The Project

The project aims at developing a new multi-scale (integrated molecular, cellular and network levels) data-driven in silico model of the hippocampal CA1 region under Alzheimer’s disease conditions.

The main project objectives:

1. Extend the experimental evidence of Amyloid beta (Aβ), Amyloid eta (Aη), Amyloid precursor protein C-terminal peptide (AICD)-related changes in the properties of hippocampal CA1 pyramidal neuron synaptic plasticity, synaptic signal integration and neuronal excitability.
2. Incorporate the dose-dependent effects of Alzheimer’s disease- ...

Alzheimer’s disease affects over 46 million people worldwide, estimated to triple by the year 2050. It has a long preclinical stage and, before any clinical symptoms appear, pathological processes are observed in the hippocampus and entorhinal cortex, key brain structures responsible for memory encoding and retrieval. AD cannot be prevented, halted or cured today, and new interdisciplinary ways are urgently needed for the understanding and treatment of this devastating disease. Recent experimental evidence supports the fundamental role of Alzheimer’s disease-related peptides early in the ...

In this project, we gathered experimental data on the Aβ-, Aη- and AICD-induced alterations in synaptic plasticity, synaptic signal integration and intrinsic excitability of hippocampal CA1 pyramidal neurons. We built a new computational model of hippocampal synaptic plasticity in a mouse, based on NMDAR functioning, and optimized computational models of mouse CA1 pyramidal neurons under control and AD conditions. We showed that synaptic plasticity was impaired in CA1 pyramidal neurons, leading to perturbed memory storage and recall in CA1 networks. We demonstrated that partial blockade of ...