The brain's response to an essential amino acid-deficient diet and the circuitous route to a better meal

The essential (indispensable) amino acids (IAA) are neither synthesized nor stored in metazoans, yet they are the building blocks of protein. Survival depends on availability of these protein precursors, which must be obtained in the diet; it follows that food selection is critical for IAA homeostasis. If even one of the IAA is depleted, its tRNA becomes quickly deacylated and the levels of charged tRNA fall, leading to disruption of global protein synthesis. As they have priority in the diet, second only to energy, the missing IAA must be restored promptly or protein catabolism ensues. Animals detect and reject an IAA-deficient meal in 20 min, but how? Here, we review the molecular basis for sensing IAA depletion and repletion in the brain's IAA chemosensor, the anterior piriform cortex (APC). As animals stop eating an IAA-deficient meal, they display foraging and altered choice behaviors, to improve their chances of encountering a better food. Within 2 h, sensory cues are associated with IAA depletion or repletion, leading to learned aversions and preferences that support better food selection. We show neural projections from the APC to appetitive and consummatory motor control centers, and to hedonic, motivational brain areas that reinforce these adaptive behaviors.