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

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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.

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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

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Acknowledgements

The tract-tracing work of Dr. Aja was supported by National Institutes of Health (NIH) grant DK 09271. DWG had support from NIH grants DK42274, NS 043210, and NS 33347, and from Ajinomoto Co., Inc., Tokyo. We extend particular thanks to Dr. Kunio Torii for his kind advice and collaboration. The authors are grateful to the many students and postdoctoral fellows and technicians in the Food Intake Laboratory at the University of California, Davis, who provided assistance with the animal and biochemical studies (to all those who weighed spill papers, special thanks). The authors extend our profound apologies to those whose volumes of work could not be included due to space limitations.

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  1. Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, One Shields Ave, Davis, CA, 95616, USA

    Dorothy W. Gietzen

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, 855 North Wolfe Street, Rangos 472, Baltimore, MD, 21205, USA

    Susan M. Aja

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  1. Dorothy W. Gietzen
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Correspondence to Dorothy W. Gietzen.

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Gietzen, D.W., Aja, S.M. The Brain's Response to an Essential Amino Acid-Deficient Diet and the Circuitous Route to a Better Meal. Mol Neurobiol 46, 332–348 (2012). https://doi.org/10.1007/s12035-012-8283-8

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  • DOI: https://doi.org/10.1007/s12035-012-8283-8

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