The provided code is a computational model of neuronal activity, focusing on understanding the dynamics of ion channels and synaptic interactions in a neuron, specifically in the context of varying stimulation intensities. This model appears to simulate the impact of neural stimulation on ion concentration and membrane potential, emphasizing the Cl^-, Na^+, and K^+ ion dynamics, synaptic conductances, and ion pump activities, all of which are critical in modeling neuronal excitability and seizure-like activity. ### Biological Components and Processes Modeled 1. **Membrane Potential and Ion Channels:** - **Voltage-Gated Sodium (Na^+) Channels:** The model includes subroutines for the fast sodium current (`G_Na_E`, `m_iNa`, `h_iNa`), crucial for action potential initiation and propagation. The equations and variables reflect the gating kinetics, including activation (`m` gate) and inactivation (`h` gate) processes typical in Hodgkin-Huxley-like models. - **Potassium (K^+) Channels:** This includes delayed rectifier (`G_Kv_E`, `m_iKv`, representing the `Kv` channel) and leak currents (`gg_kl_E`, `G_kl_E`). These components are integral in action potential repolarization and setting the resting membrane potential. - **Calcium-Dependent Potassium Channels (`G_KCa_E`, `m_iKCa`):** Critical in afterhyperpolarization phases which regulate neuronal firing patterns and excitability. - **High-Voltage-Activated Calcium Channels (HVA):** The code models these channels which allow calcium influx (`G_HVA_E`, `m_iHVA`, `h_iHVA`), influencing various cellular processes, including neurotransmitter release and gene expression. 2. **Synaptic Input Parameters:** - **AMPA, NMDA, and GABA Receptors:** Synaptic conductances for excitatory (AMPA and NMDA) and inhibitory (GABA_A) receptors are modeled. These receptors mediate fast synaptic transmission and are involved in the modulation of neuronal excitability and synaptic plasticity. NMDA receptors, in particular, exhibit voltage-dependent Mg^2+ block, which is accounted for in the function `f_NMDA`. - **Dendritic and Somatic Currents:** Consideration of synaptic inputs on different neuronal compartments (dendrite and soma) reflects the spatial diversity in synaptic integration. 3. **Ion Dynamics:** - **K^+, Cl^-, and Na^+ Concentrations:** The model calculates intracellular and extracellular concentrations of key ions (Ko, Cli, Nao, Nai). This is vital for determining Nernst potentials and their resultant impact on the membrane potential and driving forces for ionic currents. - **Na-K Pumps:** The activity of sodium-potassium pumps (`Imaxsoma_E`, `Imaxdend_E`) is also modeled, emphasizing their role in maintaining ion gradients across the neuronal membrane, which is crucial for cell volume regulation and electrochemical stability. 4. **Seizure Activity:** - **Stimulation Intensity and Seizure Duration:** The model explores seizure dynamics induced by varying stimulation intensities (`Hz_max`, `dHz`). The seizure duration (`Tseizure`) is tied to calcium levels and synaptic dynamics, capturing the transition from normal activity to pathological states. 5. **Chloride Homeostasis and KCC2 Activity:** - **KCC2 Transporter (`Vhalf_E`, `Ikcc2_E`):** Reflects the ability of neurons to regulate internal Cl^- concentration, impacting GABAergic inhibition. Disruption in KCC2 functioning is critical in conditions like epilepsy, where excitation-inhibition balance is disturbed. ### Overall Aim The model aims to simulate and understand the complex interplay of ionic currents, synaptic inputs, and cellular homeostasis mechanisms that underlie normal and aberrant neuronal behavior, particularly focusing on how variations in external stimulation can transition a neuron into seizure-like activities. This is achieved through detailed subcellular modeling of ion channels, receptors, and ionic gradients, which are central to neuronal excitability and network dynamics.