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PubMed2002

Changes in the views of neuronal connectivity and communication after Cajal: examples from the hippocampus.

Intracellular recordings with concurrent visualization of the neuron as well as immunocytochemical studies in the last couple of decades confirmed the selectivity, and revealed additional complexity, in the synaptic connections in hippocampal circuits described by Santiago Ramón y Cajal. Even minor anatomical details began to gain functional meaning via the state-of-the-art combined approaches. The revolution of molecular biology brought about the rapid development of anatomy aimed at the localization of the numerous receptor subunits, ion channels, transporters and other proteins at the regional, cellular and subcellular levels that are being cloned every day (e.g., see Nusser, 2000). These fine-grain immunocytochemical data appear to have an immense predictive power for physiological and pharmacological studies and continue to serve as the ultimate test of hypotheses drawn from functional studies. Knowledge of the precise anatomical distribution of extrasynaptic receptors is required to understand the functional roles of various nonsynaptic mediators and diffuse pathways in the brain, as well as to the design of selective drugs for pharmacotherapy. Cajal would be delighted to see the revitalization of functional neuroanatomy, particularly of molecular anatomy, among the modern disciplines in the neurosciences today.

Animals↗
PubMed2002

Development of neuronal connectivity in Drosophila antennal lobes and mushroom bodies.

Recent advances in the study of the connectivity of Drosophila olfactory system include the demonstration that olfactory receptor neurons project to specific glomeruli according to the receptor type they express, and that their projection neuron partners are prespecified to innervate particular glomeruli by birth order or time. This same theme of sequential generation has been observed in the generation of the three major types of mushroom body neurons.

Animals↗
PubMed1988

Immunohistochemical localization of monoamines and cyclic nucleotides. Their application in quantitative immunofluorescence studies and tracing monoaminergic neuronal connections.

We have described immunocytochemical methods for the direct visualization of monoamine- and cGMP-containing neurons, using antibodies to the primary or secondary messengers themselves. The specificity and affinity of these antibodies were determined using quantitative immunofluorescence of gelatin models, as non-biological models, to which the native substances and their possibly cross-reacting compounds were incorporated. The use of retro- and anterograde tracers both in conjunction with immunohistochemical procedures provides the possibility to characterize transmitter specifically afferent and efferent pathways. With the presented double-label immunocytochemical procedures it is feasible to visualize and trace a projection between two brain areas, and in addition to specify the transmitters which are involved in their afferents and efferents and their target neurons and neurons of origin. Using the SCG, as a biological model, we could demonstrate that cGMP levels in individual cells could be elevated by cholinergic agonists. Moreover, using quantitative immunofluorescence of cGMP as a post- or presynaptic marker we have the possibility to measure the post-/presynaptic effects of monoamines or neuropeptides in individual neurons.

Animals↗
PubMed1997

Modifiable neuronal connections: an overview for psychiatrists.

Synaptic plasticity is currently the target of much neurobiological research, because it is thought to play an important role in brain function (particularly memory formation). However, it has attracted little attention from psychiatrists to date despite accumulating evidence that links it to various clinical syndromes, including amnesia and possibly psychosis. The purpose of this article is to present an overview of the two major arms of synaptic plasticity research-theoretical (the field of neural network modeling) and neurobiological (long-term potentiation). Artificial neural networks are a class of theoretical model that has been developed with the aim of understanding how information could, in principle, be represented by large numbers of interconnected and relatively simple units. Over the past few decades, several theoretical accounts of information-processing mechanisms have been developed, and these are briefly reviewed. The principle common to representation formation in nearly all neural networks is that of "associability"-the idea that streams of information are combined by forming, strengthening, or pruning connections between them to form new representations that can later be retrieved. Associability also lies at the heart of psychological theories of information storage in the brain. Research into associability has directed the attention of many experimenters toward the possible biological correlates of such mechanisms. Of particular interest is the recent discovery that some neurons appear to possess connections of modifiable strength. The implications of this finding for psychiatry are discussed in relation to representational disorders such as delusions and amnesia.

Amnesia↗
PubMed2004

Effects of brain-derived neurotrophic factor on cell survival, differentiation and patterning of neuronal connections and Müller glia cells in the developing retina.

The aim of the present study was to determine the influence of brain-derived neurotrophic factor (BDNF) on survival, phenotype differentiation and network formation of retinal neurons and glia cells. To achieve a defined concentration and constant level of BDNF over several days, experiments were performed in an organotypic culture of the developing rat retina. After 6 days in vitro, apoptosis in the different cell layers was determined by TUNEL staining and cell-type-specific antibodies were used to identify distinct neuronal cell types and Müller cells. Cultured retinas treated with BDNF (100 ng BDNF/mL medium) were compared with untreated as well as with age-matched in vivo retinas. Quantitative morphometry was carried out using confocal microscopy. BDNF promoted the in vitro development and differentiation of the retina in general, i.e. the number of cells in the nuclear layers and the thickness of the plexiform layers were increased. For all neurons, the number of cells and the complexity of arborizations in the synaptic layers were clearly up-regulated by BDNF. In control cultures, the synaptic stratification of cone bipolar cells within the On- and Off-layer of the inner plexiform layer was disturbed and a strong reactivity of Müller cell glia was observed. These effects were not present in BDNF-treated cultures. Our data show that BDNF promotes the survival of retinal interneurons and plays an important role in establishing the phenotypes and the synaptic connections of a large number of neuronal types in the developing retina. Moreover, we show an effect of BDNF on Müller glia cells.

Age Factors↗
PubMed1984

Crosscorrelation analysis of intracolumnar neuronal connectivity in area 17 of binocularly deprived cats.

Eight cats were binocularly deprived of pattern vision by rearing in masks from the time of eye opening. Twenty five groups of 3 neurons and 28 neuronal pairs were studied in visual orientation columns of their striate cortices. The crosscorrelograms of neuronal discharges were analyzed and the inference of underlying interneuronal connectivity was made. The results were compared with the normal cats data obtained earlier in an identical experiment. Total number of existing interactions was only slightly reduced: from 95010 of analyzed pairs in normal cats to 90 percent in deprived animals. The most pronounced effect of visual deprivation was the reduction of the percentage of neuronal pairs that shared the same source of input from 61 to 34 percent. The proportion of direct excitatory connections was not affected, while an increase in the number of inhibitory correlations was found.

Animals↗
PubMedDate not supplied

Modelling the formation of working memory with networks of integrate-and-fire neurons connected by plastic synapses.

In this paper we review a series of works concerning models of spiking neurons interacting via spike-driven, plastic, Hebbian synapses, meant to implement stimulus driven, unsupervised formation of working memory (WM) states. Starting from a summary of the experimental evidence emerging from delayed matching to sample (DMS) experiments, we briefly review the attractor picture proposed to underlie WM states. We then describe a general framework for a theoretical approach to learning with synapses subject to realistic constraints and outline some general requirements to be met by a mechanism of Hebbian synaptic structuring. We argue that a stochastic selection of the synapses to be updated allows for optimal memory storage, even if the number of stable synaptic states is reduced to the extreme (bistable synapses). A description follows of models of spike-driven synapses that implement the stochastic selection by exploiting the high irregularity in the pre- and post-synaptic activity. Reasons are listed why dynamic learning, that is the process by which the synaptic structure develops under the only guidance of neural activities, driven in turn by stimuli, is hard to accomplish. We provide a 'feasibility proof' of dynamic formation of WM states in this context the beneficial role of short-term depression (STD) is illustrated. by showing how an initially unstructured network autonomously develops a synaptic structure supporting simultaneously stable spontaneous and WM states in this context the beneficial role of short-term depression (STD) is illustrated. After summarizing heuristic indications emerging from the study performed, we conclude by briefly discussing open problems and critical issues still to be clarified.

Action Potentials↗
PubMed1997

Oscillatory mechanisms in pairs of neurons connected with fast inhibitory synapses.

We study dynamical mechanisms underlying oscillatory behavior in reciprocal inhibitory pairs of neurons, using a two-dimensional cell model. We introduce one-and-two dimensional phase portraits to illustrate the behaviors, thus reducing the study of dynamical mechanisms to planar geometrical properties. We examined whether other mechanisms besides the escape and release mechanisms (Wang and Rinzel, 1992) might be needed for some cases of reciprocal inhibition, and show that, within the confines of a simple two-dimensional cell model, escape and release are sufficient for all cases. We divided the behaviors of a single cell into six different types and examined the joint behaviors arising from every combination of pairs of cells with behaviors drawn from these six types. For the case of two quiescent cells or two cells each having plateau potentials, bifurcation diagrams demonstrate the relations between synaptic threshold and synaptic strength necessary for oscillations by escape, oscillations by release, or network-generated plateau potentials. Thus we clarify the relationship between plateau potentials and oscillations in a cell. Using the two dimensional cell model we examine 1:N beating between cells and find that our simple model displays many of the essential dynamical properties displayed by more sophisticated models, some of which relate to thalamocortical spindling.

Neural Networks, Computer↗
PubMed2001

Improved data processing for optical imaging of developing neuronal connectivity in the neonatal mouse barrel cortex.

Optical recording methods using voltage-sensitive dyes have proven valuable for the analysis of neuronal networks both in vivo and in vitro. This technique detects membrane potential changes as changes in the absorption or fluorescence of voltage-sensitive dyes incorporated into the cellular plasma membranes. The reliability of the optical recording technique is dependent on the dye-related response being fast enough to follow the electrical activity and of the response being more or less proportional to the amplitude of the membrane potential change. A high spatial resolution can be achieved using an appropriate imaging system and a dye with a response of sufficiently high signal-to-noise ratio. Thus, it is now anticipated that this method will be able to shed more light on the spatio-temporal information processing of neocortical circuitry. While the FUJIX HR Deltaron 1700 optical imaging system offers a reasonably high time (0.6 ms) and space-resolution (7 microm at 10x magnification), one drawback of this system, however, is its relatively poor data processing capabilities. We have therefore developed a protocol to improve the signal-to-noise ratio by modifying the calculation algorithm of the optical data. Consequently, we characterized optical responses in thalamocortical slices to find developmental landmarks of thalamocortical and intracortical connectivity in the neonatal mouse barrel cortex. Successful application of this method has been published on the analysis of thalamocortical glutamatergic connectivity [8].

Algorithms↗
PubMed1999

Neuronal connections through the posterior commissure in the frog Rana esculenta.

The cobalt-labelling technique was used. After iontophoretic injections of cobaltic-lysine complex into the posterior commissure, fibres and neurons were bilaterally labelled in the posterior thalamic nucleus, three other pretectal nuclei, the optic tectum, the nucleus of the medial longitudinal fasciculus, and in the basal optic nucleus. Unilateral cobalt injections into the terminal areas of the posterior commissure in the mesencephalic tegmentum, labelled neurons in the above-mentioned nuclei ipsilaterally, and some cells contralaterally. The connections through the frog's posterior commissure are very similar to those in mammals.

Animals↗
PubMed2001

Lateral magnocellular nucleus of the anterior neostriatum (LMAN) in the zebra finch: neuronal connectivity and the emergence of sex differences in cell morphology.

The song system of birds provides a model system to study basic mechanisms of neuronal plasticity and development underlying learned behavior. Song learning and production involve discrete sets of interconnected nuclei in the avian brain. One of these nuclei, the lateral magnocellular nucleus of the anterior neostriatum (LMAN), is the output of the so-called anterior forebrain pathway known to be essential for learning and maintenance of song, both processes depending on auditory feedback. In zebra finches, only males sing and this sexually dimorphic behavior is mirrored by sexual dimorphism in neuronal structure that develops during ontogeny. Female zebra finches are not able to sing and nuclei of the song system are strongly reduced in size or even lacking, when compared to male brains. Only LMAN can be delineated as easily in females as in males. Since female zebra finches, despite being unable to sing, recognize song just as males do and form a memory for song (model acquisition) early in life, LMAN is a putative candidate for song acquisition in both sexes. Therefore, development of LMAN was studied at the cellular and ultrastructural level in both male and female zebra finches. Regressive development of dendritic spines, enlargement of neuronal cell body and nuclei size, as well as changes at the nucleolar level are events all occurring exclusively in males, when song learning progresses. The decline in synapse number and the augmentation in synaptic contact length at synapses in LMAN in males are indicative for synaptic plasticity, whereas in females synapse number and synaptic contact length remain unchanged.

Animals↗
PubMed1998

[Analysis of neuronal connections in the basal ganglia].

Morphological features indicating occurrence of two types of extrasynaptic chemical transmission were observed within rat basal ganglia. (1) Striatonigral neurons containing substance P (SP) sent many axon collaterals equipped with axonal varicosities to the striatum: the varicosities displayed synaptophysin-like immunoreactivity (-LI). However, only 15% of the varicosities appeared to be in close contact with structures showing SP receptor (SPR)-LI. Many of axon terminals of striatonigral neurons were confirmed electron microscopically not to be in synaptic contact with SPR-like immunoreactive structures within the striatum. SP released from the varicosities might, at least partly, diffuse to reach SPR at distance from the release sites. (2) Immunoreactivities for metabotropic glutamate receptors (mGluRs) 4 a, 7 a, 7 b and 8 were in axon terminals within the globus pallidus (external segment of the globus pallidus in primates). The immunoreactivities disappeared after destruction of the striatum, but not after destruction of the subthalamic nucleus. The immunoreactivity for mGluR 7 a was confirmed electron microscopically to be within axon terminals showing glutamic acid decarboxylase-LI. Glutamate released from glutamatergic subthalamopallidal neurons might partly spilled over from the synaptic sites to reach mGluRs on "nearby" axon terminals of GABAergic striatopallidal neurons. Functional significance of thalamostriatal and corticosubthalamic fibers was also discussed.

Animals↗
PubMedDate not supplied

[Cross-correlational analysis of the neuronal connections of the cerebellum in the waking rabbit].

The methods of cross-interval and crosscorrelation analysis were used to study interneuronal connections in cerebellar vermis in awake rabbit. Crosscorrelation, or spike-triggering method, complemented the analysis of cross-intervals which estimated the neuronal interaction comparing spike sequences as point processes. Among 16 neuronal pairs recorded intra- or extracellularly 10 pairs were considered as interconnected. Inhibitory interconnections dominated. The inhibitory neuronal interconnections were revealed in pairs with complex spikes. Neurons which constituted pairs with reciprocal excitatory-inhibitory interaction fired only simple spikes. The variability and plasticity of common inputs to Purkinje cells were seemingly lower than those of direct connections which probably transmitted the output signals of Purkinje cells.

Action Potentials↗