## Biological Basis of the Computational Model This code simulates the dynamics of medium spiny neurons (MSNs) in the striatum, focusing on the differential responses of D1-type and D2-type dopamine receptor-expressing neurons. MSNs are the principal neurons of the striatum and play a critical role in motor control and reward-related learning. ### Neuron Types and Libraries - **D1 MSNs**: These neurons express D1 dopamine receptors, which are typically associated with the direct pathway of the basal ganglia, facilitating movement. - **D2 MSNs**: These neurons express D2 dopamine receptors and are part of the indirect pathway, generally inhibiting movement. The code uses two separate libraries, `D1_71bestFit_updRheob.pkl` and `D2_34bestFit_updRheob.pkl`, likely containing optimized model parameters for simulating each type of MSN. ### Model Components and Parameters - **Synapses and Stimulation**: The code suggests simulating synaptic activity on dendrites and spines, as noted in the `insert_spines` and `insert_synapses` methods. This reflects the biological reality where synaptic inputs largely arrive at the dendritic spines. - **Spillover Experiment**: The term "spillover" might refer to the phenomenon where neurotransmitter release can activate not only the synapse it was released from but also neighboring synapses. This is particularly relevant in the modeling of glutamate dynamics impacting NMDA receptor activation. ### Dendritic Structure - **Dendrites and Spines**: The code manipulates dendritic segments and introduces spines, reflecting the anatomical features of MSNs with their highly branched dendritic trees and numerous spines. This enhances the neuron's capacity to integrate synaptic inputs, crucially affecting neuronal computations related to the integration of synaptic signals. ### Key Ionic and Synaptic Mechanisms - **Voltage Recordings**: Membrane potentials (`Vs`, `Vd`, `Vspine`) are recorded to understand the electrical activity of the soma, dendrites, and spines, respectively. This captures how synaptic inputs affect the neuron’s electrical state. - **NMDA Receptor Dynamics**: Although not explicitly mentioned, references to synapse insertion and spillover experiments imply a focus on NMDA receptor-mediated currents, which are vital for synaptic plasticity and excitatory transmission in MSNs. ### Synaptic Clusters and Plasticity - **Plateau Clusters**: The concept of `plateau_cluster_list` and `plateau_cluster_size` might relate to the arrangement of synaptic inputs into clusters, which can lead to sustained depolarization (plateau potentials) and are believed to be critical in synaptic plasticity mechanisms such as long-term potentiation (LTP). ### Biological Relevance Through the integration of synaptic, dendritic, and ionic dynamics, the model provides a detailed representation of how MSNs process and integrate neural signals. This has significant implications for understanding motor control, learning, and disorders such as Parkinson’s disease, where basal ganglia circuitry including the MSNs is affected. Overall, the model seeks to explore synaptic integration and plasticity in MSNs, allowing for insights into the physiological and pathophysiological processes underlying striatal function and dysfunction.