Optimization of an anatomically and electrically detailed rodent subthalamic nucleus neuron model

• Published in: Journal of neurophysiology 2024-06, Vol.132 (1), p.136-146
• Main Authors: Chen, Hengji, Noor, M Sohail, Bingham, Clayton S, McIntyre, Cameron C
• Format: Article
• Language: English
• ISSN: 0022-3077; 1522-1598; 1522-1598
• DOI: 10.1152/jn.00287.2023

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease, but its mechanisms of action remain unclear. Detailed multi-compartment computational models of STN neurons are often used to study how DBS electric fields modulate the neurons. However, currently available STN neuron models have some limitations in their biophysical realism. In turn, the goal of this study was to update a detailed rodent STN neuron model originally developed by Gillies & Willshaw [2006]. Our design requirements consisted of explicitly representing an axon connected to the neuron and updating the ion channel distributions based on the experimental literature to match established electrophysiological features of rodent STN neurons. We found that adding an axon to the STN neuron model substantially altered its firing characteristics. We then used a genetic algorithm to optimize the biophysical parameters of the model. The optimized model exhibited spontaneous firing, action potential shape, hyperpolarization response, and frequency-current curve that aligned well with experimental recordings from STN neurons. Subsequently, we evaluated the general compatibility of the updated biophysics by applying them to 26 different STN neuron morphologies derived from 3D anatomical reconstructions. The different morphologies affected the firing behavior of the model, but the updated biophysics were robustly capable of maintaining the desired electrophysiological features. The new STN neuron model developed in this work offers a valuable tool for studying STN neuron firing properties, and may find application in simulating STN local field potentials or analysis of the effects of STN DBS.