Kothare, M. V. | Search bioRxiv

bioRxiv2025

A Compartmental Model for Simulating the Gut-Brain Axis in Gastric Function Regulation

Gastric function is regulated by the gut-brain axis, which integrates vagal and enteric nervous system (ENS) pathways. The parasympathetic circuit within the vagal pathway promotes digestion by stimulating peristaltic activity and relaxing the Pyloric sphincter (PS) through motor and sensory neurons. In contrast, the sympathetic pathway inhibits digestion by suppressing peristalsis and constricting the PS, highlighting the complex neural coordination involved in gastric regulation. This study introduces a novel mathematical model of the gut-brain axis using a computationally efficient compartmental framework. The model simulates the vagal and ENS pathways and their corresponding effects on gastric function to improve our understanding of gut-brain axis regulation. The model employs the Michaelis-Menten equation with a Hill coefficient (MMEHC) equation to capture neurotransmitter release at neuromuscular junctions by stimulation of motor neurons and its effects on gastric cells. Motor (efferent) neurons are modeled for three key stomach regions: the fundus (tonic activity), antrum (phasic activity), and PS (both tonic and phasic activity). Thus, the stomach is represented as a three-compartment model. The stomach model extends our previous work (Fernandes et al., 2024) by incorporating passive stress and dynamic changes in stomach geometry. Sensory (afferent) inputs are represented through linear equations that account for chemo- and mechanoreceptor activity, while a binary variable captures the sympathetic response. Afferent and efferent firing rates are linked via fitted curves to effectively close the gut-brain axis feedback loop, borrowing from a similar approach used to model cardiovascular regulation. The simulation results align with physiological observations, demonstrating inhibitory digestive activity during sympathetic responses and excitatory activity, such as gastric emptying, during parasympathetic responses. During gastric emptying, the Interstitial Cells of Cajal (ICC) activity shows constant amplitude for low to medium gastric volumes but exhibits an increase in amplitude at very high gastric volumes. Furthermore, gastric emptying rates decrease with high-calorie liquids due to PS regulation, validating the potential of the model for studying Gastrointestinal (GI) disorders and developing vagal-based therapies.

biophysics↗

bioRxiv2022

Controlling Neocortical Epileptic Seizures using Forced TemporalSpike-Time Stimulation: An In Silico Computational Study

Epileptic seizure is typically characterized by highly synchronized episodes of neural activity. Existing stimulation therapies focus purely on suppressing the pathologically synchronized neuronal firing patterns during the ictal (seizure) period. While these strategies are effective in suppressing seizures when they occur, they fail to prevent the re-emergence of seizures once the stimulation is turned off. Previously, we developed a novel neurostimulation motif, which we refer to as "Forced Temporal Spike-Time Stimulation" (FTSTS) [1] that has shown remarkable promise in long-lasting desynchronization of excessively synchronized neuronal firing patterns by harnessing synaptic plasticity. In this paper, we build upon this prior work [1] by optimizing the parameters of the FTSTS protocol in order to efficiently desynchronize the pathologically synchronous neuronal firing patterns that occur during epileptic seizures using a recently published computational model of neocortical-onset seizures [2]. We show that the FTSTS protocol applied during the ictal period can modify the excitatory-to-inhibitory synaptic weight in order to effectively desynchronize the pathological neuronal firing patterns even after the ictal period. Our investigation opens the door to a possible new neurostimulation therapy for epilepsy.

neuroscience↗