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Content archived on 2024-06-18

Functional and synaptic deficits in cerebral cortical neurons in Alzheimer’s Disease model mice

Objective

Alzheimer’s disease (AD) is the most common neurodegenerative disease, affecting millions of people worldwide and therefore it is fundamental to understand its underlying mechanisms. Although the neuropathologies involved in AD are well-described, the effect of those pathologies on neuronal function are poorly understood. Using a transgenic mouse model of AD that overexpresses human amyloid-beta (a-beta), we will study the effects of a-beta accumulation on neocortical synaptic function and receptive field organization using in vivo intracellular recording and in vivo 2-photon laser-scanning microscopy (2PLSM). We will measure the effect of soluble a-beta on individual synapses by imaging calcium dynamics in dendritic spines of somatosensory cortical neurons in response to whisker stimulation. Responses in transgenic animals will be compared to age-matched controls. This will measure the effects of a-beta on individual synapses in vivo. In addition, we will measure the neurotoxic effects of insoluble a-beta plaques on synaptic function by comparing the calcium dynamics in dendritic spines proximal to plaques to those distant from them. Finally, we will measure the effects of soluble a-beta and plaques on the receptive field organization of Layer II/III somatosensory cortical neurons to quantify the effects of the neuropathology on an intact neocortical network. This study will measure and differentiate between the effects of soluble a-beta and insoluble plaques on cortical function at several levels: at the level of the single synapse (calcium dynamics in dendritic spines), single neuron (electrophysiology of subthreshold inputs and spike outputs) and cortical network (receptive field organization) in the intact animal. This study will therefore fill a crucial gap between the molecular mechanisms of Alzheimer’s Disease and the symptoms of the disease, which are mediated by currently unknown neuronal events.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP7-PEOPLE-ERG-2008
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-ERG - European Re-integration Grants (ERG)

Coordinator

BAR ILAN UNIVERSITY
EU contribution
€ 45 000,00
Address
BAR ILAN UNIVERSITY CAMPUS
52900 Ramat Gan
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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