Agent-based modeling of the central amygdala and pain using cell-type specific physiological parameters

DOI

10.1371/journal.pcbi.1009097

Authors

Rachael Miller Neilan, Department of Mathematics and Computer Science, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
Gabrielle Majetic, Department of Mathematics and Computer Science, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
Mauricio Gil-Silva, Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, Texas, United States of America.
Anisha P. Adke, National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, Maryland, United States of America.
Yarimar Carrasquillo, National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, Maryland, United States of America.
Benedict J. Kolber, Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, Texas, United States of America.

Document Type

Journal Article

Publication Date

6-1-2021

Publication Title

PLoS computational biology

Volume

17

Issue

6

Abstract

The amygdala is a brain area involved in emotional regulation and pain. Over the course of the last 20 years, multiple researchers have studied sensory and motor connections within the amygdala in trying to understand the ultimate role of this structure in pain perception and descending control of pain. A number of investigators have been using cell-type specific manipulations to probe the underlying circuitry of the amygdala. As data have accumulated in this research space, we recognized a critical need for a single framework to integrate these data and evaluate emergent system-level responses. In this manuscript, we present an agent-based computational model of two distinct inhibitory neuron populations in the amygdala, those that express protein kinase C delta (PKCδ) and those that express somatostatin (SOM). We utilized a network of neural links to simulate connectivity and the transmission of inhibitory signals between neurons. Type-specific parameters describing the response of these neurons to noxious stimuli were estimated from published physiological and immunological data as well as our own wet-lab experiments. The model outputs an abstract measure of pain, which is calculated in terms of the cumulative pro-nociceptive and anti-nociceptive activity across neurons in both hemispheres of the amygdala. Results demonstrate the ability of the model to produce changes in pain that are consistent with published studies and highlight the importance of several model parameters. In particular, we found that the relative proportion of PKCδ and SOM neurons within each hemisphere is a key parameter in predicting pain and we explored model predictions for three possible values of this parameter. We compared model predictions of pain to data from our earlier behavioral studies and found areas of similarity as well as distinctions between the data sets. These differences, in particular, suggest a number of wet-lab experiments that could be done in the future.

Open Access

Gold

Repository Citation

Miller Neilan, R., Majetic, G., Gil-Silva, M., Adke, A. P., Carrasquillo, Y., & Kolber, B. J. (2021). Agent-based modeling of the central amygdala and pain using cell-type specific physiological parameters. PLoS computational biology, 17 (6). https://doi.org/10.1371/journal.pcbi.1009097