Computer Modeling of Alzheimer’s Disease—Simulations of Synaptic Plasticity and Memory in the CA3-CA1 Hippocampal Formation Microcircuit

Abstract

This paper aims to present computer modeling of synaptic plasticity and memory in the CA3-CA1 hippocampal formation microcircuit. The computer simulations showed a comparison of a pathological model in which Alzheimer’s disease (AD) was simulated by synaptic degradation in the hippocampus and control model (healthy) of CA3-CA1 networks with modification of weights for the memory. There were statistically higher spike values of both CA1 and CA3 pyramidal cells in the control model than in the pathological model (p = 0.0042 for CA1 and p = 0.0033 for CA3). A similar outcome was achieved for frequency (p = 0.0002 for CA1 and p = 0.0001 for CA3). The entropy of pyramidal cells of the healthy CA3 network seemed to be significantly higher than that of AD (p = 0.0304). We need to study a lot of physiological parameters and their combinations of the CA3-CA1 hippocampal formation microcircuit to understand AD. High statistically correlations were obtained between memory, spikes and synaptic deletion in both CA1 and CA3 cells.

Computational Modeling of Therapy with the NMDA Antagonist in Neurodegenerative Disease: Information Theory in the Mechanism of Action of Memantine

“…Each module was in charge of a certain aspect of the synaptic transmission process. Formalism from previous research was used in the simulation model [26][27][28][29][30][31]35]. Each module was in charge of a certain aspect of the synaptic transmission process.…”

“…Modeling the plasticity of biological synapses is difficult, but our algorithm closely resembles the biologically important process of long-term potentiation (LTP) while also accounting for forgetting, which is the return of the weight of a given synapse to its initial state in the absence of maintenance mechanisms [26][27][28][29][30][31]. LTP induction happens when there is an action potential on excitatory input and open NMDA channels due to adequate depolarization of the postsynaptic region, Figure 1.…”

“…Computer models of neurons [26] and neural networks [27,28] are two methods for comprehending the nervous system's functioning. Understanding the process of neurodegeneration in Alzheimer's disease is aided by computer models of synaptic degradation in the hippocampus for various stages of synaptic loss [29,30]. Other simulation experiments, on the other hand, demonstrate that generating gamma oscillations in the hippocampus can help with the pathophysiology of Alzheimer's disease [31].…”

“…Using the mathematical framework from earlier simulation research [26][27][28][29][30][31]35], a computer simulation environment of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) and NMDA receptors was established for therapy with the NMDA receptor antagonist-memantine. (1) the biological mechanism of AMPA and NMDA receptor function, (2) simulations of glutamate release inside the synaptic gap following presynaptic stimulation, (3) the mechanism of excitotoxicity, and (4) simulations of memantine treatments at three concentrations: 3, 10, and 30 µM, due to the pattern of long-term potentiation.…”

Coexisting fast–slow dendritic traveling waves in a 3D-array electric field coupled neuronal network

“…[15] By modeling and simulating the state changes of individual neurons during dendritic oscillations in the hippocampus, we have gained a better understanding of the process of dendritic oscillations. [16] The hippocampus was expanded from the middle to simulate the activity of neurons on a square array, which was propagated by two-way synapses between CA1-CA3 regions of the hippocampus. [9,10] This model provides a simplified idea to unfold the hippocampus before simulation but only considers the activity of synaptic transmission pyramidal neurons on one plane, and fails to use models to study electric field coupling and fast and slow waves.…”