Figure.

How Bitter Works: the process of bitter perception. The generation of bitter taste starts when a bitter compound enters the oral cavity, where the ligand binds to a T2R G-protein coupled receptor expressed in the apical membrane of receptor cells found in taste buds, triggering a cascade of signaling events, leading to the release of neurotransmitter that activates an afferent nerve fiber that transmits the signal via the cranial nerve to the brain. Taste buds are distributed in distinct fields in the oral, pharyngeal, and laryngeal epithelia, with each field innervated by a different cranial nerve branch. Only the taste buds on the tongue are depicted in the figure. The taste buds of the laryngeal epithelium are thought to be involved more with protection of the airways. Taste receptors have also been identified in a variety of nongustatory tissues, such as the gut, where they have been proposed to play a role in nutrient and toxin sensing. The taste signals course through the brain and provide input to circuits that subserve various functions, such as oromotor and physiological reflexes, discriminative perception, and affective processing. The figure illustrates the complexity of the mechanisms intervening between the application of the bitter stimulus and the generation of the behavioral response, providing a variety of potential targets for strategies to modulate the bitterness of medications. VPM_PC, ventral posterior medial nucleus, parvocellular subdivision. *The insula/operculum is actually lateral to the sagittal plane of section shown. Cell and molecular segment adapted from Finger and Kinnamon (2011).⁵³