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PubMed2005

Simulation of the neuronal interactions and connection of neuronal activity with changes of heart rhythm and myocardial electrophysiological properties.

The purpose was to create the software for analysis of temporal relationship between spike trains of several neurons and connection of neuronal activity with changes of heart rhythm and some electrocardiogram parameters. The designed software represents an integrated estimation of the cross-correlograms and cardiac-cycle triggered correlograms combination. It permits the study of the nonrandom temporal relationship between spike trains of neurons using experimental data and the estimation of the roles of one neuron and a group of them and the role of their discharges patterns in changes of heart rhythm and electrophysiological properties of the myocardium.

Action Potentials↗
PubMed2003

Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia.

The molecular and cellular origin of the primary neurons of the inner ear, the vestibular and spiral neurons, is reviewed including how they connect to the specific sensory epithelia and what the molecular nature of their survival is. Primary neurons of the ear depend on a single basic Helix-Loop-Helix (bHLH) protein for their formation, neurogenin 1 (ngn1). An immediate downstream gene is the bHLH gene neuronal differentiation (NeuroD). Targeted null mutations of ngn1 results in absence of primary neuron formation; targeted null mutation of NeuroD results in loss of almost all spiral and many vestibular neurons. NeuroD and a later expressed gene, Brn3a, play a role in pathfinding to and within sensory epithelia. The molecular nature of this pathfinding property is unknown. Reduction of hair cells in ngn1 null mutations suggests a clonal relationship with primary neurons. This relationship may play some role in specifying the identity of hair cells and the primary neurons that connect with them. Primary neuron neurites growth to sensory epithelia is initially independent of trophic factors released from developing sensory epithelia, but becomes rapidly dependent on those factors. Null mutations of specific neurotrophic factors lose distinct primary neuron populations which undergo rapid embryonic cell death.

Animals↗
PubMed2003

Neurogenin2 specifies the connectivity of thalamic neurons by controlling axon responsiveness to intermediate target cues.

Many lines of evidence indicate that important traits of neuronal phenotype, such as cell body position and neurotransmitter expression, are specified through complex interactions between extrinsic and intrinsic genetic determinants. However, the molecular mechanisms specifying neuronal connectivity are less well understood at the transcriptional level. Here we demonstrate that the bHLH transcription factor Neurogenin2 cell autonomously specifies the projection of thalamic neurons to frontal cortical areas. Unexpectedly, Ngn2 determines the projection of thalamic neurons to specific cortical domains by specifying the responsiveness of their axons to cues encountered in an intermediate target, the ventral telencephalon. Our results thus demonstrate that in parallel to their well-documented proneural function, bHLH transcription factors also contribute to the specification of neuronal connectivity in the mammalian brain.

Animals↗
PubMed2005

Retinoic acid induction of ES-cell-derived neurons: the radial glia connection.

Neuronal induction by retinoic acid (RA) is commonly used in embryonic stem (ES) cell differentiation. Two recent papers show that this paradigm induces a population of neurogenic precursors with properties of radial glia. Upon differentiation, RA-treated cells give rise to a defined and developmentally restricted neuronal lineage. This role of RA in cell fate specification provides new perspectives for studying the radial glia-neuron transition and for generating homogenous populations of neurons from ES cells.

Animals↗
PubMed2005

Efferent and afferent connections of GABAergic neurons in the supratrigeminal and the intertrigeminal regions. An immunohistochemical tract-tracing study in the GAD67-GFP knock-in mouse.

It has been reported in the cat and rat that inhibitory premotor neurons, which send their axons to motoneurons of the trigeminal motor nucleus (Vm) are distributed in the reticular regions around the Vm, especially in the supratrigeminal region (Vsup) and the intertrigeminal region (Vint). In the present study, we examined neuronal connections of GABAergic neurons in the Vsup and Vint in the mouse by utilizing the adult heterozygous GAD67-GFP knock-in mouse, in which green fluorescence protein (GFP) is expressed in GABAergic neurons under the control of the endogenous GAD (GAD67) gene promoter [Yanagawa, Y., Kaneko, K., Kanbara, N., Totsuka, M., Yagi, T., Obata, K., 2001. Development of mouse expressing GFP in GABAergic neurons. Neurosci. Res. Suppl. 25, S77; Tamamaki, N., Yanagawa, Y., Tomioka, R., Miyazaki, J.-I., Obata, K., Kaneko, T., 2003. Green fluorescent protein expression and colocalization with calretinin, parvalbumin and somatostatin in the GAD67-GFP knock-in mouse. J. Comp. Neurol. 467, 60-79]. The connections were examined light- and electron-microscopically by combining the anterograde or the retrograde tract-tracing method with the immunohistochemical method for GFP. The data indicated that the Vsup and Vint of the mouse contained GABAergic neurons, which received projection fibers from the marginal layer of the nucleus of the spinal tract of the trigeminal nerve (Vc) on the ipsilateral side and sent their axons to the Vm on the contralateral side. Some of these GABAergic neurons may represent Vm-premotor neurons that receive nociceptive input from the Vc to elicit jaw-opening reflex by inhibiting jaw-closing Vm-motoneurons.

Animals↗
PubMed1981

Intraanalyzer conditioned reflex properties of two-way connections of cortical neurons in cats.

One of the principles in the formation of integrating activity of the brain appears to be a two-way character of neuronal connections. Forward and backward conditioned connections demonstrate the acquired properties of two-way relations in the cerebral cortex. Interneuronal cortical connections and their modification in conditioned reflex activity were studied in a alert cats with chronically implanted electrodes using a statistical method for analysis of two impulse flows. Multineuronal activity was recorded in the auditory cortex. All of the investigated neurons were divided into pairs according to their functional relations: (1) with two-way connections, (2) with one-way connections and (3) completely independent pairs. The functional interrelation in the cortical microarea, and between cortical microareas, were defined according to the space distribution of neuronal pairs. Elaboration of the motor conditioned reflex led to an intensification of two-way connections both in the cortical microarea and between remote neurons. Extinction of the conditioned reflex exerted almost no effect on the intensity of two-way connections, but considerably decreased the number of independent neuronal pairs at the expense of reduction in the number of one-way connections between cortical microareas. Thus, acquisition and extinction of the conditioned reflex were accompanied by intensive interconnected neuronal activity. The features of interneuronal connection properties during extinction inhibition were the attenuation of successive information transfer in cortical cells, which prevented the impulse activity from passing to effector pathways.

Animals↗
PubMedDate not supplied

[Neuronal activity during formation of reverse conditioned connections].

Neuronal characteristics of backward conditioned connections were studied in alert cats in chronic experiments on the model of alimentary conditioned reflex, elaborated in response to electrical stimulation of the brain visual structures (LGB or optic tract). The patterns of neuronal activity in the visual cortex (projection of the conditioned stimulus) were similar both in response to the conditioned stimulus (its isolated presentation) and in tests of the activation of backward conditioned connections (isolated presentation of milk, intersignal licking movements, with stable conditioned reflex). A dependence was revealed of the reactivity of visual neurones during activation of backward conditioned connections on their afferent properties.

Animals↗
PubMed2004

Maps in the brain: what can we learn from them?

In mammalian visual cortex, neurons are organized according to their functional properties into multiple maps such as retinotopic, ocular dominance, orientation preference, direction of motion, and others. What determines the organization of cortical maps? We argue that cortical maps reflect neuronal connectivity in intracortical circuits. Because connecting distant neurons requires costly wiring (i.e., axons and dendrites), there is an evolutionary pressure to place connected neurons as close to each other as possible. Then, cortical maps may be viewed as solutions that minimize wiring cost for given intracortical connectivity. These solutions can help us in inferring intracortical connectivity and, ultimately, in understanding the function of the visual system.

Animals↗
PubMed2000

Predominant information transfer from layer III pyramidal neurons to corticospinal neurons.

Connections of layer III pyramidal neurons to corticospinal neurons of layer V and corticothalamic neurons of layer VI in the rat primary motor cortex were examined in brain slices by combining intracellular staining with Golgi-like retrograde labeling of corticofugal neurons. Forty layer III pyramidal neurons stained intracellularly were of the regular-spiking type, showed immunoreactivity for glutaminase, and emitted axon collaterals arborizing locally in layers II/III and/or V. Nine of them were reconstructed for morphologic analysis; 15.2% or 3.8% of varicosities of axon collaterals of the reconstructed neurons were apposed to dendrites of corticospinal or corticothalamic neurons, respectively. By confocal laser scanning and electron microscopy, some of these appositions were revealed to make synapses. These findings suggest that corticospinal neurons receive information from the superficial cortical layers four times more frequently than corticothalamic neurons. The connections were further examined by intracellular recording of excitatory postsynaptic potential (EPSP) that were evoked in layer V and layer VI pyramidal neurons by stimulation of layer II/III. EPSPs evoked in layer V pyramidal neurons showed short and constant onset latencies, suggesting their monosynaptic nature. In contrast, most EPSPs evoked in layer VI pyramidal neurons had long onset latencies, showed double-shock facilitation of onset latency, and were largely suppressed by an N-methyl-D-aspartic acid receptor blocker, suggesting that they were polysynaptic. The results suggest that information from the superficial cortical layers is transferred directly and efficiently to corticospinal neurons in layer V and thereby exerts an important influence on cortical motor output. Corticothalamic neurons are, in contrast, considered relatively independent of, or indirectly related to, information processing of the superficial cortical layers.

Animals↗
PubMed1981

Selection of a novel connection by adult molluscan neurons.

Predictable change in neuronal connectivity can be induced in the buccal ganglia of adult Helisoma snails when neuritic growth is evoked by axotomy. Both transient and stable novel electrical connections are established between identified neurons. The breaking of inappropriate, normally transient connections is contingent on the formation of an appropriate connection.

Animals↗
PubMed1994

Information processing within the motor cortex. II. Intracortical connections between neurons receiving somatosensory cortical input and motor output neurons of the cortex.

Connections between motor cortical neurons receiving somatosensory inputs from area 2 and large pyramidal cells in layer V were examined in the cat via intracellular injection of biocytin and immunohistochemistry of nonphosphorylated neurofilament proteins (npNFP). Biocytin was injected into pyramidal cells in layers II/III of the motor cortex that responded monosynaptically and polysynaptically to microstimulation of the somatosensory cortex and subsequently stained black by the avidin-biotinylated peroxidase complex method with diaminobenzidine (DAB) and nickel. By using a monoclonal antibody SMI-32 and a modified peroxidase-antiperoxidase method with Tris-aminophenyl-methane (TAPM) and p-cresol as a chromogen, pyramidal cells in layers III and V of the motor cortex were stained red for npNFP. In particular, all the large pyramidal cells in layer V, Betz cells, displayed intense npNFP immunoreactivity not only in the perikarya but also in the dendrites. Double staining with DAB/nickel and TAPM/p-cresol showed that biocytin-filled axon varicosities of the pyramidal cells, which were thought to receive monosynaptic inputs from area 2, made contacts with npNFP-positive dendrites in layers I-III around the biocytin-injected cell and in layers V-VI beneath the cell. The present results suggest that the corticocortical input from area 2 to pyramidal cells in layers II/III of the motor cortex is transferred to layer V pyramidal cells, including Betz cells, as well as to neighboring layer II/III pyramidal cells. Since tetanic stimulation of the somatosensory cortex reportedly produces long-term potentiation in layer II/III cells of the motor cortex, it seems reasonable to assume that a given area of the somatosensory cortex can produce a long-lasting change in the activity of a given group of output cells in the motor cortex.

Animals↗
PubMed1996

Inhibition synchronizes sparsely connected cortical neurons within and between columns in realistic network models.

Networks of compartmental model neurons were used to investigate the biophysical basis of the synchronization observed between sparsely-connected neurons in neocortex. A model of a single column in layer 5 consisted of 100 model neurons: 80 pyramidal and 20 inhibitory. The pyramidal cells had conductances that caused intrinsic repetitive bursting at different frequencies when driven with the same input. When connected randomly with a connection density of 10%, a single model column displayed synchronous oscillatory action potentials in response to stationary, uncorrelated Poisson spike-train inputs. Synchrony required a high ratio of inhibitory to excitatory synaptic strength; the optimal ratio was 4 : 1, within the range observed in cortex. The synchrony was insensitive to variation in amplitudes of postsynaptic potentials and synaptic delay times, even when the mean synaptic delay times were varied over the range 1 to 7 ms. Synchrony was found to be sensitive to the strength of reciprocal inhibition between the inhibitory neurons in one column: Too weak or too strong reciprocal inhibition degraded intra-columnar synchrony. The only parameter that affected the oscillation frequency of the network was the strength of the external driving input which could shift the frequency between 35 to 60 Hz. The same results were obtained using a model column of 1000 neurons with a connection density of 5%, except that the oscillation became more regular. Synchronization between cortical columns was studied in a model consisting of two columns with 100 model neurons each. When connections were made with a density of 3% between the pyramidal cells of each column there was no inter-columnar synchrony and in some cases the columns oscillated 180 degrees out of phase with each other. Only when connections from the pyramidal cells in each column to the inhibitory cells in the other column were added was synchrony between the columns observed. This synchrony was established within one or two cycles of the oscillation and there was on average less than 1 ms phase difference between the two columns. Unlike the intra-columnar synchronization, the inter-columnar synchronization was found to be sensitive to the synaptic delay: A mean delay of greater than 5 ms virtually abolished synchronization between columns.

Cerebral Cortex↗
PubMed1988

Medullary and mesencephalic pathways and connections of lateral line neurons of the spiny dogfish Squalus acanthias.

The neuronal connections of the electrosensory dorsal and the mechanosensory medial octavolateralis nuclei of the spiny dogfish Squalus acanthias were studied by horseradish peroxidase, autoradiographic and axonal degeneration methods. Efferents from each nucleus, in addition to extensive commissural components, give rise to ipsilateral and contralateral lemnisci that ascend to midbrain levels and terminate among the cells of the lateral mesencephalic nucleus (LMN). Within LMN, electrosensory and mechanosensory neurons distribute dorsolateral and ventromedial in position, respectively. Ascending fibers of both modalities also terminate within the central zone of the optic tectum. The LMN of spiny dogfish sharks that possess a primitive pattern of midbrain organization is homologous to parts of the lateral mesencephalic nuclear complex of batoids that possess a more derived pattern of midbrain organization. Other fiber connections of the dorsal and medial octavolateralis nuclei appear to differ from each other, indicating that electrosensory and mechanosensory lateral line information is carried over separate pathways at least to midbrain levels of the brain stem. For example, nucleus B, a feedback center, occupies a position in the descending lateral line pathways of sharks and skates similar to nucleus praeeminentialis of many electrosensory teleosts. The dorsal octavolateralis nucleus of sharks and skates receives afferents from nucleus B but there is no evidence that nucleus B directly feeds back to the medial octavolateralis nucleus of the spiny dogfish. Moreover, unlike the dorsal nucleus, the medial nucleus of Squalus is reciprocally linked with the octaval system.

Animals↗
PubMed1998

Selective neuronal vulnerability and specific glial reactions in hippocampal and neocortical organotypic cultures submitted to ischemia.

Neurons from cerebral neocortex and hippocampus exhibit a striking difference in vulnerability to transient global ischemia. In order to study the contribution of neuronal connections and neuron-glia interactions to this variation in neuronal vulnerability, we used hippocampal and neocortical cultures submitted to various periods of histotoxic ischemia. Organotypic cultures were exposed at 37 degrees C for 0, 7, 30 and 60 min to a glucose-free NaCN-containing medium. Histological analysis using thionin staining and MAP2 immunostaining showed differences in the temporal profile of neuronal damage in hippocampal and neocortical structures, i.e., in decreasing order, CA1 (7 min) > CA3 and neocortical layers II, III, V, VI (30 min) > DG and neocortical layer IV (60 min). In parallel to the neurodegeneration study, the time course and the regional pattern of microglial and astroglial changes were also examined using GS-B4 isolectin and GFAP as immunohistochemical markers, respectively. The GS-B4 isolectin staining revealed an early (at 7 min for the hippocampus) and a specific microglial activation located in areas undergoing neuronal damage. For both organotypic cultures, astrogliosis occurred later (after 30 min of stress) with no specific regional distribution. Both hippocampal and neocortical cultures submitted to histotoxic ischemia allowed the replication of many of the cellular events observed in response to global ischemia in vivo. These findings support the hypothesis that neuron-neuron connections as well as interactions between neurons and glial cells are essential to reproduce in vitro the selective neuronal vulnerability described in vivo.

Adaptation, Physiological↗
PubMed2005

Synaptic plasticity in micropatterned neuronal networks.

Synaptic plasticity is thought to be of central importance for information processing by the nervous system. Additionally, specific neuronal connectivity patterns in the brain are implicated to play a role in the perception, processing and storage of incoming signals. Experimental control over connectivity within functional neuronal networks is therefore a promising approach in research on signal transduction and processing by the nervous system. A cell culture system is presented that allows experimental determination of neuronal connectivity patterns in an in vitro network. Rat embryonic cortical neurons were grown on patterns of extracellular matrix proteins applied to polystyrene substrates by microcontact printing. Cells comply well with the pattern and form synaptic connections along the experimentally defined pathways. Chemical synapses identified by double patch-clamp measurement showed paired pulse depression as well as frequency-dependent depression in response to trains of stimuli. This type of short-term plasticity has similarly been reported by others in brain slices. Thus, the system reproduces features central for neuronal information processing while the architecture of the network is experimentally manipulable. The ability to tailor the geometry of functional neuronal networks offers a valuable tool both for fundamental questions in neuroscientific research and a wide range of biotechnological applications.

Action Potentials↗
PubMed2001

Noninvasive neuroelectronic interfacing with synaptically connected snail neurons immobilized on a semiconductor chip.

A hybrid circuit of a semiconductor chip and synaptically connected neurons was implemented and characterized. Individual nerve cells from the snail Lymnaea stagnalis were immobilized on a silicon chip by microscopic picket fences of polyimide. The cells formed a network with electrical synapses after outgrowth in brain conditioned medium. Pairs of neurons were electronically interfaced for noninvasive stimulation and recording. Voltage pulses were applied to a capacitive stimulator on the chip to excite the attached neuron. Signals were transmitted in the neuronal net and elicited an action potential in a second neuron. The postsynaptic excitation modulated the current of a transistor on the chip. The implementation of the silicon-neuron-neuron-silicon circuit constitutes a proof-of-principle experiment for the development of neuroelectronic systems to be used in studies on neuronal signal processing, neurocomputation, and neuroprosthetics.

Animals↗
PubMed1996

The 'functional connection' of neurones in relation to behavioural states in rats.

In order to investigate whether dynamics of neuronal networks change during differing behavioural states, the 'functional connection' between neurones in the rat vibrissal sensorimotor system during two different behavioural states (active vs passive whiskering) were revealed using time-dependent scatter diagrams. The functional connection between neurones in the vibrissal motor (MCx) and sensory (SCx) cortices and the superior colliculus (SC) changed depending on the behavioural state. In the rat vibrissal system, the pattern of correlated activities among neurones in the MCx, SCx and SC may play an important role in determining behaviour.

Animals↗
PubMed2004

Keeping sensory cells and evolving neurons to connect them to the brain: molecular conservation and novelties in vertebrate ear development.

The evolution of the mechanosensory cellular module and the molecular details that regulate its development has included morphological modifications of these cells as well as the formation of larger assemblies of mechanosensory cell aggregates among metazoans. This has resulted in a wide diversity of mechanosensory organs. The wide morphological diversity of organs, including the associated morphological modifications of the mechanosensory cells, suggests parallel evolution of these modules and their associated organs. This morphological diversity is in stark contrast to the molecular conservation of developmental modules across phyla. These molecular data suggest that the evolution of mechanosensory transduction might have preceded that of distinct cellular differentiation. However, once a molecular network governing development of specialized cells involved in mechanosensory transduction evolved, that molecular network was preserved across phyla. Present data suggest that at least the common ancestor of triploblastic organisms, perhaps even the common diploblastic ancestor of bilaterian metazoans, had molecular and cellular specializations for mechanosensation. It is argued that the evolution of multicellular organs dedicated to specific aspects of mechanosensation, such as gravity and sound perception, are evolutionary transformations that build on this conserved molecular network for cellular specialization, but reflect distinct morphological solutions. We propose that the sensory neurons, connecting the craniate ear with the brain, are a derived feature of craniates, and possibly chordates, that came about through diversification of the lineage forming mechanosensory cells during development. This evolutionarily late event suggests a heterochronic shift, so that sensory neurons develop in mammals prior to mechanosensory hair cells. However, sensory neuron development is connected to hair cell development, likely in a clonal relationship. The theme of cellular conservation is reiterated in two examples of chordate otic diversification: the evolution of the horizontal canal system and the evolution of the basilar papilla/cochlea. It is suggested that here again, cellular multiplication and formation of a special epithelium predates the functional transformation to an 'organ' system for horizontal angular acceleration and sound pressure reception, respectively. Overall, evolution of the vertebrate ear needs to be understood as an interplay between and utilization of two gene networks or modules. One is at the level of the molecularly and developmentally conserved mechanosensory cellular module. The other is an increased complexity in the morphology of both adult mechanosensory cells and organs by the addition of end-stage and novel features and associated gene networks to detect specific aspects of mechanosensory stimuli.

Animals↗