Connecting Epilepsy and Alzheimer’s Disease: Modeling of Normal and Pathological Rhythmicity and Synaptic Plasticity Related to Amyloidββ (Aββ) Effects

This chapter is motivated by the hidden links between neurodegeneration due to Alzheimer’s disease and temporal lobe epileptic activity. The following argument is based on the multiple effects of $$\beta $$ -amyloid peptides (A $$\beta $$ ) forming these links potentially at molecular, cellular, synaptic, network, as well as system levels. To explore these links a computational framework was discussed, and two parts of the framework, i.e. pathological rhythm generation and altered bidirectional synaptic plasticity have been constructed and analyzed. By using a skeleton network model of the hippocampal rhythm generation it was demonstrated how A $$\beta $$ affects the ability of neurons in hippocampal networks to fire in unison at theta frequency resulting in reduced power of the theta rhythm. The dual qualitative effects of elevated A $$\beta $$ at the synaptic level, i.e. LTD facilitation and LTP impairment is studied by a modified calcium control hypothesis. The modification implemented the $$\beta $$ -amyloid effects on the bidirectional synaptic plasticity and explained well the experimental findings of decreased LTP and increased LTD. The analysis of a kinetic model taking into account the phosphorylation and dephosphorylation pathways associated with potentiation and depression of the AMPA receptor activity supported the biological plausibility of the modification. Such kinds of models offer an integrative perspective to organize scattered data obtained by methods of anatomy, electrophysiology, brain imaging, neurochemistry, behavioral studies, etc. into a coherent picture.