The provided code is a simulation script for a computational model of the neurovascular unit (NVU). The NVU is a complex structure in the brain that facilitates communication between neuronal and vascular components, playing a crucial role in coupling neuronal activity to blood flow—a phenomenon known as neurovascular coupling. This code focuses on several key biological aspects within the NVU, which are crucial for maintaining cerebral blood flow and supporting neural activity. ### Key Biological Components of the Model 1. **Ion Dynamics and Transport**: - **Potassium (K⁺)**: The script models potassium dynamics, which are critical due to K⁺'s role in maintaining the resting membrane potential and repolarizing neurons after action potentials. Potassium concentration changes affect neuronal excitability and influence vascular responses. - **Calcium (Ca²⁺)**: Astrocytic calcium dynamics are modeled, highlighting their role in signaling within the NVU. Calcium influences the release of vasoactive substances from astrocytes, impacting blood vessel dilation. - **Nitric Oxide (NO)**: This gaseous signaling molecule is crucial for vasodilation. The model considers NO production, which directly affects smooth muscle cells in blood vessel walls, leading to changes in cerebral blood flow. 2. **Astrocytes**: - Astrocytes are glial cells that contribute significantly to neurovascular coupling. They respond to neuronal activity by elevating intracellular Ca²⁺ levels, which can activate channels like TRPV4, influencing extracellular potassium space (ECS) and subsequent vascular responses. This model incorporates the role of astrocytes in modulating Ca²⁺ dynamics and signaling pathways crucial for blood flow regulation. 3. **Smooth Muscle Cells and Endothelial Cells (SMCEC)**: - These cells constitute part of the blood vessel wall, playing a pivotal role in modulating vessel diameter. The model simulates how inputs from neuronal and astrocytic sources interact with vascular smooth muscle, affecting vessel constriction and dilation through mechanisms involving calcium and NO. 4. **Neuron Simulation**: - The neuronal component is simulated with parameters for different types of current stimuli, linking neuronal activity directly to NVU responses. The model adjusts neuronal firing rates and neurotransmitter release (e.g., glutamate) impacting astrocytic and vascular behavior. 5. **Wall Mechanics**: - The mechanical properties of blood vessel walls are modeled to understand how biochemical signaling (e.g., through NO) translates into physical changes in vessel diameter, affecting cerebral blood flow (CBF) and volume (CBV). 6. **Integration with Experimental Data**: - The script integrates experimental data, specifically for current type 3 and 4 stimulations, allowing comparisons between model predictions and experimental observations (e.g., cerebral blood flow changes during whisker stimulation). ### Biological Phenomena Modeled - **Neurovascular Coupling**: This critical phenomenon is modeled by simulating how neuronal activity leads to changes in blood vessel diameter and thus blood flow, mediated by astrocytic signaling and NO release. - **Cerebral Blood Flow Regulation**: The model captures how NVU components regulate CBF and CBV, emphasizing the interplay between neuronal stimuli, astrocytic responses, and vascular changes. - **Metabolic Demand and Oxygen Supply**: The switches for oxygen availability and ATP limitation indicate a simulation of metabolic processes, reflecting the NVU's role in meeting neuronal metabolic demands through vascular responses. In summary, this script models the dynamic interactions within the NVU, focusing on how neuronal activity translates into vascular responses via astrocytic signaling and endothelial function, thereby contributing to our understanding of the mechanisms underlying neurovascular coupling.