Subcellular and mesoscale circuit organization for taste and visceral processing

Interoception, the neural representation of the body’s internal state, is critical to health and survival. Despite its importance for animal wellbeing, the precise central circuit mediating interoception remains largely unknown. The insular cortex, a key hub for interoception, is known to integrate external and internal sensory signals with higher order processes. However, while the circuits driving external (e.g. auditory, visual, somatic) sensory pro- cessing are extensively studied, those for internal sensations and which mediate their integration in the insula remain largely elusive. Thus, our lacking knowledge of the central substrates that convey internal sensations has delimited our understanding of and therapeutic advancement for interoceptive disease states, like anorexia and anxiety. To this end, this proposal aims to uncover the subcellular and mesoscale circuit organizations for taste and visceral sensory integration and link these two internal sensory circuits to their behavioral functions. First, I will determine how taste-sensing neurons of the parvicellular ventroposterior medial thalamus (VPMpc) and visceral-relay neurons of the external lateral parabrachial nucleus (PBNel) organize their synaptic inputs across the dendritic subdomains of pyramidal neurons within the posterior insula. Then, I will assess the ne- cessity of the PBNel-to-insula circuit in conditioned taste aversion, an interoceptive behavior. Finally, I will iden- tify the input brain regions that drive two insula-converging neuronal populations to determine the broader cir- cuit architecture for internal sensory processing. My central hypothesis is that distinct subcellular and mesoscale circuit architectures through the VPMpc and PBNel subserve taste-visceral integration within the insula and drive aversion behavior. To test this hypothesis, I will learn subcellular channelrhodopsin-assisted circuit mapping and whole cell patch clamp electrophysiology to compare the functional synaptic organizations of VPMpc or PBNel inputs onto insular pyramidal neurons. I will then use circuit-specific ablation of synaptic transmission with tetanus toxin to evaluate the role of insula-projecting PBNel neurons in conditioned taste aversion. Finally, I will learn pseudotyped rabies-mediated viral tracing to label upstream populations impinging on VPMpc-to-insula and PBNel-to-insula circuits, thus elucidating polysynaptic architectures for internal sen- sory systems in the brain. Achieving these aims will provide novel insight into how insular neurons receive and integrate taste and visceral information to affect behavior, and lay the foundation for future investigation into the central interoceptive system. This project will complement a comprehensive training plan that I have devel- oped with my mentor, Dr. Tianyi Mao. In addition to advanced training in technical methodology, I will enhance my skills in programming, experimental design, and quantitative analysis. I will also deepen my understanding of central sensory processing and interoception research. Finally, I expect to engage in activities that will de- velop my skills in scientific communication. The proposed training will position me to succeed as an independ- ent researcher and leader in academic research. Project Number: 1F31NS143300-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Kayla Maanum | Institution: OREGON HEALTH & SCIENCE UNIVERSITY, PORTLAND, OR | Award Amount: $50,114 | Activity Code: F31 | Study Section: Special Emphasis Panel[ZRG1 F02B-H (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11388200