# Biological Basis of the Code The provided code is a computational neuroscience model designed to simulate essential tremor and test real-time phase-locked transcranial alternating current stimulation (tACS) as a potential intervention. Essential tremor is a neurological disorder characterized by rhythmic, involuntary movements, often in the hands. The code models specific neural circuits implicated in this disorder. ## Key Biological Elements ### Neuronal Populations 1. **Inferior Olivary Nucleus (ION):** - The ION is known for generating rhythmic oscillations and is often linked to motor control functions. In the code, 40 ION cells are stimulated to induce oscillatory behavior, mimicking tremor onset. The presence of oscillations is likely crucial for the manifestation of essential tremor. 2. **Purkinje Cells (PC):** - Purkinje cells (in the cerebellum) play a key inhibitory role in motor coordination. The code configures 200 PC cells that are consequently involved in the synaptic connections to the deep cerebellar nuclei (DCN), indicating their inhibitory role in modulating DCN output. 3. **Deep Cerebellar Nuclei (DCN):** - DCN cells receive inhibitory input from Purkinje cells and project to motor thalamus (TC). This output is crucial for sending motor information to higher brain regions. The code includes five such DCN cells for recording. 4. **Thalamocortical (TC) Cells:** - These cells are part of the Vim nucleus in the thalamus. The Vim is involved in the relay of motor and sensory information between the cerebellum and the motor cortex. Five TC cells are being used for voltage recordings here. 5. **Motor Cortex (MC) Cells:** - These cells are part of the pathway from the thalamus to the primary motor cortex, an area critically involved in voluntary movement. The synaptic interactions between simulated MC and other cells (e.g., thalamus) reflect the path for conveying movement instructions. ### Synaptic Connections - **Synaptic Pathways:** - The code establishes synaptic connections between various cell types using gap junctions and synaptic conductances, reflecting known pathways. For example, connections appear between ION and PC (inferior olive to Purkinje cells), PC to DCN (Purkinje cells to deep cerebellar nuclei), and DCN to TC (deep cerebellar nuclei to thalamus). These pathways contribute to tremor onset and the cerebellothalamocortical loop involved in motor control. ### Phase-Locked Stimulation - **Sinusoidal and phase-locked stimulation is set up for PC cells using the `SinClamp` object, presumably to mimic tACS effects. This is aimed at synchronizing the oscillatory activity, which is hypothesized to modulate or reduce tremor rhythms by realigning the abnormal network oscillations associated with essential tremor.** ### Parameters and Recordings - **Biological Parametrization:** - The synaptic parameters such as time constant (`tau`) and maximal conductance (`g`) are randomized to reflect biological variability. - **Action Potential Counting:** - The action potentials (spikes) from both PC and ION cells are recorded. This is crucial to measure neuronal excitability and oscillatory behavior, both critical metrics in the study of tremors. ### Overall Purpose The model simulates the behavior of neurons and their synaptic connections involved in the cerebellothalamocortical circuit which underlies motor control and is implicated in essential tremor. The real-time, phase-locked tACS component aims to explore therapeutic avenues by interacting with these circuits to potentially mitigate the tremor symptoms, leveraging the biological plasticity of neuronal oscillations.