Noradrenergic modulation of cortical taste processing

About This Grant

PROJECT SUMMARY Neuromodulators play a critical role in adaptively regulating sensory neural computations, yet their effects on the taste system remain poorly understood. The gustatory cortex (GC), a subregion of the insular cortex, receives a prominent modulatory input from norepinephrine (NE)-producing neurons in the locus coeruleus (LC). Despite this anatomical connection, the functional role of the LC-GC pathway has not been investigated. Our long-term goal is to understand how LC-NE dynamics influence taste perception by modulating taste encoding in the GC. Previous research in rodents has shown that GC ensemble activity encodes taste identity and palatability in a sequential manner within approximately 2.5 seconds of taste reception. Building on these findings, we hypothesize that the timing of LC-NE activation relative to tastant reception significantly shapes its effects on the encoding of taste identity and palatability. To test this hypothesis, we propose three synergistic research aims. In Aim 1, we will characterize the patterns of LC-NE activity in the context of tasting. We will examine how these patterns are influenced by taste valence, expectedness, and the acquisition of cue-taste associations. Specifically, using fiber photometry, we will monitor LC calcium dynamics and NE release in the GC as mice anticipate and sample intraorally delivered tastants. In Aim 2, we will determine the causal impact of LC-NE activity on GC taste encoding by manipulating LC output with temporal precision. We will use optogenetic tools to activate or inhibit LC axons in the GC, in combination with miniscope calcium imaging. This will allow us to assess how the timing of LC input influences GC neuronal responses and the ensemble representation of taste identity and palatability. In Aim 3, we will investigate the role of the LC-GC pathway in shaping taste-guided behaviors. We will assess taste discrimination using a two-alternative choice task and measuring taste palatability perception through licking behavior and orofacial responses. Together, these studies will provide a comprehensive understanding of how behavioral demands modulate LC activity to shape taste encoding and perception. The insights gained may advance our understanding of the neural regulation of adaptive and maladaptive consummatory behaviors.