P033 Modeling Corticospinal Input Effects on V1-FoxP2 Interneurons in a Go Task Using NetPyNE

Andres F. Cadena Parra1*, Michelle Sanchez Rivera3, Constantinos Eleftheriou3, Roman Baravalle2, Ian Duguid3, Salvador Dura-Bernal2,4
1Department of Biomedical Engineering. Universidad de los Andes, Bogota, Colombia
2Department of Physiology and Pharmacology, SUNY Downstate Health Sciences University, Brooklyn, USA
3Centre for Discovery Brain Sciences & Simons Initiative for the Developing Brain, University of Edinburgh, Edinburgh, UK.
4Center for Biomedical Imaging & Neuromodulation, The Nathan Kline Institute for Psychiatric Research.


*Email: af.cadena@uniandes.edu.co
Introduction

The execution of movement involves a complex interplay of neural structures whose activity results in precise motor output. The motor cortex generates commands for voluntary movement, conveyed via corticospinal neurons (CSNs) to the spinal cord, where interneurons (INs) integrate sensory feedback and motor commands to fine-tune motor neuron activity [1]. Among these V1 INs, and particularly those expressing FoxP2, are crucial for inhibitory feedback in motor control [2]. Building on recent findings that a subset of CSNs exhibit decreased firing rates during movement, this study aims to investigate how these CSN inputs influence V1-FoxP2 interneurons, shedding light on spinal integration mechanisms for coordinated motor output.
Methods
An in silico model was developed to study the effects of convergent increased/decreased corticospinal input on V1-FoxP2 INs. A single-cell model was implemented in NetPyNE/NEURON, incorporating Na⁺, K⁺, Ca²⁺ channels and AMPA dynamics. The cell’s morphology had a soma and four dendritic sections. Calibration used in vitro current-clamp data and optimization. Spike trains from a “Go task” from two different CSN subpopulations were connected to the V1-FoxP2 model, with simulated background activity consistent with in vivo observations [3]. Three conditions were tested: (1) increasing/decreasing input, (2) increasing/sustained input, and (3) increasing input only. Electrophysiological properties, like input resistance, were recorded over time.
Results
The model simulated in vivo V1-FoxP2 dynamics, where corticospinal input initially drives an increase in firing rate that peaks at movement onset, followed by a return to baseline. The in vivo condition optimizes the input-output relationship, exhibiting a high signal-to-noise ratio (SNR) post-movement and enabling a quicker return to baseline excitability. Additionally, background activity enhances the return to baseline of the V1-FoxP2 firing rate and input resistance. Notably, input resistance decreased progressively across time windows before, during, and after movement, making the neuron less susceptible to noise. The model further revealed that movement requires a specific ratio of increased and decreased CSN inputs.
Discussion
Our findings provide key insights into the neuronal computations that govern the integration of cortical inputs in the spinal cord. The model showed that in vivo-like corticospinal input enhances V1-FoxP2 activity time-locking to behavior without significantly reducing the SNR. This indicates a trade-off between temporal precision and firing rate strength to optimize motor control. Additionally, decreasing CSN input facilitates impedance recovery after movement, whereas in the sustained scenario, impedance fails to return to baseline. These results may inform future studies on the functional architecture of spinal circuits involved in motor control and rehabilitation, particularly in disorders affecting motor coordination.



Acknowledgements
This work was supported by the NIBIB U24EB028998 and NYS DOH01-C32250GG-3450000 grants. AFCP was supported by Universidad de los Andes through a Teaching Assistantship.
References
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