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At least 703 records · Page 39Linked to original sources
PubMed2003

Spatiotemporal patterns of excitation and inhibition evoked by the horizontal network in layer 2/3 of ferret visual cortex.

The horizontal network in visual cortex layer 2/3 is implicated in numerous psychophysical and physiological properties. To investigate the spatial and temporal distribution of excitation and inhibition evoked by this network, we used voltage-sensitive dyes to image the responses to focal electrical stimulation in tangential slices of ferret visual cortex layer 2/3. The resulting optical patterns included a diffuse zone of activation near the stimulation site and numerous ovoid domains throughout the slice. In contrast to the fixed anatomy of the horizontal connections, substantial shifts in both space and time were evident in the distribution of population-based neuronal activity during stimulus trains. Both of these shifts relied on inhibitory synaptic potentials, suggesting that inhibition driven by horizontal connections sculpts the distribution of activity in this cortical network.

Animals↗
PubMed1998

Long-range connections synchronize rather than spread intrathalamic oscillations: computational modeling and in vitro electrophysiology.

A thalamic network model was developed based on recent data regarding heterogeneous thalamic reticular (RE) cell axonal arborizations that indicate at least two projection patterns, short-range cluster projections and long-range diffuse projections. The model was constrained based on expected convergence and the biophysical properties of RE and thalamocortical (TC) cells and their synapses. The model reproduced in vitro synchronous slow (3-Hz) oscillatory activity and the known effects of T-channel blockade and cholecystokinin (CCK) application on this activity. Whereas previous models used the speed at which approximately 3-Hz oscillations propagate in vitro to infer the spatial extent of intrathalamic projections, we found that, so long as the gamma-aminobutyric acid-B synaptic conductance was adjusted appropriately, a network with only short-range projections and another network with both short- and long-range projections could both produce physiologically realistic propagation speeds. Although the approximately 3-Hz oscillations propagated at similar speeds in both networks, phase differences between oscillatory activity at different locations in the network were much smaller in the network containing both short- and long-range projections. We measured phase differences in vitro and found that they were similar to those that arise in the network containing both short- and long-range projections but are inconsistent with the much larger phase differences that occur in the network containing only short-range projections. These results suggest that, although they extend much further than do short-range cluster projections, long-range diffuse projections do not spread activity over greater distances or increase the speed at which intrathalamic oscillations propagate. Instead, diffuse projections may function to synchronize activity and minimize phase shifts across thalamic networks. One prediction of this hypothesis is that, immediately after a collision between propagating oscillations, phase gradients should vary smoothly across the thalamic slice. The model also predicts that phase shifts between oscillatory activity at different points along a thalamic slice should be unaffected by T-channel blockers and decreased by suppression of synaptic transmission or application of CCK.

Animals↗
PubMed2000

Cooperative coevolution: an architecture for evolving coadapted subcomponents.

To successfully apply evolutionary algorithms to the solution of increasingly complex problems, we must develop effective techniques for evolving solutions in the form of interacting coadapted subcomponents. One of the major difficulties is finding computational extensions to our current evolutionary paradigms that will enable such subcomponents to "emerge" rather than being hand designed. In this paper, we describe an architecture for evolving such subcomponents as a collection of cooperating species. Given a simple string-matching task, we show that evolutionary pressure to increase the overall fitness of the ecosystem can provide the needed stimulus for the emergence of an appropriate number of interdependent subcomponents that cover multiple niches, evolve to an appropriate level of generality, and adapt as the number and roles of their fellow subcomponents change over time. We then explore these issues within the context of a more complicated domain through a case study involving the evolution of artificial neural networks.

Adaptation, Physiological↗
PubMed2005

What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data.

The extensive physiological data on hippocampal theta rhythm provide an opportunity to evaluate hypotheses about the role of theta rhythm for hippocampal network function. Computational models based on these hypotheses help to link behavioral data with physiological measurements of different variables during theta rhythm. This paper reviews work on network models in which theta rhythm contributes to the following functions: (1) separating the dynamics of encoding and retrieval, (2) enhancing the context-dependent retrieval of sequences, (3) buffering of novel information in entorhinal cortex (EC) for episodic encoding, and (4) timing interactions between prefrontal cortex and hippocampus for memory-guided action selection. Modeling shows how these functional mechanisms are related to physiological data from the hippocampal formation, including (1) the phase relationships of synaptic currents during theta rhythm measured by current source density analysis of electroencephalographic data from region CA1 and dentate gyrus, (2) the timing of action potentials, including the theta phase precession of single place cells during running on a linear track, the context-dependent changes in theta phase precession across trials on each day, and the context-dependent firing properties of hippocampal neurons in spatial alternation (e.g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm.

Action Potentials↗
PubMed1998

Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity.

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

Algorithms↗
PubMed2006

Adrenergic and cholinergic control in the biology of epidermis: physiological and clinical significance.

The presence of an autocrine adrenergic and cholinergic intra/intercellular signal transduction network in the human epidermis contributes significantly to homeostatic and compensatory responses regulating vital functions in keratinocytes and melanocytes. The ligands produced control autocrine and paracrine loops to initiate responses through cognate receptors expressed within the same or adjacent cells. The epidermal adrenergic signal controls calcium homeostasis, cell growth, differentiation, motility, and pigmentation via the beta2 and alpha1 adrenoceptors. The cholinergic system is highly complex comprising both nicotinic and muscarinic receptors with multiple subtypes and this system plays an important role in keratinocyte cell cycle progression, differentiation, directional migration, adhesion, and apoptotic secretion. Moreover, lymphocytes also express adrenergic and cholinergic receptors. Both types of signal transduction receptors are coupled to classical intracellular second messenger pathways, including cAMP-, cGMP-, and calcium-mediated downstream responses. To date, it has been recognized that several dermatoses such as psoriasis, atopic dermatitis, Mal de Meleda, vitiligo, palmoplantar pustulosis, and pemphigus may be mediated, in part, by the non-neuronal adrenergic/cholinergic systems. A detailed understanding of the physiology and pathophysiology of the adrenergic/cholinergic network in the skin could offer the development of specific drugs for novel treatment modalities.

Animals↗
PubMed1978

Endogenous pain control mechanisms: review and hypothesis.

The anatomy, physiology, and pharmacology of an intrinsic neural network that monitors and modulates the activity of pain-transmitting neurons is reviewed. This system can be activated by opiate administration or by electrical stimulation of discrete brainstem sites. Evidence is presented that its pain-suppressing action is mediated in part by endogenous opiatelike compounds (endorphins). This pain suppression system is organized at three levels of the neuraxis: midbrain, medulla, and spinal cord. Activation of neurons in the midbrain periaqueductal gray matter (by electrical stimulation, opiates, and possibly psychological factors) excites neurons of the rostral medulla, some of which contain serotonin. The medullary neurons, in turn, project to and specifically inhibit the firing of trigeminal and spinal pain-transmission neurons. As part of a negative feedback loop, the output of the pain transmission neurons, i.e., pain itself, is an important factor in activating the pain-suppression system. A neural model which incorporates the experimental findings is proposed, and the clinical implications of the model are discussed.

Analgesia↗
PubMed2003

Synaptogenesis and heritable aspects of executive attention.

In humans, changes in brain structure and function can be measured non-invasively during postnatal development. In animals, advanced optical imaging measures can track the formation of synapses during learning and behavior. With the recent progress in these technologies, it is appropriate to begin to assess how the physiological processes of synapse, circuit, and neural network formation relate to the process of cognitive development. Of particular interest is the development of executive function, which develops more gradually in humans. One approach that has shown promise is molecular genetics. The completion of the human genome project and the human genome diversity project make it straightforward to ask whether variation in a particular gene correlates with variation in behavior, brain structure, brain activity, or all of the above. Strategies that unify the wealth of biochemical knowledge pertaining to synapse formation with the functional measures of brain structure and activity may lead to new insights in developmental cognitive psychology.

Alleles↗
PubMed2003

Cbl signaling networks in the regulation of cell function.

Cbl proteins control multiple cellular processes by acting as ubiquitin ligases and multifunctional adaptor molecules. They are involved in the control of cell proliferation, differentiation and cell morphology, as well as in pathologies such as autoimmune diseases, inflammation and cancer. Here we review recent advances in understanding the role of Cbl and the importance of a growing repertoire of Cbl-interacting proteins in the regulation of signaling pathways triggered by growth factors, antigens, cell adhesion, cytokines and hormones. We also address key issues of the nature of proteins that bind Cbl in particular cells, where they are located, and how they are altered or traffic within cells upon stimulation. It is becoming obvious that temporal and spatial changes in Cbl signaling networks are essential for the control of physiological processes in a variety of cells and organs and that their deregulation can result in the development of human diseases.

Animals↗
PubMed2002

Schema design and implementation of the grasp-related mirror neuron system.

Mirror neurons within a monkey's premotor area F5 fire not only when the monkey performs a certain class of actions but also when the monkey observes another monkey (or the experimenter) perform a similar action. It has thus been argued that these neurons are crucial for understanding of actions by others. We offer the hand-state hypothesis as a new explanation of the evolution of this capability: the basic functionality of the F5 mirror system is to elaborate the appropriate feedback - what we call the hand state - for opposition-space based control of manual grasping of an object. Given this functionality, the social role of the F5 mirror system in understanding the actions of others may be seen as an exaptation gained by generalizing from one's own hand to an other's hand. In other words, mirror neurons first evolved to augment the "canonical" F5 neurons (active during self-movement based on observation of an object) by providing visual feedback on "hand state," relating the shape of the hand to the shape of the object. We then introduce the MNS1 (mirror neuron system 1) model of F5 and related brain regions. The existing Fagg-Arbib-Rizzolatti-Sakata model represents circuitry for visually guided grasping of objects, linking the anterior intraparietal area (AIP) with F5 canonical neurons. The MNS1 model extends the AIP visual pathway by also modeling pathways, directed toward F5 mirror neurons, which match arm-hand trajectories to the affordances and location of a potential target object. We present the basic schemas for the MNS1 model, then aggregate them into three "grand schemas" - visual analysis of hand state, reach and grasp, and the core mirror circuit - for each of which we present a useful implementation (a non-neural visual processing system, a multijoint 3-D kinematics simulator, and a learning neural network, respectively). With this implementation we show how the mirror system may learn to recognize actions already in the repertoire of the F5 canonical neurons. We show that the connectivity pattern of mirror neuron circuitry can be established through training, and that the resultant network can exhibit a range of novel, physiologically interesting behaviors during the process of action recognition. We train the system on the basis of final grasp but then observe the whole time course of mirror neuron activity, yielding predictions for neurophysiological experiments under conditions of spatial perturbation, altered kinematics, and ambiguous grasp execution which highlight the importance of the timing of mirror neuron activity.

Animals↗
PubMed1981

Optimal detection of the alpha state in a model of the human electroencephalogram.

A mole of the EEG with waxing, waning and blocking alpha rhythm is described. One parameter is time dependent and simulates the "physiological alpha state' of the EEG generating network. A theoretically optimal detector of this state appears to be prescribed by the model and the statistics of the alpha state parameter. It minimizes the expected false decision rate.

Alpha Rhythm↗
PubMed1990

Dye-induced photopermeabilization and photodegeneration: a lesion technique useful for neuronal tracing.

Using as a neural system the fly retina, which is visually accessible in vivo, we describe a lesion technique that takes advantage of the photodynamic damage produced by extrinsic dyes. Contrary to the photo-inactivation technique described by Miller and Selverston (1979), this technique does not involve intracellular injection, since the dye is applied to the extracellular space of the tissue. This treatment was found to trigger neuronal degeneration and cell permeabilization in fly photoreceptor neurones. We coined the names 'photodegeneration' and 'photopermeabilization' for these two phenomena. While the technique can be used to delete given neurones from the neural circuit after several days' survival time, it was found to produce adequate cytoplasmic labelling for anatomical studies with both light and electron microscopy. Since the area occupied by the degenerating cells is restricted to the light spot imaged onto the nervous tissue, the resolution with this lesion technique can range from single cells to whole neuronal populations. The remarkable precision of the 'photolesions' produced in this way makes this technique a powerful tool for physiological and anatomical investigations on real neural networks, whenever these can be made optically accessible in vivo or in situ.

Animals↗
PubMed1993

The design and implementation of a ventilator-management advisor.

VentPlan is an implementation of the architecture developed by the qualitative-quantitative (QQ) research group for combining qualitative and quantitative computation in a ventilator-management advisor (VMA). VentPlan calculates recommended settings for four controls of a ventilator by evaluating the predicted effects of alternative ventilator settings. A belief network converts clinical diagnoses to distributions on physiologic parameters. A mathematical-modeling module applies a patient-specific mathematical model of cardiopulmonary physiology to predict the effects of alternative ventilator settings. A decision-theoretic plan evaluator ranks the predicted effects of alternative ventilator settings according to a multiattribute-value model that specifies physician preferences for ventilator treatments. Our architecture allows VentPlan to interpret quantitative observations in light of the clinical context (such as the clinical diagnosis). We report a retrospective study of the ventilator-setting changes encountered in postoperative patients in a surgical intensive-care unit (ICU). We conclude that the QQ architecture allows VentPlan to apply a patient-specific physiologic model to calculate ventilator settings that are optimal with respect to a decision-theoretic value model describing physician preferences for setting the ventilator.

Algorithms↗
PubMed2005

High-throughput and multiplexed protein array technology: protein-DNA and protein-protein interactions.

Miniaturized protein arrays address protein interactions with various types of molecules in a high-throughput and multiplexed fashion. This review focuses on achievements in the analysis of protein-DNA and protein-protein interactions. The technological feasibility of protein arrays depends on the different factors that enable the arrayed proteins to recognize molecular partners and on the specificity of the interactions involved. Proteome-scale studies of molecular interactions require high-throughput approaches for both the production and purification of functionally active proteins. Various solutions have been proposed to avoid non-specific protein interactions on array supports and to monitor low-abundance molecules. The data accumulated indicate that this emerging technology is perfectly suited to resolve networks of protein interactions involved in complex physiological and pathological phenomena in different organisms and to develop sensitive tools for biomedical applications.

Cell-Free System↗
PubMed2004

Microelectrode arrays: a new tool to measure embryonic heart activity.

The analysis of the sequential excitation of cardiac tissue is of high relevance, both for clinical pathophysiological purposes, eg, detection of sustained ventricular arrhythmias, as well as for experimental electrophysiology. Clinically, different technical approaches such as single electrode measurements and bipolar mapping electrode catheters have been used. In experimental setups several techniques to record cardiac activity have been proposed. Beside the well-established intracellular current-clamp recordings of action potentials, recent studies have performed extracellularly activation sequence mapping or simultaneous multichannel action potential electrode array measurements. Measurement of extracellularly recorded field potentials (FPs) hereby especially provides detailed information about the origin and spread of excitation in the heart. A similar analytical approach for cardiac FPs advanced the analysis of excitation spread and arrhythmic activity in multicellular preparations like developmental differentiation tissue of mouse embryonic stem cells, multicellular preparations of isolated native embryonic cardiomyocytes or the embryonic heart in toto. The use of substrate-integrated Microelectrode Arrays (MEAs, Multi Channel Systems, Reutlingen, Germany) with 60 electrodes of 10-30 microm diameters on a 100-200 microm grid, coated with porous titanium nitride to minimize the impedance allows recording of FPs at a high signal to noise ratio. The possibility to electrically stimulate the tissue further expands the range of applications and bioassays. It may thus facilitate the evaluation of drug research providing detailed information about the interplay of the complex cardiac network, and might improve the predictability of physiological and pathophysiological conditions or drug effects in embryonic heart tissue.

Action Potentials↗
PubMed2006

Substance P and neurokinin-1 immunoreactivities in the neural circadian system of the Alaskan northern red-backed vole, Clethrionomys rutilus.

The suprachiasmatic nucleus (SCN) of the hypothalamus houses the main mammalian circadian clock. This clock is reset by light-dark cues and stimuli that evoke arousal. Photic information is relayed directly to the SCN via the retinohypothalamic tract (RHT) and indirectly via the geniculohypothalamic tract, which originates from retinally innervated cells of the thalamic intergeniculate leaflet (IGL). In addition, pathways from the dorsal and median raphe (DR and MR) convey arousal state information to the IGL and SCN, respectively. The SCN regulates many physiological events in the body via a network of efferent connections to areas of the brain such as the habenula (Hb) in the epithalamus, subparaventricular zone (SPVZ) of the hypothalamus and locus coeruleus of the brainstem-areas of the brain associated with arousal and behavioral activation. Substance P (SP) and the neurokinin-1 (NK-1) receptor are present in the rat SCN and IGL, and SP acting via the NK-1 receptor alters SCN neuronal activity and resets the circadian clock in this species. However, the distribution and role of SP and NK-1 in the circadian system of other rodent species are largely unknown. Here we use immunohistochemical techniques to map the novel distribution of SP and NK-1 in the hypothalamus, thalamus and brainstem of the Alaskan northern red-backed vole, Clethrionomys rutilus, a species of rodent currently being used in circadian biology research. Interestingly, the pattern of immunoreactivity for SP in the red-backed vole SCN was very different from that seen in many other nocturnal and diurnal rodents.

Alaska↗
PubMed2004

Pontine influences on breathing: an overview.

Historical and contemporary views of the functional organization of the lateral pontine regions influencing breathing are reviewed. In vertebrates, the rhombencephalon generates a breathing rhythm and detailed motor pattern that persist throughout life. Key to this process is an essentially continuous column of neurons extending from the spino-medullary border through the ventrolateral medulla, continuing through the ventral pons and arcing into the dorsolateral medulla. Comparative neuroanatomy and physiology indicate this is a richly interconnected network divided into serial, functionally distinct compartments. Serial compartmentalization of pontomedullary structures related to breathing also reflects the developmental segmentation of the rhombencephalon. However, with migration of cell groups such as the facial nucleus from the pons to the medulla during ontogeny, the boundaries of the adult pons are sometimes difficult to precisely define. Accordingly, a working definition of rostral and caudal pontine boundaries for adult mammals is depicted.

Animals↗
PubMed2006

Elementary metabolite units (EMU): a novel framework for modeling isotopic distributions.

Metabolic flux analysis (MFA) has emerged as a tool of great significance for metabolic engineering and mammalian physiology. An important limitation of MFA, as carried out via stable isotope labeling and GC/MS and nuclear magnetic resonance (NMR) measurements, is the large number of isotopomer or cumomer equations that need to be solved, especially when multiple isotopic tracers are used for the labeling of the system. This restriction reduces the ability of MFA to fully utilize the power of multiple isotopic tracers in elucidating the physiology of realistic situations comprising complex bioreaction networks. Here, we present a novel framework for the modeling of isotopic labeling systems that significantly reduces the number of system variables without any loss of information. The elementary metabolite unit (EMU) framework is based on a highly efficient decomposition method that identifies the minimum amount of information needed to simulate isotopic labeling within a reaction network using the knowledge of atomic transitions occurring in the network reactions. The functional units generated by the decomposition algorithm, called EMUs, form the new basis for generating system equations that describe the relationship between fluxes and stable isotope measurements. Isotopomer abundances simulated using the EMU framework are identical to those obtained using the isotopomer and cumomer methods, however, require significantly less computation time. For a typical (13)C-labeling system the total number of equations that needs to be solved is reduced by one order-of-magnitude (100s EMUs vs. 1000s isotopomers). As such, the EMU framework is most efficient for the analysis of labeling by multiple isotopic tracers. For example, analysis of the gluconeogenesis pathway with (2)H, (13)C, and (18)O tracers requires only 354 EMUs, compared to more than two million isotopomers.

Carbon↗