# Biological Basis of the Code The code provided is a computational model of axonal propagation in the context of Alzheimer's disease. Specifically, it explores how axonal action potential (AP) propagation is affected by dystrophic structures, which are pathological swellings that can form along axons due to neurodegenerative conditions such as Alzheimer's disease. Below are the key biological aspects represented in the code: ## Key Biological Concepts ### 1. **Dystrophic Structures in Alzheimer's Disease** - **Dystrophy in Axons**: These are abnormal, swollen regions that can form as a result of various neuropathological conditions. In Alzheimer's disease, dystrophic neurites are associated with the presence of amyloid plaques. - **Impact on Signal Propagation**: Dystrophic structures can alter how electrical signals (action potentials) travel along an axon, potentially leading to delays, signal degradation, or complete blockage. The code is designed to assess these phenomena by simulating action potential propagation in axons with different characteristics of dystrophy (sealed, passive, and active). ### 2. **Action Potential Propagation** - **Ionic Channels**: The model includes key channel dynamics for sodium (Na_x) and potassium (K_dr) currents, which are fundamental for action potential generation and propagation. The code allows for modification of the maximum conductance of these channels (`gbar_nax` and `gkdrbar_kdr`), reflecting changes in excitability. - **Current Clamping**: The use of `IClamp` to initiate action potentials mimics experimental approaches where controlled current pulses are applied to trigger neural firing. ### 3. **Types of Dystrophy Simulated** - **Sealed Dystrophy**: In this condition, the integrity of the axonal membrane at the site of dystrophy is maintained, such that the axonal conduction might be less impaired. - **Passive Dystrophy**: This is characterized by leakage of ions across the membrane, which can severely disrupt normal action potential propagation due to membrane depolarization and ion concentration imbalances. - **Active Dystrophy**: Here, altered channel dynamics or additional ion conductance pathways are introduced, simulating situations where abnormal ionic activity occurs within the dystrophic region. ### 4. **Morphology and Biophysical Properties** - **Modeling Morphology**: The code defines morphologic features like axonal diameter and length, and representations of the dystrophic regions, such as "Can" (cylindrical section with specific properties related to the dystrophy) and "Stick" (connecting filament). - **Dynamic Changes**: Functions are provided to alter the morphology dynamically, simulating various physical configurations of axonal and dystrophic shapes. ## Biological Implications The computational exploration provided by the code helps to elucidate the potential impacts of axonal dystrophy on neuronal communication in Alzheimer's disease. By simulating different structural and ionic properties at the site of dystrophy, it allows researchers to infer how these changes might contribute to the broader physiological deficits observed in neurodegeneration, such as cognitive decline and neural circuit disruption. Understanding these impacts at the computational level offers insights into potential therapeutic targets, aiming to preserve or restore normal neural function in the presence of dystrophic axonal changes.