CGRP neurons and the neural circuitry underlying conditioned taste aversion

Thesis (Ph.D.)--University of Washington, 2019Food aversions develop when the taste of a novel food is associated with sickness, which often occurs after food poisoning or chemotherapy treatment. This phenomenon, known as conditioned taste aversion (CTA), protects animals against repeated self-administration of potentially toxic foods. Despite its importance as a basic survival mechanism, the neural basis of CTA is poorly understood. In order to form a CTA, it is postulated that taste and malaise information converge which results in formation of a long-term memory. A population of neurons in the hindbrain that express calcitonin gene-related peptide (CGRP) has been shown to mediate malaise. Pairing a novel food with activation of CGRP neurons in the parabrachial nucleus (PBN) is sufficient to establish a CTA. Additionally, silencing CGRP neurons can abolish CTA learning. The purpose of this thesis is to delineate the role of CGRP neurons and their downstream projections in the acquisition and expression of CTA. Using in vivo calcium imaging, we show that CGRP neurons are reactivated by the conditioned taste following CTA. Additionally, CGRP neurons undergo plasticity following CTA and inactivation of genes involved in memory consolidation prevents establishment of a strong CTA. Photoactivation of projections from CGRP neurons in either the central nucleus of the amygdala (CeA) or the bed nucleus of the stria terminalis (BNST) can also induce robust CTA. Activation of CGRP receptor-expressing neurons in the CeA is sufficient to suppress feeding but it does not result in a CTA. Together, these findings show that CGRP neurons not only play a key role for learning food aversions and also contribute to the maintenance and expression of these memories. Future studies that identify additional gene markers in the CeA and BNST will further our understanding of downstream neurons involved in CTA