31 research outputs found

    Microstructural Evolution in Thin Films of Electronic Materials

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    Contains reports on five research projects and a list of publications and theses.Joint Services Electronics Program Contract DAAL03-89-C-0001Semiconductor Research CorporationNational Science FoundationU.S. Army Research OfficeHitachi LimitedIBM Corporatio

    Regulation of fast-spiking basket cell synapses by the chloride channel ClC-2

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    Parvalbumin-expressing, fast-spiking basket cells play key roles in the generation of synchronous, rhythmic population activities in the hippocampus. Here we show that GABAA receptor-mediated synaptic inputs from murine parvalbumin-expressing basket cells are selectively modulated by the membrane voltage- and intracellular chloride-dependent chloride channel ClC–2. These data demonstrate a novel cell type-specific regulation of intracellular chloride homeostasis in the perisomatic region of hippocampal pyramidal neurons. Keywords interneuron; GABAA receptor; excitability; microcircuit; intracellular chloride There are two distinct basket cell classes specialized to provide GABAergic innervation to the perisomatic region of principal cells, the parvalbumin- or cholecystokinin- expressing basket cells (PVBCs or CCKBCs, respectively). The intrinsic and synaptic properties of PVBCs enable them to perform circuit functions related to precise time keeping and generation of network oscillations, whereas CCKBCs are thought to serve as modulators that adapt network activity to behavioral states1,2. Because synapses from PVBCs and CCKBC

    Neurotoxicity of Persistent Organic Pollutants: Possible Mode(s) of Action and Further Considerations

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    Persistent organic pollutants (POPs) are long-lived toxic organic compounds and are of major concern for human and ecosystem health. Although the use of most POPs is banned in most countries, some organochlorine pesticides are still being used in several parts of the world. Although environmental levels of some POPs such as polychlorinated biphenyls (PCBs) have declined, newly emerging POPs such as polybrominated diphenyl ethers (PBDEs) have been increasing considerably. Exposure to POPs has been associated with a wide spectrum of effects including reproductive, developmental, immunologic, carcinogenic, and neurotoxic effects. It is of particular concern that neurotoxic effects of some POPs have been observed in humans at low environmental concentrations. This review focuses on PCBs as a representative chemical class of POPs and discusses the possible mode(s) of action for the neurotoxic effects with emphasis on comparing dose-response and structure-activity relationships (SAR) with other structurally related chemicals. There is sufficient epidemiological and experimental evidence showing that PCB exposure is associated with motor and cognitive deficits in humans and animal models. Although several potential mode(s) of actions were postulated for PCB-induced neurotoxic effects, changes in neurotransmitter systems, altered intracellular signalling processes, and thyroid hormone imbalance are predominant ones. These three potential mechanisms are discussed in detail in vitro and in vivo. In addition, SAR was conducted on other structurally similar chemicals to see if they have a common mode(s) of action. Relative potency factors for several of these POPs were calculated based on their effects on intracellular signalling processes. This is a comprehensive review comparing molecular effects at the cellular level to the neurotoxic effects seen in the whole animal for environmentally relevant POPs
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