Cortical Synaptic IntegrationIn VivoIs Disrupted by Amyloid-β Plaques
| Autor: | Julianne A. Lombardo, Edward A. Stern, Bradley T. Hyman, Brian J. Bacskai, Frank J. Attenello, Gregory A. Hickey |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Genetically modified mouse
Transgene Mice Transgenic Plaque Amyloid Biology medicine.disease_cause Synaptic Transmission Membrane Potentials Amyloid beta-Protein Precursor Mice Alzheimer Disease In vivo Neurites medicine Amyloid precursor protein Animals Evoked Potentials Cerebral Cortex Membrane potential Mutation Pyramidal Cells General Neuroscience Electroencephalography Electric Stimulation Electrodes Implanted Cortex (botany) Disease Models Animal Disease Progression biology.protein Brief Communications Neuroscience Intracellular |
| Zdroj: | The Journal of Neuroscience. 24:4535-4540 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0462-04.2004 |
| Popis: | The accumulation of amyloid-β protein into plaques is a characteristic feature of Alzheimer's disease. However, the contribution of amyloid-β plaques to neuronal dysfunction is unknown. We compared intracellular recordings from neocortical pyramidal neuronsin vivoin APP-Sw (Tg2576 transgenic mice overexpressing amyloid precursor protein with the Swedish mutation) transgenic mice to age-matched nontransgenic cohorts at ages either before or after deposition of cortical plaques. We show that the evoked synaptic response of neurons to transcallosal stimuli is severely impaired in cortex containing substantial plaque accumulation, with an average 2.5-fold greater rate of response failure and twofold reduction in response precision compared with age-matched nontransgenic controls. This effect correlated with the presence of amyloid-β plaques and alterations in neuronal process geometry. Responses of neurons in younger APP-Sw animals, before plaque accumulation, were similar to those in nontransgenic controls. In all cases, spontaneous membrane potential dynamics were similar, suggesting that overall levels of synaptic innervation were not affected by plaques. Our results show that plaques disrupt the synchrony of convergent inputs, reducing the ability of neurons to successfully integrate and propagate information. |
| Databáze: | OpenAIRE |
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