Computer Model of Synapse Loss During an Alzheimer’s Disease-Like Pathology in Hippocampal Subregions DG, CA3 and CA1—The Way to Chaos and Information Transfer

• Main Authors: Dariusz Świetlik, Jacek Białowąs, Janusz Moryś, Aida Kusiak
• Format: Article
• Language: English
• Published: MDPI AG 2019-04-01
• Series: Entropy
• Subjects: neural networks; Alzheimer’s disease; learning and memory; hippocampus; LTP; theta rhythm; computer simulation
• Online Access: https://www.mdpi.com/1099-4300/21/4/408

The aim of the study was to compare the computer model of synaptic breakdown in an Alzheimer&#8217;s disease-like pathology in the dentate gyrus (DG), CA3 and CA1 regions of the hippocampus with a control model using neuronal parameters and methods describing the complexity of the system, such as the correlative dimension, Shannon entropy and positive maximal Lyapunov exponent. The model of synaptic breakdown (from 13% to 50%) in the hippocampus modeling the dynamics of an Alzheimer&#8217;s disease-like pathology was simulated. Modeling consisted in turning off one after the other EC2 connections and connections from the dentate gyrus on the CA3 pyramidal neurons. The pathological model of synaptic disintegration was compared to a control. The larger synaptic breakdown was associated with a statistically significant decrease in the number of spikes (R = &#8722;0.79, <i>P</i> &lt; 0.001), spikes per burst (R = &#8722;0.76, <i>P</i> &lt; 0.001) and burst duration (R = &#8722;0.83, <i>P</i> &lt; 0.001) and an increase in the inter-burst interval (R = 0.85, <i>P</i> &lt; 0.001) in DG-CA3-CA1. The positive maximal Lyapunov exponent in the control model was negative, but in the pathological model had a positive value of DG-CA3-CA1. A statistically significant decrease of Shannon entropy with the direction of information flow DG-&gt;CA3-&gt;CA1 (R = &#8722;0.79, <i>P</i> &lt; 0.001) in the pathological model and a statistically significant increase with greater synaptic breakdown (R = 0.24, <i>P</i> &lt; 0.05) of the CA3-CA1 region was obtained. The reduction of entropy transfer for DG-&gt;CA3 at the level of synaptic breakdown of 35% was 35%, compared with the control. Entropy transfer for CA3-&gt;CA1 at the level of synaptic breakdown of 35% increased to 95% relative to the control. The synaptic breakdown model in an Alzheimer&#8217;s disease-like pathology in DG-CA3-CA1 exhibits chaotic features as opposed to the control. Synaptic breakdown in which an increase of Shannon entropy is observed indicates an irreversible process of Alzheimer&#8217;s disease. The increase in synapse loss resulted in decreased information flow and entropy transfer in DG-&gt;CA3, and at the same time a strong increase in CA3-&gt;CA1.