Fellowship for Joshua Kogan: The Role of Gustatory Cortex in Perceptual Learning of Taste

PROJECT SUMMARY To adapt and survive in natural environments, animals need to learn to discriminate sensory stimuli predicting different outcomes. This ability is particularly important in the case of largely overlapping sensory inputs. For example, in taste, small differences between otherwise similar solutions could mean the difference between ingesting a poison and having a safe meal. This phenomenon, known as perceptual learning, has been well documented across species and sensory modalities. However, understanding the mechanisms of neural plas- ticity underlying perceptual learning - i.e. how the brain plastically encodes, generalizes and discriminates large numbers of overlapping stimuli - remains a great challenge in neuroscientific research. Studies in the visual and auditory systems have converged on two non-mutually exclusive models, 1) enhancement of sensory represen- tations and 2) improved ability of decision-making circuits to interpret sensory evidence to guide actions. Gener- ally, these two types of activity are found in different brain areas, however both types can be found in the primary taste cortex, known as the gustatory insular cortex (GC). This makes taste an ideal system to test relative con- tributions of the two models. Additionally, the mechanisms of plasticity underlying perceptual learning remain incompletely understood, but some studies have suggested a role for the neuromodulator, dopamine. The cur- rent proposal will test the hypotheses that 1) representations of overlapping taste stimuli and associated deci- sions by GC neurons separate as mice learn a perceptual discrimination task; 2) GC DAergic signaling mediates plasticity underlying task learning and performance. I will rely on a taste-based two alternative forced choice (2AFC) in which mice are trained to detect the predominant taste in a mixture. To study chemosensory and decision-related coding in GC, I will use chronic 2-photon and widefield calcium imaging in populations of GC neurons as mice learn. To parse the role of dopamine in task learning and performance, I will use selective lesioning of GC dopaminergic axons and local chemogenetic inhibition of dopamine transmission combined with calcium imaging. These experiments will provide important information about taste processing, the neural basis of perceptual learning and the role of cortical dopamine in taste and sensory processing more broadly.