Multimodal Gastrointestinal Neurotechnology to Investigate the Gut's Autonomic Nervous System in Freely Behaving Rodents
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mondal-rajib-phd-hst-2026-thesis.pdf
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Author(s)
Mondal, Rajib
Advisor(s)
Anikeeva, Polina
Date Issued
May 2026
Publisher
Massachusetts Institute of Technology
Abstract
The gastrointestinal autonomic nervous system (giANS) — comprising the enteric nervous system (ENS) and the gut-innervating branches of the parasympathetic and sympathetic nervous systems — forms a continuous bidirectional communication axis between the gastrointestinal (GI) tract and the central nervous system (CNS). Through this axis, the giANS coordinates local organ function, while simultaneously transmitting visceral sensory signals that modulate higher-order behavior and emotional state. Dysregulation of this system has been implicated in a wide range of conditions spanning metabolic, affective, and gastrointestinal domains. However, the mechanistic understanding of the relationship between the giANS, behavior, and pathology remains very limited. This is in part due to a lack in experimental tools capable of recording and modulating gastrointestinal activity in freely moving rodents with cellular specificity, and high spatiotemporal resolution. Existing approaches for studying the giANS in rodent models either lack specificity or are incompatible with behavior. This thesis addresses that gap through the development and in vivo validation of two complementary implantable neurotechnological platforms. The first is a multifunctional bioelectronic implant designed for chronic implantation to the gastric serosa with optogenetic stimulation and electrophysiological recording capabilities. The platform is deployed to characterize how gastric myoelectrical activity evolves across different feeding states, and to causally investigate whether optogenetic activation of gastric vagal sensory terminals is sufficient to suppress food intake. The second platform addresses the ENS directly, establishing a methodological framework for direct electrophysiological recordings of enteric neuron activity at single-unit resolution in freely behaving mice. This is achieved through an ultrathin, double-sided microelectrode array implanted into the delicate gastrointestinal wall, capable of capturing both electrically evoked and spontaneous enteric neural signals. Together, these platforms establish an experimental framework for using implantable bioelectronics to enable mechanistic studies in gut–brain research.
MIT Department
Harvard-MIT Program in Health Sciences and Technology
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