# Biological Basis of the Model Code The provided code is a computational neuroscience model aimed at studying the effects of non-phase-locked transcranial alternating current stimulation (tACS) on essential tremor, a neurological disorder characterized by involuntary rhythmic muscle contractions. The approach is implemented using the NEURON simulation environment, a powerful tool for simulating individual neurons and complex neural networks. ## Key Biological Elements Modeled ### 1. **Neuronal Populations** The code models several types of neurons, each representing different brain regions involved in essential tremor: - **Inferior Olivary Nucleus (ION):** ION is involved in motor control and timing. It's simulated here with ION cells being externally stimulated to induce oscillations—a phenomenon hypothesized to trigger and sustain tremor-related activity. - **Purkinje Cells (PC):** Found in the cerebellum, these cells inhibit the deep cerebellar nuclei (DCN), playing a critical role in fine motor coordination. - **Deep Cerebellar Nuclei (DCN):** These serve as a major relay point for cerebellar output to other brain regions. In the model, they receive input from PC and influence other target neurons. - **Thalamocortical Cells (TC):** The model includes these cells to represent part of the thalamocortical network, which is involved in sensory integration and motor control. - **Motor Cortex (MC):** These cells represent the primary motor cortex, which initiates and controls voluntary muscle activity. ### 2. **Synaptic Connections** Inter-cell synaptic connections are established to mimic network interactions that occur in the actual biological systems: - PC to DCN connections represent cerebellar output modulation. - DCN to other structures emulate how cerebellar computations influence broader neural circuits, particularly those involved in motor output. ### 3. **Stimulation and Plasticity** - **SinClamp Stimulation:** Each Purkinje cell receives a sinusoidal current (SinClamp) with parameters that model non-phase-locked tACS. This stimulation mirrors therapeutic approaches intended to modulate oscillatory activity to alleviate tremors. The frequency parameter of 7 Hz corresponds to the typical tremor frequency in essential tremors. - **Adjustments via Random Number Generators:** Synaptic parameters such as tau and conductance (g) for PC to DCN synapses are adjusted using random number generators to introduce variability. This represents normal biological variation and plasticity within synapses. ### 4. **Data Recording** - Action potential counts (APCount) are recorded across various neurons (PC, DCN, TC, ION) to measure network activity and assess the impact of tACS on neural dynamics. ### 5. **Experimental Setup** - Initializes neurons to a resting membrane potential (`v_init = -57 mV`) and specifies simulation parameters that mimic physiological experiments, including setting up delays and durations that reflect synaptic transmission and neuronal response times observed in biological systems. In summary, the code is designed to simulate the network dynamics of key neuronal populations and pathways involved in essential tremor. By applying non-phase-locked tACS, the model explores therapeutic interventions aiming to disrupt or alter pathological neural oscillations characteristic of tremor conditions.