Alzheimer´s disease can cause epileptic seizure activity in a CA3-CA1 tripartite synapse: A computational study

Occurrence of seizure in some Alzheimer´s disease (AD) patients suggests that the mechanisms involved in pathology of AD may also give rise to occurrence of neural hyperexcitability. Among the hallmarks of the AD is accumulation of amyloid beta (Aβ) peptide which has different effects on neural circuitry. Several observations indicate that most probably increase in Aβ results in structural and functional changes including increase in conductance of synaptic NMDA receptor (NMDAR) channels, blockage of A-type potassium channel, enhancing glutamate release probability at hippocampal synapse and decrease in synaptic glutamate uptake. To examine these hypotheses and to find out about the possible cause of epileptic activity in AD patients, a mathematical model of a tripartite synapse including pre- and post-synaptic neurons and an astrocyte was used. We modified an already developed mathematical tripartite model in order to create a test bed for studying different behaviors of hippocampal neuron under different pathological conditions. To this end, we implemented different effects of accumulation of Aβ peptide on neuronal responses in the model. Results indicated that accumulation of Aβ peptide cause seizure in the form of increasing number of action potentials and instantaneous firing frequency in post-synaptic neurons.