Hippocampal slice cultures integrated with multi-electrode arrays: a model for study of long-term drug effects on synaptic activity

Autor: Geoffrey A.R. Mealing, Tanya Comas, Balu Chakravarthy, John G. Mielke, Tarun Ahuja
Rok vydání: 2007
Předmět:
Zdroj: Drug Development Research. 68:84-93
ISSN: 1098-2299
0272-4391
Popis: Technological limitations have restricted the ability to determine chronic drug effects on synaptic function from in vitro preparations. In earlier studies, the extracellular recording duration was limited to less than 10 h and only a distinct population of neurons was examined. To address these limitations, we used organotypic hippocampal slice cultures integrated with planar multi-electrode arrays (MEA-OHSC), which permitted within-slice comparisons and examination of long-term changes across multiple populations of neurons. Long-term potentiation (LTP) is a widely accepted measure of synaptic plasticity, and is believed to be a cellular mechanism underlying learning and memory. Amyloid-β protein (Aβ) is a 40–42 amino acid peptide that is the primary element of senile plaques, a pathological hallmark of Alzheimer's disease (AD). In contrast to earlier studies, MEA-OHSCs allowed for long-term administration of Aβ1–42 to more closely model the chronic nature of AD pathogenesis. Prior to Aβ1–42 exposure, the CA1 region displayed robust potentiation, but afterwards the ability to induce LTP was nearly absent. Spatial analysis illustrated, for the first time, the substantial area of LTP induction, and clearly showed the global loss of this plasticity after long-term Aβ exposure. The MEA-OHSC model characterized here presents an ideal platform for examining the effects chronic exposure of a bioactive compound can have on a cellular correlate of memory. This model could also be used to screen potential therapeutics that may influence synaptic activity. Drug Dev Res 68:84–93, 2007. Published 2007 Wiley-Liss, Inc.; Canadian Crown Copyright
Databáze: OpenAIRE
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