Molecular Neurobiology

, Volume 46, Issue 2, pp 332–348

The Brain's Response to an Essential Amino Acid-Deficient Diet and the Circuitous Route to a Better Meal

Article

DOI: 10.1007/s12035-012-8283-8

Cite this article as:
Gietzen, D.W. & Aja, S.M. Mol Neurobiol (2012) 46: 332. doi:10.1007/s12035-012-8283-8

Abstract

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.

Keywords

Nutrient sensingAnterior piriform cortexHypothalamusFeeding circuitsEssential amino acidsForagingLearned aversionLearned preferenceGCN2

Abbreviations

AGm

Medial agranular (supplementary motor) cortex

AMYG

Amygdala

AP

Area postrema

APC

Anterior piriform cortex

ATF

Activating transcription factor

BG

Basal ganglia

BL

Basolateral

CaSR

Calcium sensing receptor

CaMKII

Calcium calmodulin kinase II

Ce

Central

CTA

Conditioned taste aversion

CVO

Circumventricular organ

Cx

Cortex

DA

Dopamine

D1or 2

Dopamine receptor categories 1or 2

DLLH

Dorsolateral perifornical lateral hypothalamus

DMH

Dorsomedial hypothalamus

eIF2

Eukaryotic initiation factor 2

ERK

Extracellular signal-related kinase

GCN2

General amino acid control non-derepressing kinase 2

GP

Globus pallidus

GluR1

Glutamate receptor 1

HIP

Hippocampus

HRP

Horseradish peroxidase

IAA

Indispensable (essential in the diet) amino acid

IC

Insular (taste) cortex

icv

Intracerebroventricular

LH

Lateral hypothalamic area

MAPK

Mitogen-activated protein kinase

MeAIB

2-Methylamino isobutyric acid

mTOR

Mammalian target of rapamycin

NAcc

Nucleus accumbens

NE

Norepinephrine

NTS

Nucleus of the tractus solitarius

OFC

Orbitofrontal cortex

PBN

Parabrachial nucleus

PVN

Paraventricular nucleus of the hypothalamus

PI3kinase

Phosphatidylinositol 3 kinase

PFC

Prefrontal cortex

RT

Reticular thalamus

SCAA

Sulfur-containing amino acid

SNAT

Sodium-coupled neutral amino acid transporter

STR

Striatum (caudate + putamen)

tRNA

Transfer ribonucleic acid

vent TEG

Ventral tegmentum

VMH

Ventromedial hypothalamus

VP

Ventral pallidum

ZI

Zona incerta

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Anatomy, Physiology and Cell Biology, School of Veterinary MedicineUniversity of California, DavisDavisUSA
  2. 2.Department of NeuroscienceJohns Hopkins University School of MedicineBaltimoreUSA