Activity Of Nerve Cells Research Articles

Identifying the workhorse of working memory

Working Memory Working memory allows us to keep behaviorally relevant information in mind over a short period of time. Liu et al. trained mice to remember a smell for a short period after it had been removed. Manipulating nerve cell activity in the mouse medial prefrontal cortex during this period interfered with the mice's performance when learning what they were supposed to do when they then smelled the same or a different odor. Once the animals were well trained on the task, the same manipulations did not affect performance. Science , this issue p. [458][1] [1]: /lookup/doi/10.1126/science.1256573

MicroRNAs and synaptic plasticity--a mutual relationship.

MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain- and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.

Nerve Cells and Neuroglia

There are said to be 27,000,000,000 nerve cells in the human brain and there are about ten times as many neuroglial cells. On the whole, nerve cells are large and glial cells are small, so that their weights are about equal. The cytology of nerve cells does not provide any really startling information. There is a nucleus and a nucleolus complete with sex chromatin, and in the cytoplasm there is Nissl substance formed of RNA and endoplasmic reticulum, mitochondria carrying respiratory enzymes, and lipochromes. Fairly certainly the RNA is concerned with the synthesis of proteins which move out along the axon, and the rate of protein synthesis is increased during axon regeneration. The rate of oxygen uptake is very high, and weight for weight is said to be higher than that in any other cell. Its measurement presents great difficulties, as oxygen uptake of nervous tissue in vivo gives values 5 to 100 times those obtained in vitro. The metabolic activity of nerve cells is believed to increase about five times during and after nervous activity. At the same time, the amounts of cytochrome oxidase and RNA present increase, and there is an increased ammonia production suggesting proteolysis. Excessive activity is said to cause a decrease in cytoplasmic protein and a decrease in RNA. There is a vast literature on cytological changes in cells in overaction, exhaustion and after deprivation of sleep, but there cannot be said to be a coherent body of observed facts, let alone a satisfactory biochemical interpretation of the facts.

Modeling Neural Activity

This paper provides an overview of different types of models for studying activity of nerve cells and their networks with a special emphasis on neural oscillations. One part describes the neuronal models based on the Hodgkin and Huxley formalism first described in the 1950s. It is discussed how further simplifications of this formalism enable mathematical analysis of the process of neural excitability. The focus of the paper’s second component is on network activity. Understanding network function is one of the important frontiers remaining in neuroscience. At present, experimental techniques can only provide global recordings or samples of the activity of the huge networks that form the nervous system. Models in neuroscience can therefore play a critical role by providing a framework for integration of necessarily incomplete datasets, thereby providing insight into the mechanisms of neural function. Network models can either explicitly contain individual network nodes that model the neurons, or they can be based on representations of compound population activity. The latter approach was pioneered by Wilson and Cowan in the 1970s. Finally I provide an overview and discuss how network models are employed in the study of neuronal network pathology such as epilepsy.

Heme oxygenase-1 (HO-1) upregulation delays morphological and oxidative damage induced in an excitotoxic/pro-oxidant model in the rat striatum

Quinolinic acid (QA)-induced overactivation of N-methyl-d-aspartate receptors yields excitotoxicity, oxidative stress and mitochondrial dysfunction, which altogether contribute to trigger a wide variety of toxic pathways with biochemical, behavioral and neuropathological alterations similar to those observed in Huntington’s disease. Noteworthy, in the brains of these patients, increased expression of heme oxygenase-1 (HO-1) levels can be found. It has been proposed that this enzyme can exert a dual role, as it can be either protective or deleterious to the CNS. While some evidence indicates that its overexpression affords cellular anti-oxidant protection due to decreased concentrations of its pro-oxidative substrate heme group, and increased bilirubin levels, other reports established that high HO-1 expression and activity may result in a pro-oxidizing atmosphere due to a release of Fe2+. In this work, we examined the temporal evolution of oxidative damage to proteins, HO-1 expression, immunoreactivity, total activity, and cell death after 1, 3, 5 and 7days of an intrastriatal QA infusion (240nmol/μl). QA was found to induce cellular degeneration, increasing carbonylated proteins and generating a transitory response in HO-1 mRNA, protein content, and immunoreactivity and activity in nerve cells. In order to study the role of HO-1 in the QA-induced cellular death, the tin protoporphyrin IX (SnPP), a well-known HO inhibitor, was administered to rats (30μmol/kg, i.p.). The administration of SnPP to animals treated with QA inhibited the HO activation, and exacerbated the striatal cell damage induced by QA. Our findings reveal a potential modulatory role of HO-1 in the toxic paradigm evoked by QA in rats. This evidence provides a valuable tool for further approaches on HO-1 regulation in neurotoxic paradigms.

Kinin-mediated inflammation in neurodegenerative disorders

The mediatory role of kinins in both acute and chronic inflammation within nervous tissues has been widely described. Bradykinin, the major representative of these bioactive peptides, is one of a few mediators of inflammation that directly stimulates afferent nerves due to the broad expression of specific kinin receptors in cell types in these tissues. Moreover, kinins may be delivered to a site of injury not only after their production at the endothelium surface but also following their local production through the enzymatic degradation of kininogens at the surface of nerve cells. A strong correlation between inflammatory processes and neurodegeneration has been established. The activation of nerve cells, particularly microglia, in response to injury, trauma or infection initiates a number of reactions in the neuronal neighborhood that can lead to cell death after the prolonged action of inflammatory substances. In recent years, there has been a growing interest in the effects of kinins on neuronal destruction. In these studies, the overexpression of proteins involved in kinin generation or of kinin receptors has been observed in several neurologic disorders including neurodegenerative diseases such Alzheimer’s disease and multiple sclerosis as well as disorders associated with a deficiency in cell communication such as epilepsy. This review is focused on recent findings that provide reliable evidence of the mediatory role of kinins in the inflammatory responses associated with different neurological disorders. A deeper understanding of the role of kinins in neurodegenerative diseases is likely to promote the future development of new therapeutic strategies for the control of these disorders. An example of this could be the prospective use of kinin receptor antagonists.

Cellular, Molecular and Signaling Mechanisms in Neuro-Immune Interactions Under Stress

The role of Interleukin-1/Interleukin-1 (IL-1/IL-1) production and blood levels, as well as ligand-receptor interactions of IL-1 with locating on immune and nerve target cells have been analyzed. Intracellular signal transduction via the sphingomyelin pathway during the development of stress reaction was also investigated. In mice stress of different durations and intensities induces an increase in the concentration of glucocorticoid hormones and IL-1/IL-1 in blood. Thymocytes and lymphocytes responded to the concomitant actions of IL-1, which correlated with the changes in the humoral immune response. These events coincided with stress-induced changes in the activity of neutral-sphingomyelinase, the key enzyme of the sphingomyelin cascade, in membrane fractions of both the mouse cerebral cortex and thymocytes. It is indicated that changes in functional activity of immune and nerve cells: e.g. proliferative activity of lymphocytes and thymocytes, cytotoxic activity of splenic natural killer (NK) cells, the intensity of cytokine signal transduction in the cells of the immune and neuroendocrine system, can define the disturbances in the immune system and the impairment of neural-immune interactions under stress.

Human ScFv that block sodium ion channel activity of tetrodotoxin

Tetrodotoxin (TTX) is a heterocyclic guanidinium alkaloid (C11H17N3O8) with molecular mass of ∼320 Da. The TTX and toxic analogs block sodium ion activity of mammalian nerve cells resulting in failure to conduct nerve impulse which manifested clinically in host as variable degrees of organ paralysis. Human intoxication occurs after consuming food containing the toxins. Current treatment of the poisoning is supportive and symptomatic. There has been no specific drug or antidote for the TTX mediated malady. In this study, phage clones displaying human single chain antibody fragments (HuScFv) were selected from a human ScFv phage display library. HuScFv derived from phagemid transformed Escherichia coli clones (clones s16 and s35) bound to the TTX as tested by indirect ELISA and band shift assay. Homology modeling and molecular docking revealed that VL domain of the s16-HuScFv interacted with the hydroxyl groups of C6, C9, C10 and C11 of the TTX by means of Tyr 223, Ser226 and Tyr228, while the Asp53 and Asp55 of the VH domain of s35-HuScFv interacted with the positions 1 and 2 of the guanidinium group and the hydroxyl groups at C9 and C10 of the TTX. The s16- and s35-HuScFv neutralized the TTX bioactivity in nerve cell based- and mouse bio-assays. Moreover, the HuScFv could rescue the intoxicated mice from the TTX mediated lethality. Thus, the HuScFv derived from the transformed E. coli clones have high potential as a safe, effective and specific therapeutic remedy for TTX intoxication in humans and warrant further trials.

Extracellular cysteine (Cys)/cystine (CySS) redox regulates metabotropic glutamate receptor 5 activity

Extracellular cysteine (Cys)/cystine (CySS) redox potential (Eh) has been shown to regulate diverse biological processes, including enzyme catalysis, gene expression, and signaling pathways for cell proliferation and apoptosis, and is sensitive to aging, smoking, and other host factors. However, the effects of extracellular Cys/CySS redox on the nervous system remain unknown. In this study, we explored the role of extracellular Cys/CySS Eh in metabotropic glutamate receptor 5 (mGlu5) activation to understand the mechanism of its regulation of nerve cell growth and activation. We showed that the oxidized Cys/CySS redox state (0 mV) in C6 glial cells induced a significant increase in mGlu5-mediated phosphorylation of extracellular signal-regulated kinase (ERK), blocked by an inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (MEK), U0126, a nonpermeant alkylating agent, 4-acetamide-4′-maleimidylstilbene-2,2′-disulfonic acid (AMS), and a specific mGlu5 antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), respectively. ERK phosphorylation under oxidized extracellular Cys/CySS Eh was confirmed in mGlu5-overexpressed human embryonic kidney 293 (HEK293) cells. Oxidized extracellular Cys/CySS Eh also stimulated the generation of intracellular reactive oxygen species (ROS) involved in the phosphorylation of ERK by mGlu5. Moreover, activation of mGlu5 by oxidized extracellular Cys/CySS Eh was found to affect expression of NF-κB and inducible nitric oxide synthase (iNOS). The results also showed that extracellular Cys/CySS Eh involved in the activation of mGlu5 controlled cell death and cell activation in neurotoxicity. In addition, plasma Cys/CySS Eh was found to be associated with the process of Parkinson’s disease (PD) in a rotenone-induced rat model of PD together with dietary deficiency and supplementation of sulfur amino acid (SAA). The effects of extracellular Cys/CySS Eh on SAA dietary deficiency in the rotenone-induced rat model of PD was almost blocked by MPEP pretreatment, further indicating that oxidized extracellular Cys/CySS Eh plays a role in mGlu5 activity. Taken together, the results indicate that mGlu5 can be activated by extracellular Cys/CySS redox in nerve cells, which possibly contributes to the process of PD. These in vitro and in vivo findings may aid in the development of potential new nutritional strategies that could assist in slowing the degeneration of PD.

Slow intrinsic rhythm in the koniocellular visual pathway

Slow rhythmic changes in nerve-cell activity are characteristic of unconscious brain states and also may contribute to waking brain function by coordinating activity between cortical and subcortical structures. Here we show that slow rhythms are exhibited by the koniocellular (K) pathway, one of three visual pathways beginning in the eye and projecting through the lateral geniculate visual relay nucleus to the cerebral cortex. We recorded activity in pairs and ensembles of neurons in the lateral geniculate nucleus of anesthetized marmoset monkeys. We found slow rhythms are common in K cells but are rare in parvocellular and magnocellular cell pairs. The time course of slow K rhythms corresponds to subbeta (<10 Hz) EEG frequencies, and high spike rates in K cells are associated with low power in the theta and delta EEG bands. By contrast, spontaneous activity in the parvocellular and magnocellular pathways is neither synchronized nor strongly linked to EEG state. These observations suggest that parallel visual pathways not only carry different kinds of visual signals but also contribute differentially to brain circuits at the first synapse in the thalamus. Differential contribution of sensory streams to rhythmic brain circuits also raises the possibility that sensory stimuli can be tailored to modify brain rhythms.

Probing the regulation of TASK potassium channels by PI(4,5)P2 with switchable phosphoinositide phosphatases

TASK channels are background K+ channels that contribute to the resting conductance in many neurons. A key feature of TASK channels is the reversible inhibition by Gq-coupled receptors, thereby mediating the dynamic regulation of neuronal activity by modulatory transmitters. The mechanism that mediates channel inhibition is not fully understood. While it is clear that activation of Gαq is required, the immediate signal for channel closure remains controversial. Experimental evidence pointed to either phospholipase C (PLC)-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) as the cause for channel closure or to a direct inhibitory interaction of active Gαq with the channel. Here, we address the role of PI(4,5)P2 for G-protein-coupled receptor (GPCR)-mediated TASK inhibition by using recently developed genetically encoded tools to alter phosphoinositide (PI) concentrations in the living cell.When expressed in CHO cells, TASK-1- and TASK-3-mediated currents were not affected by depletion of plasma membrane PI(4,5)P2 either via the voltage-activated phosphatase Ci-VSP or via chemically triggered recruitment of a PI(4,5)P2-5'-phosphatase. Depletion of both PI(4,5)P2 and PI(4)P via membrane recruitment of a novel engineered dual-specificity phosphatase also did not inhibit TASK currents. In contrast, each of these methods produced robust inhibition of the bona fide PI(4,5)P2-dependent channel KCNQ4. Efficient depletion of PI(4,5)P2 and PI(4)P was further confirmed with a fluorescent phosphoinositide sensor. Moreover, TASK channels recovered normally from inhibition by co-expressed muscarinic M1 receptors when resynthesis of PI(4,5)P2 was prevented by depletion of cellular ATP. These results demonstrate that TASK channel activity is independent of phosphoinositide concentrations within the physiological range. Consequently, Gq-mediated inhibition of TASK channels is not mediated by depletion of PI(4,5)P2.

Evidence for dopamine release and metabolism beyond the control of nerve impulses and dopamine receptors in rat substantia nigra.

In rat substantia nigra a biphasic disappearance curve of dopamine (DA) was seen after tyrosine hydroxylase inhibition by alpha-methyl-p-tyrosine (alpha-MT): the initial phase had a fast turnover and a half life of 0.5 h and the later phase had an extremely slow turnover. In contrast to the effects in striatum, neither haloperidol nor apomorphine influenced alpha-MT-induced DA disappearance in the substantia nigra. Furthermore, inhibition of impulse flow by gamma-butyrolactone prevented DA disappearance in striatum but not in the substantia nigra. Measurements of DA and 3-methoxytyramine following treatment with inhibitors of monoamine oxidase (pargyline) and catechol-O-methyl transferase (tropolone) indicated that O-methylation is a more important metabolic pathway in the substantia nigra than in the striatum. The data are interpreted to indicate that the release and metabolism of DA in the substantia nigra are largely beyond the control of nerve impulses and DA receptors. It is suggested that such an arrangement forms an important feature of autoreceptor-mediated feedback control of DA nerve cell activity.

Animal Studies Suggest Alzheimer's Responds to Blood-Pressure Drug

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessAnimal Studies Suggest Alzheimer's Responds to Blood-Pressure DrugJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:7 Jan 2011https://doi.org/10.1176/pn.46.1.psychnews_46_1_026AbstractDrugs that activate potassium channels in neurons might prove effective in treating Alzheimer's disease, new research suggests.The research was headed by Mark Mattson, Ph.D., chief of the Laboratory of Neurosciences at the National Institute on Aging in Baltimore.Abnormalities in potassium-channel function have been found in neurons taken from patients with Alzheimer's, suggesting that potassium channels might be a valuable focus for therapeutic research efforts. Neurons from patients with Alzheimer's also demonstrate compromised energy metabolism and calcium dysregulation. For such reasons, Mattson and his colleagues decided to see whether the medication diazoxide might have therapeutic potential in 3xTgAD mice.Diazoxide is known to activate potassium channels and was used decades ago to treat high blood pressure. Today it is used to treat hyperinsulinism caused by a defect in potassium channels. The 3xTgAD mice are genetically modified so that they develop progressive Alzheimer-like brain pathology, such as amyloid plaques and tau tangles, and so that they experience cognitive and neuropsychiatric-like symptoms of dementia, such as deficits in learning and memory.The researchers studied two groups of the 3xTgAD mice. One group was given diazoxide in drinking water for eight months; the other was given a placebo. After eight months, the diazoxide group outperformed the placebo group on both learning and memory. Moreover, the brain tissue of the diazoxide group, in comparison with that of the placebo group, showed fewer deposits of amyloid and tau proteins, the hallmarks of Alzheimer's; less damage due to oxidative stress; and better blood flow.“Our findings show that diazoxide can ameliorate molecular, cytopathological, and behavioral alterations in a mouse model of Alzheimer's disease, suggesting a therapeutic potential for drugs that activate potassium channels in the treatment of Alzheimer's disease,” Mattson and his team said in their paper, which was published in the November 15, 2010, Journal of Alzheimer's Disease.“These intriguing findings open new avenues of basic research that may increase our understanding of how modulating the electrical activity of nerve cells may slow the damage wrought by Alzheimer's disease pathology,” Richard Hodes, M.D., director of the National Institute on Aging, said in an accompanying press release.Drugs that manipulate potassium channels in neurons may also prove helpful in neurological disorders other than Alzheimer's. For example, potassium channels are widely expressed in basal-ganglia neurons and play crucial roles in Parkinson's disease. Thus, drugs that alter these channels might have some therapeutic value as a Parkinson's treatment.An abstract of “K ATP Channel Activator Diazoxide Ameliorates Amyloid-Beta and Tau Pathologies and Improves Memory in the 3xTgAD Mouse Model of Alzheimer's Disease” can be accessed at <http://iospress.metapress.com> by entering “The K ATP Channel Activator Diazoxide” under “Quick Search.” ISSUES NewArchived

The Triune Brain: Limbic Mind Mind Plastic, Emotional Mind

Problem statement: The theory discussed is revealing, as compared to studies on the human brain, the fact that he has inherited the str ucture and organization of three fundamental types of reptiles, ancient or primitive mammals and mammals, or recent evolved. What is very disconcerting is that nature has been able to connect with each othe r and establish a sort of communication between them. Approach: The objective was to focus the study on chemical s ubstances that regulate the activity of nerve cells, neurons. We can define neu romodulators or modulators of behavior because their intervention more or less obvious influence o ur own actions. The method under consideration is the TMS, transcranial magnetic stimulation, a nonin vasive technique of Neurostimulation and neuromodulation which is based on a type of electro magnetic induction of an electric field. Results: This property of TMS allows us to understand the pr ecise moment when a brain region contributes to a certain task, to map the functional connectivity be tween different brain regions, to identify the caus al relationships involved far treated between brain, c ognition and behavior. Conclusion: It 'as certain that the thoughts and experience change the configuratio n of our brain connections, but so can the induced systems, based on the same principle, capable of al tering particularly for therapeutic, rehabilitative or educational, the brain matter on the basis of premi ses of the so-called phenomenon called Hebbian learning based on chemical changes in the cells and synapses known as long-term potentiation.

Minocycline neuroprotection in a rat model of asphyxial cardiac arrest is limited

ObjectiveThe study investigated a possible neuroprotective potency of minocycline in an experimental asphyxial cardiac arrest (ACA) rat model. Clinically important survival times were evaluated thus broadening common experimental approaches. MethodsAdult rats were subjected to 5min of ACA followed by resuscitation. There were two main treatment groups: ACA and sham operated. Relating to minocycline treatment each group consisted of three sub-groups: pre-, post-, and sans-mino, with three different survival times: 4, 7, and 21 days. Neurodegeneration and microgliosis were monitored by immunohistochemistry. Alterations of microglia-associated gene expression were analyzed by quantitative RT-PCR. ResultsACA induced massive nerve cell loss and activation of microglia/macrophages in hippocampal CA1 cell layer intensifying with survival time. After 7 days, minocycline significantly decreased both, neuronal degeneration and microglia response in dependence on the application pattern; application post ACA was most effective. After 21 days, neuroprotective effects of minocycline were lost. ACA significantly induced expression of the microglia-associated factors Ccl2, CD45, Mac-1, F4-80, and Tnfa. Independent on survival time, minocycline affected these parameters not significantly. Expression of iNOS was unaffected by both, ACA and minocycline. ConclusionsIn adult rat hippocampus microglia was significantly activated by ACA. Minocycline positive affected neuronal survival and microglial response temporary, even when applied up to 18h after ACA, thus defining a therapeutically-relevant time window. As ACA-induced neuronal cell death involves acute and delayed events, longer minocycline intervention targeting also secondary injury cascades should manifest neuroprotective potency, a question to be answered by further experiments.

Mach–Zehnder interference microscopy optically records electrically stimulated cellular activity in unstained nerve cells

Dual-beam white light interference microscopy monitors changes in the optical density of the investigated object with high sensitivity. We report on the recording of dynamic changes in a neuron's optical density evoked by extracellular electrical stimulation. These recorded changes were analysed and unambiguously connected to the investigated object, an invertebrate neuron of the pond snail Lymnaea stagnalis. The results provide evidence for the method's applicability in visualizing cellular dynamics purely by evaluating changes in a cell's optical properties.

Picking Your Classmate's Brain: Four Inquiry-Based Experiments about the Human Brain

Four inquiry-based laboratories are described that introduce students to the properties of human brain cells. These experiments require no technical equipment, are inexpensive and safe, and introduce students to genuine research using neuropsychological investigations as a means of studying the properties of brain cells. Students design and conduct an experiment using optical illusions to explore the activity and response of specific nerve cells of the visual system. Some of the successes and pitfalls of such an activity are discussed.

Unraveling Environmental Effects on Mitochondria

Look into any cell today, and you’ll see remnants of ancient bacteria by the thousands. These mitochondria—tiny organelles in the cell that each possess their own DNA—have come under a growing scientific spotlight; scientists increasingly believe they play a central role in many, if not most, human illnesses. Exquisitely sensitive to environmental threats, mitochondria convert dietary sugars into a high-energy molecule—adenosine triphosphate (ATP)—that cells use as fuel. And when mitochondria falter, cells lose power, just as a flashlight dims when its batteries weaken. Now scientists are linking environmental interactions with the mitochondria to an array of metabolic and age-related maladies, including cancer, autism, type 2 diabetes, Alzheimer disease, Parkinson disease, and cardiovascular illness.

Muscarinic Acetylcholine Receptors (mAChRs) in the Nervous System: Some Functions and Mechanisms

This article summarizes some of the effects of stimulating muscarinic receptors on nerve cell activity as observed by recording from single nerve cells and cholinergic synapses in the peripheral and central nervous sytems. It addresses the nature of the muscarinic receptor(s) involved and the ion channels and subcellular mechanisms responsible for the effects. The article concentrates on three effects: postsynaptic excitation, postsynaptic inhibition, and presynaptic (auto) inhibition. Postsynaptic excitation results primarily from the inhibition of potassium currents by M(1)/M(3)/M(5) receptors, consequent upon activation of phospholipase C by the G protein Gq. Postsynaptic inhibition results from M2-activation of inward rectifier potassium channels, consequent upon activation of Gi. Presynaptic inhibition results from M(2) or M(4) inhibition of voltage-gated calcium channels, consequent upon activation of Go. The segregation receptors, G proteins and ion channels, and the corelease of acetylcholine and glutamate from cholinergic fibres in the brain are also discussed.

Modular glass chip system measuring the electric activity and adhesion of neuronal cells—application and drug testing with sodium valproic acid

We developed a modular neurochip system by combining a small (16x16 mm2) glass neurochip (GNC) with a homemade head stage and commercial data acquisition hardware and software. The system is designed for the detection of the electric activity of cultivated nerve or muscle cells by a 52-microelectrode array (MEA). In parallel, cell adhesion can be registered from the electric impedance of an interdigitated electrode structure (IDES). The GNC was tested with various cell lines and primary cells. It is fully autoclavable and re-useable. Murine embryonic primary cells were used as a model system to correlate the electric activity and adhesion of neuronal networks in a drug test with sodium valproic acid. The test showed the advantage of the parallel IDES and MEA measurements, i.e. the parallel detection of cytotoxic and neurotoxic effects. Toxic exposure of the cells during neuronal network formation allows for the characterization of developmental neurotoxic effects even at drug concentrations below the EC50-value for acute neurotoxic effects. At high drug concentrations, the degree of cytotoxic damage can still be assessed from the IDES data in the event that no electric activity develops. The GNC provides optimal cell culture conditions for up to months in combination with full microscopic observability. The 4'' glass wafer technology allows for a high precision of the GNC structures and an economic production of our new system that can be applied in general and developmental toxicity tests as well as in the search for neuro-active compounds.