Habituation rules for a theory of the cerebellar cortex

A quantitative model of cerebellar cortical function is described with a complete formalization based on (i) the topology of cerebellar cortical neuronal network, (ii) some particular synaptic properties of cell classes in cerebellum cortex, and (iii) the dynamics of excitation in this network. For (i), a construction of functional classes around one Purkinje cell is given and their existence is discussed. For (ii), as in Marr-Albus model, the modifiability of synapses between parallel fibres and Purkinje cell is assumed. But the formalization permits to consider the consequences of such a property at the level of glomerulus (with granule cells) which is known as a complex transformation system. For (iii) habituation rules are assumed. It is shown that this method leads to some interesting properties in the functioning of cerebellar cortex. Particularly, emitting frequency along a Purkinje cell axon results from a discrimination by the system between transformed input signals and an external noise due to all other contexts, and learning could be considered as the result of a conflict between a set of patterns and the transformed input signals. This model could be a basis for future numerical simulations.     

Role of MMP-2 in inhibiting Na+ dependent Ca2+ uptake by H2O2 in microsomes isolated from pulmonary smooth muscle

Treatment of microsomes (preferentially enriched with endoplasmic reticulum) isolated from bovine pulmonary artery smooth muscle tissue with H₂O₂ (1 mM) markedly stimulated matrix metalloproteinase activity and also inhibited Na⁺ dependent Ca²⁺ uptake. Electron micrograph revealed that H₂O₂ (1 mM) does not cause any damage to the microsomes. MMP-2 and TIMP-2 were determined to be the ambient protease and corresponding antiprotease of the microsomes. Pretreatment with vitamin E (1 mM) and TIMP-2 (50 g/ml) reversed the effect produced by H₂O₂ (1 mM) on Na⁺ dependent Ca²⁺ uptake in the microsomes. However, H₂O₂ (1 mM) caused changes in MMP-2 activity and Na⁺ dependent Ca²⁺ uptake were not reversed upon pretreatment of the microsomes with a low concentration of 5 g/ml of TIMP-2 which otherwise reversed MMP-2 (1 g/ml) mediated increase in ¹⁴C-gelatin degradation and inhibition of Na⁺ dependent Ca²⁺ uptake. Combined treatment of the microsomes with a low dose of MMP-2 (0.5 g/ml) and H₂O₂ (0.5 mM) inhibited Na⁺ dependent Ca²⁺ uptake in the microsomes compared to the respective low dose of either of them. Direct treatment of TIMP-2 (5 g/ml) with H₂O₂ (1 mM) abolished the inhibitory effect of the inhibitor on ¹⁴C-gelatinolytic activity elicited by 1 g/ml of MMP-2. Thus, one of the mechanisms by which H₂O₂ activates MMP-2 could be due to inactivation of TIMP-2 by the oxidant. The resulting activation of MMP-2 subsequently inhibits Na⁺ dependent Ca²⁺ uptake in the microsomes. (Mol Cell Biochem 270: 79–87, 2005)     

Age-related accumulation of lysosomes and other cytological features in active thyroid follicles of the CBA mouse

Summary This study attempts to elucidate the mechanism through which lysosomal accumulation occurs with age in the epithelial cells of the thyroid gland and especially in the active follicles of the aging mouse thyroid. Thyroid morphology and function in old CBA (at least 24 months of age) male mice were compared with those in young (2 months of age) animals. The effects of different intake of iodine were tested and compared in both cohorts, each of which was divided into three groups: (i) low iodine group, (ii) moderate iodine group, and (iii) high iodine group. As expected, the present work confirmed the well-known accumulation with age of cold follicles coexisting with active follicles in the old mouse thyroid. Attention has been focused on the active follicles whose follicular cells contained in their cytoplasm a large number of pleomorphic dense bodies. The lysosomal nature of these bodies, referred to as secondary lysosomes, was confirmed by histochemistry; however, they displayed variability in acid phosphatase staining. In old animals, regardless of the type of iodine regimen, the ratio between relative follicular volume and relative colloid volume as determined by morphometry remained unchanged. Ultrastructurally, the relative volume occupied by secondary lysosomes in active follicles was always higher than in the young groups. Autoradiographic studies with ¹²⁵I revealed that a large part of the radioactivity was located in secondary lysosomes of thyroid cells in active follicels of old mice when radioiodine was injected 3 weeks before death. Two different types of vacuoles were present in a non-negligible number of thyrocytes of the active follicles in aged cohorts. The first type was made up of grossly dilated rough endoplasmic cisternae, the second corresponded to intracytoplasmic microfollicular vacuoles. Both aspects have been described in conditions of chronic stimulation. It is concluded (1) that different intake of iodine for 6 weeks does not modulate the thyroid morphology in old mice; (2) that in the thyrocytes of the active follicles in old mice accumulation of secondary lysosomes occurs due to a slowdown of turnover; and (3) that the follicular cells of active follicles feature morphological aspects suggesting a hyperactive state compensating the lack of hormone production in the cold follicles.     

A self-organizing neural network with a function of associative memory: Feedback-type cognitron

Previously, one of the authors proposed a new hypothesis on the organization of synaptic connections, and constructed a model of self-organizing multi-layered neural network cognitron (Fukushima, 1975). the cognitron consists of a number of neural layers with similar structure connected in a cascade one after another. We have modified the structure of the cognitron, and have developed a new network having an ability of associative memory. The new network, named a feedback-type cognitron, has not only the feedforward connections as in the conventional cognitron, but also modifiable feedback connections from the last-layer cells to the front-layer ones. This network has been simulated on a digital computer. If several stimulus patterns are repeatedly presented to the network, the interconnections between the cells are gradually organized. The feedback connections, as well as the conventional feedforward ones, are self-organized depending on the characteristies of the externally presented stimulus patterns. After adequate number of stimulus presentations, each cell usually acquires the selective responsiveness to one of the stimulus patterns which have been frequently given. That is, every different stimulus pattern becomes to elicit an individual response to the network. After the completion of the self-organization, several stimulus patterns are presented to the network, and the responses are observed. Once a stimulus is given to the network, the signal keeps circulating in the network even after cutting off the stimulus, and the response gradually changes. Even though an imperfect or an ambiguous pattern is presented, the response usually converges to one of the patterns which have been frequently given during the process of self-organization. In some cases, however, a new pattern which has never been presented before, emerges. It is seen that this feedback-type cognitron has characteristics quite similar to some functions of the brain, such as the associative recall of memory, or the creation of a new idea by intuition.