Cortical circuits and neurotransmitters for taste aversion learning

Summary Taste perception is a complex process that includes the chemosensory detection of a stimulus and information regarding its valence - whether a stimulus is pleasant or aversive. The gustatory cortex is a central component of the taste system and is involved in taste learning as well as decisions to ingest or reject a food. Thus, it is a central component of the neural circuit involved in the assignment of a valence to a taste stimulus. To date, much of the work on understanding how taste valence is encoded focused on the analysis of limbic inputs to the gustatory cortex. This work has substantially advanced our understanding of the network taste perception and learning but has not resolved the circuit mechanisms regulating taste valence. In this proposal, we take advantage of a well-established form of taste aversion learning to modulate taste hedonic value and analyze the contribution of neuronal and circuits mechanisms for the coding of valence. The multi-level approach we have designed will bring together analysis of neuromodulatory signals on specific groups of cortical neurons and on cortical circuits with in vivo imaging in awake mice to determine how valence is encoded. We will also use selective manipulations of the expression of specific receptors and analysis of behavior to bring into focus the role of specific neuronal signals in the formation and expression of taste valence memories. The implications of the proposed work for public health are substantial. Changes in taste valence may emerge as a side effect of cancer treatment or be associated with gastrointestinal disorders, preventing patients from enjoying food and ingesting the calories they need to support their recovery. Furthermore, many neurological and psychiatric disorders are associated with altered sensory perception, or with anhedonia, the loss of pleasure associated with sensory experiences. The circuits for taste perception in human and rodents are quite conserved and both species rely on valence to make decisions about food choices, providing a unique opportunity for investigating common mechanism of sensory processing, as well as for the study of the circuit underpinning for the association of sensory stimuli with their hedonic value. The focus of the proposed work on specific signaling mechanisms and neuron types has the added potential of helping to identify novel targets for therapeutic intervention.