UC Davis

The gut facilitates digestion and absorption of nutrients, while the brain carries out many higher-level functions, including cognition and interaction with the peripheral nervous system. Despite the anatomical separation between the gut and the brain, there is constant communication between the two. Signals from the brain are sent to the gut to regulate digestion, while satiety signals are sent from the gut back to the brain. A healthy gut microbiome promotes homeostasis between the gut and brain, where microbiome dysbiosis can lead to an increase in intestinal epithelium permeability and leakage of microbial factors across the epithelium, all of which playing a role in diseases such as diabetes, obesity, and neuro-psychiatric conditions. There are currently no in vitro models to study this interaction between the gut and the brain. In this dissertation, we develop an in vitro model of the gut-brain axis utilizing microfluidic devices. First, we established a culture of primary rat vagal afferent neurons and satellite glial cells from adult rats. We systematically compared culture media formulations and culture surface treatments to identify culture conditions amenable for neuronal viability and function. We subsequently expose the neurons to various physiologically-relevant molecules and observe their response via live-cell imaging, as well as extracellular recordings. We then designed and fabricated microfluidic devices to physically separate the neuronal soma and nerve terminals thereby more accurately mimicking their anatomical layout. We studied how different channel geometries influence neurite growth and employed the microfluidically-separated cultures to study retrograde transport of a cholera toxin subunit and neuronal excitability from the nerve terminals. Lastly, we studied the spatiotemporal distribution of capsaicin receptor along the cultured neuron, demonstrating regenerative potential of neurites in culture. We expect that the engineered platform will serve as a versatile research tool to enable various studies involving the role of vagus nerve in the gut- brain axis.