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PubMed1997

[Visually-induced gamma band responses in human EEG- expression of cortical stimulus representation?].

The features of a visual stimulus are processed in different regions of the visual cortex with no direct axonal connections. Therefore, neurons in the distributed processing areas must be connected in some way to form the physiological substrate of the percept. On the basis of theoretical considerations and animal experiments, it has been proposed that synchronization of neuronal oscillatory firing patterns in the gamma band range (above 30 Hz) might be essential in linking the anatomically distant cell assemblies that represent the various features of the stimulus. The present work reports on three experiments in which the functional relevance of induced gamma band responses were investigated in the human EEG. Using an identical stimulation design, as used in animal studies, it was demonstrated that human induced gamma band responses resembled those reported from intracortical recordings from animals. It was further shown that alpha and gamma band activities differed in temporal characteristics as well as in topographical features, indicating the representation of different cortical functional states. In accordance with previous animal and human experimental findings, a complex moving stimulus was related to a suppression of induced gamma band activity as opposed to a standing complex stimulus.

Animals↗
PubMed2004

Increased excitatory synaptic activity and local connectivity of hippocampal CA1 pyramidal cells in rats with kainate-induced epilepsy.

Formation of local excitatory circuits may contribute to epileptogenesis. We tested the hypothesis that epileptogenesis is associated with increased recurrent excitation in the hippocampal CA1 area of rats with kainate-induced epilepsy. Whole cell recordings were obtained during focal flash photolysis of caged glutamate, which served as a focal excitant to activate local pyramidal cells and to study possible connections between neurons. Kainate-treated rats with spontaneous seizures were studied months after status epilepticus and were compared with saline-injected control rats. Experiments were done in isolated CA1 minislices and in bicuculline to block GABA(A) receptors. Spontaneous excitatory postsynaptic currents (sEPSCs) were present in 42% of the CA1 pyramidal cells from controls and 62% from kainate-treated rats. The frequency of sEPSCs in the kainate group was significantly higher than that in the control group, but mean amplitude was not different. Flash photolysis of caged glutamate on the somatodendritic area of CA1 pyramidal neurons caused a burst of action potentials. Local excitatory connections between CA1 pyramidal cells were found in 4 of 48 neurons (8%) in slices from control animals, but in significantly more neurons (12 of 37; 32%) from rats with kainate-induced epilepsy exhibited interconnections (P < 0.001). Photoactivation of glutamate on recorded CA1 pyramidal cells in the kainate group sometimes caused afterdischarges, but not in controls. The kainate-treated rats with pyramidal cells that responded to photostimulaltion with repetitive EPSCs appeared to have experienced more severe seizures. These data provide new electrophysiological evidence for the formation of recurrent excitatory circuits in the CA1 area of rats with kainate-induced epilepsy.

Animals↗
PubMed2005

Topographical maps as complex networks.

The neuronal networks in the mammalian cortex are characterized by the coexistence of hierarchy, modularity, short and long range interactions, spatial correlations, and topographical connections. Particularly interesting, the latter type of organization implies special demands on developing systems in order to achieve precise maps preserving spatial adjacencies, even at the expense of isometry. Although the object of intensive biological research, the elucidation of the main anatomic-functional purposes of the ubiquitous topographical connections in the mammalian brain remains an elusive issue. The present work reports on how recent results from complex network formalism can be used to quantify and model the effect of topographical connections between neuronal cells over the connectivity of the network. While the topographical mapping between two cortical modules is achieved by connecting nearest cells from each module, four kinds of network models are adopted for implementing intramodular connections, including random, preferential-attachment, short-range, and long-range networks. It is shown that, though spatially uniform and simple, topographical connections between modules can lead to major changes in the network properties in some specific cases, depending on intramodular connections schemes, fostering more effective intercommunication between the involved neuronal cells and modules. The possible implications of such effects on cortical operation are discussed.

Animals↗
PubMed1990

The formation of cooperative cell assemblies in the visual cortex.

During a critical period of postnatal development of the mammalian visual cortex, synaptic connections are susceptible to use-dependent modifications. Synaptic connections strengthen if pre- and postsynaptic elements are active simultaneously and postsynaptic depolarization is sufficient to allow for the activation of N-methyl-D-aspartate (NMDA)-receptor-gated conductances. By contrast, synaptic gain decreases if postsynaptic activation exceeds a critical threshold and presynaptic afferents are not capable of activating NMDA-receptor-dependent conductances. These processes lead to selective stabilization of connections between neuronal elements which often exhibit correlated activity and thus modify connectivity according to functional criteria. It is suggested that such experience-dependent selection of circuits serves different purposes at different levels of visual processing. At the input stage to the striate cortex it contributes to optimize the match between the representations of the two eyes. At a later stage of processing it participates in the development of selective connections between cortical columns and thereby serves to establish neuronal representations for frequently occurring constellations of features. Use-dependent changes of synaptic gain can also be induced in the mature visual cortex. These modifications follow the same rules as those occurring during early development and appear to depend on similar molecular mechanisms. However, in the adult the changes of synaptic gain do not seem to be followed by major rearrangements of connectivity. This suggests developmental alterations in mechanisms responsible for growth, removal and stabilization of synaptic connections. Actually, many of the cellular mechanisms thought to be involved in use-dependent synaptic plasticity change during development but it is still unclear which of them are responsible for the definitive stabilization of functionally confirmed pathways.

Aging↗
PubMed1989

Control of phrenic nerve activity and blood pressure by the medullary raphe nuclei in cats.

Electrical and chemical stimulation methods were used to determine the topographic organization of the medullary raphe nuclei (MRN) in controlling the systemic arterial blood pressure (BP) and phrenic nerve activities (PNA). Decerebrated, unanesthetized and bilateral vagotomized cats were used. Effective points in the MRN were systematically explored with constant current stimulation. We found stimulation of the rostral MRN produced a decrease in PNA amplitude and increase in BP and PNA frequency. Stimulation of the caudal MRN produced increases in BP and the amplitude and frequency of PNA. Microinjection of glutamate solution into the caudal or the rostral MRN points produced qualitatively similar results. Thus, we concluded that the caudal MRN neurons had excitatory connections whereas the rostral MRN neurons had excitatory and inhibitory connections to the cardiovascular preganglionic neurons and the phrenic nerve motoneurons.

Animals↗
PubMed1979

Pathways and polarities of synaptic interactions in the inner retina of the mudpuppy: II. Insight revealed by an analysis of latency and threshold.

Intracellular recording experiments in the mudpuppy (Necturus maculosus) have demonstrated that depolarizing bipolars show a one-half to one log unit higher threshold to light stimuli and a longer latency when compared to hyperpolarizing bipolars. This threshold difference cannot be ascribed to differences in rod and cone connections. Experimentally it was possible to use these differences to evaluate postbipolar cell connections; such experiments support the idea that some neurons are connected to one or the other bipolar cell type, while on-off cells receive input from both.

Animals↗
PubMed2001

Synaptic depression mediates bistability in neuronal networks with recurrent inhibitory connectivity.

When depressing synapses are embedded in a circuit composed of a pacemaker neuron and a neuron with no autorhythmic properties, the network can show two modes of oscillation. In one mode the synapses are mostly depressed, and the oscillations are dominated by the properties of the oscillating neuron. In the other mode, the synapses recover from depression, and the oscillations are primarily controlled by the synapses. We demonstrate the two modes of oscillation in a hybrid circuit consisting of a biological pacemaker and a model neuron, reciprocally coupled via model depressing synapses. We show that across a wide range of parameter values this network shows robust bistability of the oscillation mode and that it is possible to switch the network from one mode to the other by injection of a brief current pulse in either neuron. The underlying mechanism for bistability may be present in many types of circuits with reciprocal connections and synaptic depression.

Animals↗
PubMed2005

Synchronized firings in the networks of class 1 excitable neurons with excitatory and inhibitory connections and their dependences on the forms of interactions.

Synchronized firings in the networks of class 1 excitable neurons with excitatory and inhibitory connections are investigated, and their dependences on the forms of interactions are analyzed. As the forms of interactions, we treat the double exponential coupling and the interactions derived from it: pulse coupling, exponential coupling, and alpha coupling. It is found that the bifurcation structure of the networks depends mainly on the decay time of the synaptic interaction and the effect of the rise time is smaller than that of the decay time.

Action Potentials↗
PubMed1989

Axons containing neuropeptide Y innervate arginine vasopressin-containing neurons in the rat paraventricular nucleus. Dual electron microscopic immunolabeling.

Synaptic connections between neurons immunoreactive for arginine vasopressin (AVP) and axon terminals immunoreactive for neuropeptide Y (NPY) were found in the magnocellular part of the paraventricular nucleus (PVN) in the rat hypothalamus. In pre-embedding double immunolabeling, NPY axon terminals labeled with diaminobenzidine (DAB) reaction product established synaptic junctions on the perikarya and neuronal processes of AVP neurons labeled with silver-gold particles. Ultrastructural morphology of the neurons was more suitably preserved by a combination of pre- and post-embedding procedures. The presynaptic NPY terminals contained many small clear vesicles and a few cored vesicles, and DAB chromogen (immunoreaction product) was located on the surface of the vesicular profiles and on the core. The postsynaptic AVP neurons possessed many large secretory granules labeled with gold particles. At the synaptic junctions, small clear vesicles were accumulated at the presynaptic membrane, and the postsynaptic membrane was coated with a dense accumulation of fine electron dense particles. The perikarya also received synapses made by immuno-negative axon terminals containing many small clear vesicles and a few cored vesicles. These terminals were found more frequently than those containing NPY.

Animals↗
PubMed1989

Neuronal loss and neuronal atrophy. Computer simulation in connection with Alzheimer's disease.

A decrease in the number of neuronal profiles in the isocortex of man may be observed on microscopic sections in aging and in degenerative diseases such as Alzheimer's disease. It can be the consequence of a loss of neurons per unit volume or of a reduction of the neuronal volume (i.e. pseudo-loss). This latter possibility has been tested by simulating neuronal atrophy, with sections of various thicknesses. An unfolding algorithm was used for the simulation. The data published in the current literature concerning Alzheimer's disease were treated with the unfolding algorithm. The neocortical pseudo-loss did not exceed a few percentage points, probably much less than the measurement error. New methods of cell counting have been recently proposed to discriminate real from pseudo-loss. They should be used when the risk of dealing with pseudo-loss is high. A chart to assess the percentage of pseudo-loss as a function of perikaryal atrophy is proposed: it relies on the evaluation of the size of the cell relative to the section thickness (relative caliper diameter). This chart may be used to correct cell counts of homogeneous cell populations.

Adult↗
PubMed1994

Age-related effects of triphenyl phosphite-induced delayed neuropathy on central visual pathways in the European ferret (Mustela putorius furo).

The objective of this study was to investigate the relationship between the maturation of visual system neurons and the onset of their susceptibility to triphenyl phosphite (TPP)-induced delayed neurotoxicity in the European ferret. We administered single subcutaneous doses of TPP (1184 mg/kg body wt) to 1- to 10-week-old ferret kits to assess the effects on connections and neurons of the developing lateral geniculate thalamic nucleus (LGN) and primary visual cortex. Brains were processed with a modified Fink-Heimer silver-impregnation method. Axonal and terminal degeneration were first noted in the LGN of kits injected at 5 weeks of age. The severity of the degeneration increased in kits injected at later ages and reached adult densities and configurations in ferrets injected at 10 weeks of age. Degenerating neuronal cell bodies were also present in the LGN of kits injected at 7 weeks of age and older. In the visual cortex, axonal and terminal degeneration were consistently present in kits injected at 8 weeks of age and attained adult-like densities in kits injected at 10 weeks of age. Previous studies have reported that the ferret visual system appears to reach anatomical maturity (as defined by mature LGN lamination patterns, the location and density of axon terminals originating from neurons in the retina and LGN, and the migration and synaptic connections of cortical neurons) by 4-5 weeks of age. A temporal comparison of these normal developmental data with the degeneration data obtained in the present study suggests that immature neurons in the visual system of the ferret are not susceptible to TPP-induced delayed neurotoxicity but only become so after they have achieved some degree of maturity. Whether the LGN neurons undergoing degeneration are directly affected by TPP or are showing a transneuronal response to loss of afferent input remains unresolved.

Age Factors↗
PubMedDate not supplied

[The pharmacological testing of intracortical interneuronal connections].

An attempt is made to study the influence of acetylcholine on functional connections of cortical neurons and their frequency characteristics. Multiunit activity was recorded in the sensorimotor cortex of immobilized and freely moving rats. Crosscorrelation analysis was used. Influence of acetylcholine (Ach) and Ca chelator ethyleneglicoltetraacetat (EGTA) on the functional characteristics of the neighbouring neurons was studied in the first series of experiments. The substances were iontophoretically applied to the sensorimotor cortex neurons of the immobilized unanesthetized rats. Application of Ach led to variation in the frequency characteristics of single neurons and in the majority cases did not affect the neuronal interrelations. EGTA application, independently on the background frequency of the neuronal activity, resulted in disappearance of interneuronal connections which recovered after the end of EGTA effect. The second series of experiments was carried out in freely moving rats. System injection of galantamine essentially increased the frequency of activity of the cortical neurons not affecting their network activity. We suppose that intracortical relations can be realized independently on the extracortical influences which are manifested in variations in the background impulsation of the single neurons. Qualitative estimation of Ach influence on the functional characteristics of the cortical neurons do not reveal Ach effects on formation of intracortical connections. The technique used by us may be applied in further studies of intracortical neurons connections.

Acetylcholine↗
PubMed1982

[Study of the connections of brain stem respiratory nuclei by the technic of retrograde transport of horseradish peroxidase].

The method of horseradish peroxidase retrograde axonal transport was used to study the connections between neurons of respiratory nuclei and reticular formation of medulla oblongata and descending fibre pathways from these structures in the spinal cord of cats. It is shown that neurons of the nucleus ambiguus and nucleus retroambiguus (the ventral respiratory group) are connected with the ventrolateral part of nucleus tractus solitarius (the dorsal respiratory group) and from direct bilateral connections with each other and with the medial part of medulla oblongata. A wide developed system of direct connections is revealed between the neurons of respiratory nuclei of both parts of the brain stem. A possible role of the studied nuclei is discussed for the rhythmogenesis of breathing and regulation of the respiratory and other motor functions.

Animals↗
PubMed1994

A measure for brain complexity: relating functional segregation and integration in the nervous system.

In brains of higher vertebrates, the functional segregation of local areas that differ in their anatomy and physiology contrasts sharply with their global integration during perception and behavior. In this paper, we introduce a measure, called neural complexity (CN), that captures the interplay between these two fundamental aspects of brain organization. We express functional segregation within a neural system in terms of the relative statistical independence of small subsets of the system and functional integration in terms of significant deviations from independence of large subsets. CN is then obtained from estimates of the average deviation from statistical independence for subsets of increasing size. CN is shown to be high when functional segregation coexists with integration and to be low when the components of a system are either completely independent (segregated) or completely dependent (integrated). We apply this complexity measure in computer simulations of cortical areas to examine how some basic principles of neuroanatomical organization constrain brain dynamics. We show that the connectivity patterns of the cerebral cortex, such as a high density of connections, strong local connectivity organizing cells into neuronal groups, patchiness in the connectivity among neuronal groups, and prevalent reciprocal connections, are associated with high values of CN. The approach outlined here may prove useful in analyzing complexity in other biological domains such as gene regulation and embryogenesis.

Animals↗
PubMed2004

Epilepsy in small-world networks.

In hippocampal slice models of epilepsy, two behaviors are seen: short bursts of electrical activity lasting 100 msec and seizure-like electrical activity lasting seconds. The bursts originate from the CA3 region, where there is a high degree of recurrent excitatory connections. Seizures originate from the CA1, where there are fewer recurrent connections. In attempting to explain this behavior, we simulated model networks of excitatory neurons using several types of model neurons. The model neurons were connected in a ring containing predominantly local connections and some long-distance random connections, resulting in a small-world network connectivity pattern. By changing parameters such as the synaptic strengths, number of synapses per neuron, proportion of local versus long-distance connections, we induced "normal," "seizing," and "bursting" behaviors. Based on these simulations, we made a simple mathematical description of these networks under well-defined assumptions. This mathematical description explains how specific changes in the topology or synaptic strength in the model cause transitions from normal to seizing and then to bursting. These behaviors appear to be general properties of excitatory networks.

Cell Communication↗
PubMed1999

Formation of functional synaptic connections between cultured cortical neurons from agrin-deficient mice.

Numerous studies suggest that the extracellular matrix protein agrin directs the formation of the postsynaptic apparatus at the neuromuscular junction (NMJ). Strong support for this hypothesis comes from the observation that the high density of acetylcholine receptors (AChR) normally present at the neuromuscular junction fails to form in muscle of embryonic agrin mutant mice. Agrin is expressed by many populations of neurons in the central nervous system (CNS), suggesting that this molecule may also play a role in neuron-neuron synapse formation. To test this hypothesis, we examined synapse formation between cultured cortical neurons isolated from agrin-deficient mouse embryos. Our data show that glutamate receptors accumulate at synaptic sites on agrin-deficient neurons. Moreover, electrophysiological analysis demonstrates that functional glutamatergic and gamma-aminobutyric acid (GABA)ergic synapses form between mutant neurons. The frequency and amplitude of miniature postsynaptic glutamatergic and GABAergic currents are similar in mutant and age-matched wild-type neurons during the first 3 weeks in culture. These results demonstrate that neuron-specific agrin is not required for formation and early development of functional synaptic contacts between CNS neurons, and suggest that mechanisms of interneuronal synaptogenesis are distinct from those regulating synapse formation at the neuromuscular junction.

2-Amino-5-phosphonovalerate↗
PubMed1985

The morphology and synaptic connections of spiny stellate neurons in monkey visual cortex (area 17): a Golgi-electron microscopic study.

Based on a gold-toning, Golgi-electron microscope examination of 12 small and medium-sized spiny stellate neurons in laminae 4A, 4B, and 4C of the monkey visual cortex (area 17), the ultrastructure of the cell somata, dendrites, and axons of these neurons is described. Particular attention is paid to the synapses involving the surface of different parts of these neurons. Only symmetric synapses occur on the somata of spiny stellate neurons, and these occur with a frequency of 11.0-15.9 synapses/100 microns2 perikaryal surface. Symmetric synapses also occur on dendritic shafts and, occasionally, on dendritic spines. Asymmetric synapses are occasionally present along the dendritic shafts of spiny stellate neurons, but the majority of asymmetric synapses (75-95%) occur on their dendritic spines. The initial axon segments of the smallest spiny stellate neurons possess no axo-axonal synapses, but several symmetric synapses are present along the initial segment of a medium-sized, spiny stellate neuron in layer 4B. Fifty-three synapses made by boutons of the axons of these spiny stellate neurons have been identified, and all are asymmetric. Sixty per cent of the synapses are formed by boutons en passant and the remainder by the terminal swellings of spine-like axonal appendages, boutons terminaux. Of the synapses formed by the axons of spiny stellate cells, axo-spinous synapses outnumber axo-dendritic synapses two to one, and axo-dendritic synapses involve both spinous and aspinous dendrites. Evidence is presented which suggests that many of the axon terminals forming asymmetric synapses with the dendritic shafts and spines of spiny stellate neurons are derived from other spiny stellate neurons.

Animals↗
PubMed1987

Morphology and synaptic connections of crossed corticostriatal neurons in the rat.

The neurons of origin of the bilateral corticostriatal projection arising from the medial agranular cortical field in rats were identified by antidromic activation from contralateral neostriatal stimulation. The same cells were tested for antidromic activation from the contralateral neocortex and for orthodromic responses to stimulation of neocortex of the contralateral hemisphere or ipsilateral rostral thalamus. The neurons were then stained by intracellular injection of horseradish peroxidase. The laminar distribution of these neurons was compared to that of cortical cells stained retrogradely after injection of wheat germ agglutinin/HRP in the ipsilateral or contralateral neostriatum. The morphological features of physiologically identified corticostriatal neurons, their laminar organization, and their responses to stimulation were examined and compared with crossed corticocortical and brainstem-projecting cells. Crossed corticostriatal cells of the medial agranular cortical field were medium-sized pyramidal neurons found in the superficial part of layer V and in the deep part of layer III. Their basilar dendritic fields and initial intracortical axon collateral arborizations were coextensive with the layer defined by the distribution of corticostriatal neurons. The apical dendrites were thin and sparsely branched but consistently reached layer I, where they made a small arborization. These morphological features were shared by cortical neurons projecting to contralateral neocortex but not responding antidromically to stimulation of contralateral neostriatum, but they were not shared by brainstem-projecting cortical cells. Orthodromic responses to contralateral cortical stimulation consisted of brief excitatory postsynaptic potentials that were followed by powerful and longer-lasting inhibitory postsynaptic potentials. Corticostriatal cells also exhibited small excitatory postsynaptic potentials in response to thalamic stimulation. Many crossed corticostriatal neurons were also commissural corticocortical neurons. The results of reciprocal collision tests showed that this was due to the existence of two separate axonal branches, one projecting to contralateral neocortex and one to contralateral neostriatum. Intracellular staining of these neurons revealed ipsilateral axonal projections to the neostriatum and cortex.

Animals↗