Biomedical subjects

Guenter W Gross

Publications and source records attributed to Guenter W Gross.

7 recordsLinked to original sources

PubMed2004

Measuring synchronization in neuronal networks for biosensor applications.

Cultures of neurons can be grown on microelectrode arrays (MEAs), so that their spike and burst activity can be monitored. These activity patterns are quite sensitive to changes in the environment, such as chemical exposure, and hence the cultures can be used as biosensors. One key issue in analyzing the data from neuronal networks is how to quantify the level of synchronization among different units, which represent different neurons in the network. In this paper, we propose a synchronization metric, based on the statistical distribution of unit-to-unit correlation coefficients. We show that this synchronization metric changes significantly when the networks are exposed to bicuculline, strychnine, or 2,3-dioxo-6-nitro-l,2,3,4-tetrahydrobenzoquinoxaline-7-sulphonamide (NBQX). For that reason, this metric can be used to characterize pharmacologically induced changes in a network, either for research or for biosensor applications.

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PubMed2004

Unique responses of auditory cortex networks in vitro to low concentrations of quinine.

The anti-malarial drug quinine has several side effects including tinnitus. The aim of the study was to determine if cultured auditory networks growing on microelectrode arrays exhibited unique dynamic states when exposed to quinine. Eight auditory cortex networks (ACN), eight frontal cortex networks (FCN), and five inferior colliculus networks (ICN) were used in this study. Response of ACNs to quinine was biphasic, with an excitatory phase followed by inhibition. FCNs and ICNs revealed only inhibitory responses. The concentrations at which the spike rate was inhibited by 50% (IC50 mean +/- SE) were 42.5 +/- 3.9, 28.7 +/- 4.8 and 23.9 +/- 2.1 microM for ACNs, FCNs, and ICNs, respectively. Quinine increased the regularity and coordination of bursting in all three tissues. The increased burst pattern regularity of ICNs coupled with the excitatory responses seen only in ACNs between 1 and 10 microM show a unique susceptibility of auditory tissues to quinine that may be related to the underlying mechanism that triggers tinnitus-like activity.

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PubMed2004

Substance identification by quantitative characterization of oscillatory activity in murine spinal cord networks on microelectrode arrays.

This paper presents a novel and comprehensive method to identify substances on the basis of electrical activity and is a substantial improvement for drug screening. The spontaneous activity of primary neuronal networks is influenced by neurotransmitters, ligands, and other substances in a similar fashion as known from in vivo pharmacology. However, quantitative methods for the identification of substances through their characteristic effects on network activity states have not yet been reported. We approached this problem by creating a database including native activity and five drug-induced oscillatory activity states from extracellular multisite recordings from microelectrode arrays. The response profiles consisted of 30 activity features derived from the temporal distribution of action potentials, integrated burst properties, calculated coefficients of variation, and features of Gabor fits to autocorrelograms. The different oscillatory states were induced by blocking neurotransmitter receptors for: (i) GABA(A); (ii) glycine; (iii) GABA(A) and glycine; (iv) all major synaptic types except AMPA, and (v) all major synapses except NMDA. To test the identification capability of the six substance-specific response profiles, five blind experiments were performed. The response features from the unknown substances were compared to the database using proximity measures using the normalized Euclidian distance to each activity state. This process created six identification coefficients where the smallest correctly identified the unknown substances. Such activity profiles are expected to become substance-specific 'finger prints' that classify unique responses to known and unknown substances. It is anticipated that this kind of approach will help to quantify pharmacological responses of networks used as biosensors.

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PubMed2003

A portable microelectrode array recording system incorporating cultured neuronal networks for neurotoxin detection.

Cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds, have been suggested to be useful for both screening known analytes and unknown compounds for acute neuropharmacologic effects. Extracellular recording from cultured neuronal networks provides a means for extracting physiologically relevant activity, i.e. action potential firing, in a noninvasive manner conducive for long-term measurements. Previous work from our laboratory described prototype portable systems capable of high signal-to-noise extracellular recordings from cardiac myocytes. The present work describes a portable system tailored to monitoring neuronal extracellular potentials that readily incorporates standardized microelectrode arrays developed by and in use at the University of North Texas. This system utilizes low noise amplifier and filter boards, a two-stage thermal control system with integrated fluidics and a graphical user interface for data acquisition and control implemented on a personal computer. Wherever possible, off-the-shelf components have been utilized for system design and fabrication. During use with cultured neuronal networks, the system typically exhibits input referred noise levels of only 4-6 microVRMS, such that extracellular potentials exceeding 40 microV can be readily resolved. A flow rate of up to 1 ml/min was achieved while the cell recording chamber temperature was maintained within a range of 36-37 degrees C. To demonstrate the capability of this system to resolve small extracellular potentials, pharmacological experiments with cultured neuronal networks have been performed using ion channel blockers, tetrodotoxin and tityustoxin. The implications of the experiments for neurotoxin detection are discussed.

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PubMed2003

Differential acute effects of fluoxetine on frontal and auditory cortex networks in vitro.

Primary cultures of neuronal networks grown on microelectrode arrays were used to quantify acute effects of fluoxetine (Prozac) on spontaneous spike and burst activity. For frontal cortex cultures, fluoxetine showed consistent inhibitory effects and terminated activity at 10-16 microM. IC(50) mean+/-S.E. for spike rates was 5.4+/-0.7 microM (n=15). For auditory cortex cultures, fluoxetine caused excitation at 1-10 microM, initial inhibition at 15 microM, and activity cessation at 20-25 microM. The spike rate IC(50) was 15.9+/-1.0 microM (n=11). Fluoxetine did not change the action potential waveform shape. However, at high concentrations, it caused total cessation of spike activity on all channels. The inhibition caused by fluoxetine was reversible for both tissues. Based on the results, we conclude that cultures showed repeatable, concentration-dependent sensitivities to fluoxetine but demonstrated tissue-specific responses for frontal and auditory cortex networks. These responses may not be due to the interference with serotonin reuptake, but may be due to a secondary effect on ionic channels.

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PubMed2003

Acute neuropharmacologic action of chloroquine on cortical neurons in vitro.

Chloroquine, a common quinolone derivative used in the treatment of malaria, has been associated with neurologic side-effects including depression, psychosis and delirium. The neuropharmacologic effects of chloroquine were examined on cultured cortical neurons using microelectrode array (MEA) recording and the whole-cell patch clamp technique. Whole-cell patch clamp records under current-clamp mode also showed a chloroquine-induced depression of the firing rate of spontaneous action potentials by approximately 40%, consistent with the observations with the MEA recording, although no changes in either the baseline membrane potential or input resistance were observed. Voltage clamp recordings of spontaneous post-synaptic currents, recorded in the presence of tetrodotoxin, revealed no obvious changes in either the amplitude or rate of occurrence of inward currents with application of chloroquine at 10 microM, suggesting that the fundamental molecular mechanisms underlying spontaneous synaptic transmission may not be affected by acute application of the drug. In contrast, a concentration-dependent inhibition of whole-cell calcium current was observed in the presence of chloroquine. These acute neuropharmacologic changes were not accompanied by cytotoxic actions of the compound, even after exposure of up to 500 microM chloroquine for 7 h. These data suggest that chloroquine can depress in vitro neuronal activity, perhaps through inhibition of membrane calcium channels.

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PubMed2003

Histiotypic electrophysiological responses of cultured neuronal networks to ethanol.

Embryonic murine neuronal networks cultured on substrate-integrated microelectrode arrays were used to quantify acute electrophysiological effects of ethanol by using extracellular, multichannel recording of action potentials. Spontaneously active frontal cortex cultures showed repeatable, concentration-dependent sensitivities to ethanol, with initial inhibition at 20 mM and a spike rate 50% effective concentration (EC50) of 48.8+/-5.4 mM. Ethanol concentrations of greater than 100 mM led to cessation of activity. The ethanol inhibitions up to the maximum tested 160 mM were reversible. Although ethanol did not change the shape of action potentials, unit-specific spike pattern effects were found. At 40 mM, ethanol decreased neuronal firing in 71%, increased firing in 20%, and generated no effect in 9% of all units observed (14 cultures, 200 discriminated units). The effects of combined application of ethanol and fluoxetine were additive. Excellent agreement with findings obtained from experimental studies with animals validates the use of these in vitro systems for alcohol research.

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