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PubMed1977

Genetically-associated variations in the development of hippocampal pyramidal neurons may produce differences in mossy fiber connectivity.

The neuronal generation patterns of hippocampal pyramids were analyzed in two inbred strains of house mice (SM/J and BALB/cJ) using triated thymidine radioautography. These two strains of mice possess markedly different patterns of mossy fiber synapses upon pyramidal neurons within a specific segment of regio inferior. The results of this study show that this same segment of regio inferior also displays markedly different patterns of pyramidal neuron generation in the two strains. Specifically, the pyramids of this segment of regio inferior are generated according to the typical "inside-out" sequence in SM/J mice, but this pattern is reversed into an "outside-in" sequence in BALB/cJ mice. Remaining segment of regio inferior, and all of regio superior, is formed in an inside-out sequence in both strains. These results strongly suggest that altered temporal patterns of pyramidal neuron generation may play a major role in determining mossy fiber connectivity patterns.

Animals↗
PubMed1999

Graft-host connections in long-term full-thickness embryonic rabbit retinal transplants.

PURPOSE: To establish neuronal connections in the rod and cone pathway between laminated rabbit retinal transplants and the host retina. METHODS: Fourteen adult rabbits received a complete full-thickness embryonic transplant. After survival times of 3 to 10 months, the retinas were studied under light microscope and with immunohistochemistry. Antibodies against protein kinase C (PKC), parvalbumin, and calbindin were used to label rod bipolar cells, AII amacrine cells, and cone bipolar cells, respectively. The AB5 antibody was used to label ganglion cells. RESULTS: The transplants displayed laminated morphology with layers parallel to the host retinal pigment epithelium. In the oldest specimens (10 months after surgery), laminated layers of graft and host approached each other and almost reconstructed the normal retinal appearance. The ganglion and cone bipolar cells of the host survived well, as was seen with AB5 and calbindin double-labeling. Connections between cone bipolar cells in the graft and ganglion cells in the host were not common. PKC-labeled rod bipolar cells and parvalbumin-labeled AII amacrine cells of host and graft showed sprouting activity directed toward an intermediate plexiform layer located between the graft and host. In specimens double-labeled with PKC and parvalbumin, this intermediate plexiform layer was seen to contain numerous PKC- and parvalbumin-labeled processes. Direct connections between rod bipolar and AII amacrine cells in host and graft were seen in the 10-month specimens. CONCLUSIONS: Full-thickness embryonic transplants survive for at least 10 months, and normal laminated morphology develops. Host and graft fuse and together contribute nerve cell processes to an intermediate plexiform layer. Direct graft-host contacts are also present between neuronal types that in the normal retina participate in the rod pathway.

Animals↗
PubMed2002

Making connections in the fly visual system.

Understanding the molecular mechanisms that regulate formation of precise patterns of neuronal connections within the central nervous system remains a challenging problem in neurobiology. Genetic studies in worms and flies and molecular studies in vertebrate systems have led to an increasingly sophisticated understanding of how growth cones navigate toward their targets and form topographic maps. Considerably less is known about how growth cones recognize their cellular targets and form synapses with them. Here, we review connection formation in the fly visual system, the methodological approaches used to study it, and recent progress in uncovering the molecular basis of connection specificity.

Animals↗
PubMed2003

[The structure of internal intraneuronal connections in the area 17 of the cat cerebral cortex].

Spatial distribution of horizontal intrinsic neuronal connections in area 17 of cat cerebral cortex was studied following HRP microion tophoretic injections into the single cortical columns. Cluster analysis of labelled cell distribution in superficial layers was performed in the tangential cortical plane. Area 17 was found to contain 7 +/- 1 clusters each consisting of 1-5 cells. Clusters were arranged in two rows, separated by a distance of 1.2 +/- 0.3 mm. The distance between the centers of the clusters that form the rows was equal to 0.8 +/- 0.3 mm. The spatial characteristics of cell clusters sending axons to cortical column, found in this study, were compared with the known data on the optical imaging of the activity of neurons of orientation and ocular dominance columns of visual cortex. It is suggested that area 17 cortical column receives inputs from cells of 6-8 hypercolumns that have similar ocular dominance and orientation preference.

Animals↗
PubMed2007

Modelling memory functions with recurrent neural networks consisting of input compensation units: I. Static situations.

Humans are able to form internal representations of the information they process -- a capability which enables them to perform many different memory tasks. Therefore, the neural system has to learn somehow to represent aspects of the environmental situation; this process is assumed to be based on synaptic changes. The situations to be represented are various as for example different types of static patterns but also dynamic scenes. How are neural networks consisting of mutually connected neurons capable of performing such tasks? Here we propose a new neuronal structure for artificial neurons. This structure allows one to disentangle the dynamics of the recurrent connectivity from the dynamics induced by synaptic changes due to the learning processes. The error signal is computed locally within the individual neuron. Thus, online learning is possible without any additional structures. Recurrent neural networks equipped with these computational units cope with different memory tasks. Examples illustrate how information is extracted from environmental situations comprising fixed patterns to produce sustained activity and to deal with simple algebraic relations.

Humans↗
PubMed2004

Coordinated functions of Netrin-1 and Class 3 secreted Semaphorins in the guidance of reciprocal septohippocampal connections.

An essential characteristic of the CNS function is the formation of reciprocal connections between brain areas. Although the mechanisms controlling the establishment of neuronal connections are being determined, very little is known about the development of reciprocal connections, which often course along identical pathways. Here, we show that Netrin-1, expressed along the fimbria, chemoattracts both septohippocampal and hippocamposeptal fibers. Moreover, we show that both Semaphorins 3A and 3F expressed in regions nearby the septum prevent the growth of septal axons into these regions. Blocking experiments with recombinant ecto-Neuropilins indicate that both Semaphorins 3A and 3F act cooperatively in the repulsion of septal axons. Furthermore, netrin-1-deficient mice develop a reduced septohippocampal projection. We conclude that the coordinated actions of Netrin-1 and Semaphorins 3A and 3F cooperate in the development of septohippocampal and hippocamposeptal connections, indicating that the same molecular cues serve the construction of reciprocal connections in both directions of growth.

Animals↗
PubMed1998

Analysis of the signals generated by networks of neurons coupled to planar arrays of microtransducers in simulated experiments.

Planar microelectrode arrays can be used to characterize the dynamics of networks of neurons reconstituted in vitro. In this paper simulations related to experiments of the electrical activity recording by means of planar arrays of microtransducers coupled to networks of neurons are described. First a detailed model of single and synaptically connected neurons is given, appropriate to computer simulate the action potentials of neuronal populations. Then 'realistic' signals are generated. These signals are intended to reproduce, both in shape and intensity, those recorded by a microelectrode array. Typical experimental conditions are considered, and a detailed analysis given, of the bioelectronic coupling and of its influence on the shape of the recorded signals. Finally, simulated experiments dealing with dorsal root ganglia neurons are described and analysed in comparison with experimental results reported in the literature and obtained in our own laboratory. The effectiveness of the planar microelectrode technique is briefly discussed.

Animals↗
PubMed2001

Activation of microglia by secreted amyloid precursor protein evokes release of glutamate by cystine exchange and attenuates synaptic function.

Microglial activation as part of a chronic inflammatory response is a prominent component of Alzheimer's disease. Secreted forms of the beta-amyloid precursor protein (sAPP) previously were found to activate microglia, elevating their neurotoxic potential. To explore neurotoxic mechanisms, we analyzed microglia-conditioned medium for agents that could activate glutamate receptors. Conditioned medium from primary rat microglia activated by sAPP caused a calcium elevation in hippocampal neurons, whereas medium from untreated microglia did not. This response was sensitive to the NMDA receptor antagonist, aminophosphonovaleric acid. Analysis of microglia-conditioned by HPLC revealed dramatically higher concentrations of glutamate in cultures exposed to sAPP. Indeed, the glutamate levels in sAPP-treated cultures were substantially higher than those in cultures treated with amyloid beta-peptide. This sAPP-evoked glutamate release was completely blocked by inhibition of the cystine-glutamate antiporter by alpha-aminoadipate or use of cystine-free medium. Furthermore, a sublethal concentration of sAPP compromised synaptic density in microglia-neuron cocultures, as evidenced by neuronal connectivity assay. Finally, the neurotoxicity evoked by sAPP in microglia-neuron cocultures was attenuated by inhibitors of either the neuronal nitric oxide synthase (N(G)-propyl-L-arginine) or inducible nitric oxide synthase (1400 W). Together, these data indicate a scenario by which microglia activated by sAPP release excitotoxic levels of glutamate, probably as a consequence of autoprotective antioxidant glutathione production within the microglia, ultimately causing synaptic degeneration and neuronal death.

2-Aminoadipic Acid↗
PubMed2004

Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex of alert mice.

Oscillations in neuronal populations may either be imposed by intrinsically oscillating pacemakers neurons or emerge from specific attributes of a distributed network of connected neurons. Calretinin and calbindin are two calcium-binding proteins involved in the shaping of intraneuronal Ca2+ fluxes. However, although their physiological function has been studied extensively at the level of a single neuron, little is known about their role at the network level. Here we found that null mutations of genes encoding calretinin or calbindin induce 160 Hz local field potential oscillations in the cerebellar cortex of alert mice. These oscillations reached maximum amplitude just beneath the Purkinje cell bodies and are reinforced in the cerebellum of mice deficient in both calretinin and calbindin. Purkinje cells fired simple spikes phase locked to the oscillations and synchronized along the parallel fiber axis. The oscillations reversibly disappeared when gap junctions or either GABA(A) or NMDA receptors were blocked. Cutaneous stimulation of the whisker region transiently suppressed the oscillations. However, the intrinsic somatic excitability of Purkinje cells recorded in slice preparation was not significantly altered in mutant mice. Functionally, these results suggest that 160 Hz oscillation emerges from a network mechanism combining synchronization of Purkinje cell assemblies through parallel fiber excitation and the network of coupled interneurons of the molecular layer. These findings demonstrate that subtle genetically induced modifications of Ca2+ homeostasis in specific neuron types can alter the observed dynamics of the global network.

Action Potentials↗
PubMed1998

Nervous network in larvae of the ascidian Ciona intestinalis.

With the use of the monoclonal antibody UA301, which specifically recognizes the nervous system in ascidian larvae, the neuronal connections of the peripheral and central nervous systems in the ascidian Ciona intestinalis were observed. Three types of peripheral nervous system neurons were found: two located in the larval trunk and the other in the larval tail. These neurons were epidermal and their axons extended to the central nervous system and connected with the visceral ganglion directly or indirectly. The most rostral system (rostral trunk epidermal neurons, RTEN) was distributed bilateral-symmetrically. In addition, presumptive papillar neurons in palps were found which might be related to the RTEN. Another neuron group (apical trunk epidermal neurons, ATEN) was located in the apical part of the trunk. The caudal peripheral nervous system (caudal epidermal neurons, CEN) was located at the dorsal and ventral midline of the caudal epidermis. In the larval central nervous system, two major axon bundles were observed: one was of a photoreceptor complex and the other was connected with RTEN. These axon bundles joined in the posterior sensory vesicle, ran posteriorly through the visceral ganglion and branched into two caudal nerves which ran along the lateral walls of the caudal nerve tube. In addition, some immunopositive cells existed in the most proximal part of the caudal nerve tube and may be motoneurons.

Animals↗
PubMedDate not supplied

A mathematical approach to the connectivity between the cortical visual areas of the macaque monkey.

The visual cortex of the macaque monkey is divided into many distinct visual information processing areas. In many cases, anatomical and physiological results allow one to determine the presence or the absence of neuronal connections from one area to another. We have approached the topology of this neuronal network within the mathematical framework of graph theory. At first, we studied the unknown part of the network, i.e. the part where anatomical and physiological results are lacking. Relying on a specific topological property of the network established on the known part, we developed an interpolation algorithm for reducing the level of uncertainty concerning the unknown part. From these results, we then constructed a connectional model of the neuronal network for the entire cortical visual system. Subsequently, a topological analysis of this model, with the help of factorial analysis and clustering technics, shows its structural properties and singular vertices. This analysis suggests the existence of two distinct classes of areas, one in the parietal part of the cortex and the other in the temporal part, which are connected to each other via relay areas, especially involving the frontal eye field. These results may help to understand the functional role of particular cortical areas in vision and, more generally, to explore how visual information flows within the visual cortex.

Algorithms↗
PubMed2005

Developmental modifications of olivocerebellar topography: the granuloprival cerebellum reveals multiple routes from the inferior olive.

Correct function of neural circuits depends on highly organized neuronal connections, refined from less precise projections through synaptic elimination, collateral regression, or neuronal death. We examined regressive phenomena that define olivocerebellar topography during maturation from Purkinje cell polyinnervation to monoinnervation. We used bilateral retrograde tracing to determine the source of olivocerebellar afferents to posterior vermis lobules VII-VIII in a model of retained immature Purkinje cell polyinnervation, the granuloprival cerebellum. In controls, labelled neurons were found only in the contralateral inferior olive (ION) clustered in a small ventromedial locus that is congruent with known olivocerebellar topography. In granuloprival animals, olivary labelling appeared more dispersed and was present in homologous ipsilateral regions. Double-labelled neurons were never seen. Retrograde tracing following unilateral olivocerebellar transection in adult granuloprival rats revealed: 1) the origin of the normal (remaining) path projecting through the contralateral inferior peduncle was more localized than in irradiated nonpedunculotomized rats, 2) a small double-crossed path, and 3) a projection that ascends the peduncle ipsilateral to the ION of origin, part of which crosses the midline within the cerebellum. Electrophysiological and immunohistochemical assessment in the neonatal cerebellum revealed that transcommissural paths are not present during development but sprout within the irradiated cerebellum. Therefore, the olivocerebellar projection in the granuloprival rat, as a model of the immature path, shows parasagittal organization similar to that of controls in its normally crossed path but possesses additional abnormal projections. Thus, maturation of olivocerebellar topography involves removal of whole developmental paths to define laterality plus synapse elimination within largely predefined parasagittal zones.

Animals↗
PubMed1977

Types and arrangements of neurons in the crayfish optic lamina.

The neural arrangements in the optic lamina of the crayfish Pacifastacus leniusculus Dana have been studied by light microscopy by means of silver impregnation techniques. The lamina is composed of columnar synaptic compartments (cartridges). Each cartridge is composed of seven receptor terminals distributed in two layers and second-order monopolar neurons connecting the lamina with the second synaptic region, the medulla externa. The neurons found in the lamina consist of five classes: monopolar neurons, centrifugal small-field neurons, tangential neurons, multipolar cells (possibly of a glial nature) and photoreceptor axons (fig. 13). Among the monopolar cells, five types are classified (M1-M5) according to their lamina arborizations. Two types are stratified (M3 and M5) corresponding to the photoreceptor terminal strata. On this basis, the lamina plexiform layer is subdivided into two layers (epl1 and epl2). The remaining monopolar neurons have lateral processes in both layers, two of them within one cartridge (M1 and M2) and one over several cartridges (M5). There is one type of small-field centrifugal neuron (C1) and two types of tangential medulla to lamina neurons (Tan1 and Tan2), both having processes covering a large number of cartridges. Multipolar cells with cell bodies distal (MP1) or proximal (MP2) to the plexiform layer send processes to several cartridges. The receptor axons consit of three types. One has terminals in epl1 or epl2, the second has its terminal in epl1 and a thin process to epl2, and the third (corresponding to the 8th retinular cell) bypasses the lamina and has a terminal in the medulla externa. A brief comparison is made with the neural arrangements in the lamina of the Norway lobster Nephrops norvegicus L.

Animals↗
PubMed1993

A central nervous system keratan sulfate proteoglycan: localization to boundaries in the neonatal rat brain.

During the development of the central nervous system (CNS), adhesive molecules promote the formation of axonal pathways and appropriate neuronal connections by facilitating cellular interactions. In addition to the interactions that bring neurons together, recent evidence suggests inhibition of neuronal interactions also plays a role by restricting axons to their appropriate pathways and forming boundaries between functional units of the developing CNS. The present study describes the distribution of a recently identified large keratan sulfate proteoglycan, ABAKAN, in the postnatal day 14 (P14) and adult rat brain. In the adult brain ABAKAN appears to be relatively evenly distributed throughout the CNS, while at P14 this proteoglycan is found at high concentrations between different functional units of the neonatal brain. For example, ABAKAN appears to separate different cortical areas and mark the boundaries between thalamic nuclei. In vitro assays demonstrate that this keratan sulfate proteoglycan is a potent inhibitor of neurite growth. The distribution of ABAKAN at P14 and the effects of this keratan sulfate proteoglycan on neurite growth suggest that ABAKAN functions as a molecular barrier to axonal growth in the developing rat brain.

Aging↗
PubMedDate not supplied

Dendritic spine loss in hippocampus of aged rats. Effect of brain phosphatidylserine administration.

Dendritic spine density of pyramidal cells in region CA1 of the hippocampus has been evaluated in young (3 months), old (27 months) and old phosphatidylserine (BC-PS)-treated rats. BC-PS (50 mg/kg, suspended in tap water) was administered daily, starting at the age of 3 months until 27 months. Spine density was analyzed on Golgi-stained pyramidal neurons by a computerized analysis system. In 27-month-old rats, spine density showed with respect to 3-month-old animals, a significant decrease in both basal and apical dendrites (p less than 0.01; one-way ANOVA), with a mean loss of 12.11% in the basal dendrites and of 10.64% in the apical ones. In 27-month-old rats treated with BC-PS, values of spine density were not statistically different when compared to those of 3-month-old animals. The mechanisms underlying the beneficial effect of BC-PS treatment on neuronal connectivity might be explained on the basis of its pharmacological actions on neuronal membranes [9], neurotransmission [43] and/or interaction with NGF [7].

Aging↗
PubMed1991

Noradrenergic locus coeruleus neurons: their distant connections and their relationship to neighboring (including cholinergic and GABAergic) neurons of the central gray and reticular formation.

Noradrenergic LC neurons appear to be relatively unique in the brain, being unsurpassed in the divergence and ubiquity of their projections through the central nervous system. In this regard, they share certain characteristics with peripheral noradrenaline neurons of the sympathetic nervous system. As such they would be assumed to play a very general role in modulating the activity of large populations of neurons in multiple, functionally diverse systems. Like other periventricular and reticular neurons, they have the potential to receive afferent information from multiple sources via long dendrites, upon which the majority of their inputs from brainstem and forebrain may arrive. They appear closely related to the cholinergic neurons of the laterodorsal tegmental nucleus, their neighbors that are located medial and rostral to them within the periventricular gray and that have similarly oriented and positioned long dendrites that would allow reception of similar afferent input as the LC neurons and also possibly interaction with the LC neurons. As evidenced by input to the noradrenergic cell bodies in the compact portion of the nucleus, a moderate GABAergic innervation, that may derive in part from local neurons, could have a potent influence on the activity of the cells. Periventricular GABAergic cells could also serve as intermediaries to other afferent input, from a distance, terminating in the periventricular region or from local neurons such as the cholinergic cells of the laterodorsal tegmental nucleus.

Acetylcholine↗
PubMed2002

Visualizing selective neural pathways with WGA transgene: combination of neuroanatomy with gene technology.

Functional logic employed by the nervous system for information processing resides mainly in the wiring patterns among specific types of neurons. Therefore, detailed knowledge on neuronal networks is essential for understanding a wide range of brain functions. A powerful and long-awaited method for analyzing the neuronal connectivity patterns would be to deliver tracers selectively to specific types of neurons and at the same time to label transsynaptically their axonal target neurons. For this purpose, we took advantage of a unique property of plant lectin, wheat germ agglutinin (WGA), which has been used as a transsynaptic tracer in classical neuroanatomical studies. We developed a novel genetic strategy that employs WGA cDNA as a transgene, for the visualization of selective and functional neural pathways in the nervous system. In this article, I will introduce several examples of neural pathways visualized with the WGA transgene and discuss about its further refinement and applications.

Animals↗
PubMed2001

The role of Notch and Rho GTPase signaling in the control of dendritic development.

Dendritic patterning exerts a profound influence on neuronal connectivity. Recent studies indicate that mammalian Notch receptors are expressed by postmitotic neurons and that Notch signaling has a considerable influence on dendritic growth and branching. Investigations into the intracellular effectors of dendritic development have revealed that dendritic growth and branching are differentially affected by activation of the Rho-family GTPases, RhoA, Rac1, and Cdc42. These observations suggest that the differential activation of Notch receptors and Rho-family GTPases by extracellular signals may be important in the generation of morphological diversity in the developing nervous system.

Animals↗