MEMP PhD Thesis Defense: Rajib Mondal

Gastrointestinal neurotechnology to study the autonomic nervous system of the gut in freely behaving rodents

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. Tho work presented addresses this 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 and causal inference in gut–brain research.  

Thesis Supervisor:
Polina Anikeeva, PhD
Matoula S. Salapatas Professor of Materials Science and Engineering, MIT
Professor, Department of Brain and Cognitive Sciences, MIT

Thesis Committee Chair:
Alan Jasanoff, PhD
Eugene McDermott Professor in the Brain Sciences and Human Behavior, Department of Biological Engineering, MIT

Thesis Readers:
Lauren Orefice, PhD
Assistant Professor, Department of Molecular Biology, Massachusetts General Hospital
Assistant Professor, Department of Genetics, Harvard Medical School

Robert Langer, ScD
David H. Koch Institute Professor, Departments of Chemical Engineering and Biological Engineering, MIT
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Topic: Rajib Mondal MEMP PhD Thesis Defense
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