GABAA and GABAB receptors in the anterior piriform cortex modulate feeding in rats

Truong, Ban G; Magrum, Linda J.; Gietzen, Dorothy W.

doi:10.1016/s0006-8993(01)03213-9

Cited by 22 publications

(19 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, our BRET analysis demonstrates that ATF4 and GABA(B)R1 directly interact in living cells. These data are supported by observations made in rodents indicating that suppression of GABAergic inhibition contributes to EAAD-induced food avoidance (Truong et al, 2002). We therefore propose a model whereby, in response to EAAD, activation of dGCN2 induces dATF4-mediated GABA signaling inhibition, dopamine release, and food rejection ( Figure 6D).…”

Section: Discussionsupporting

confidence: 87%

Sensing of Amino Acids in a Dopaminergic Circuitry Promotes Rejection of an Incomplete Diet in Drosophila

Bjordal¹,

Arquier²,

Kniazeff³

et al. 2014

Cell

137

135

View full text Add to dashboard Cite

The brain is the central organizer of food intake, matching the quality and quantity of the food sources with organismal needs. To ensure appropriate amino acid balance, many species reject a diet lacking one or several essential amino acids (EAAs) and seek out a better food source. Here, we show that, in Drosophila larvae, this behavior relies on innate sensing of amino acids in dopaminergic (DA) neurons of the brain. We demonstrate that the amino acid sensor GCN2 acts upstream of GABA signaling in DA neurons to promote avoidance of the EAA-deficient diet. Using real-time calcium imaging in larval brains, we show that amino acid imbalance induces a rapid and reversible activation of three DA neurons that are necessary and sufficient for food rejection. Taken together, these data identify a central amino-acid-sensing mechanism operating in specific DA neurons and controlling food intake.

show abstract

Section: Discussionsupporting

confidence: 87%

Sensing of Amino Acids in a Dopaminergic Circuitry Promotes Rejection of an Incomplete Diet in Drosophila

Bjordal¹,

Arquier²,

Kniazeff³

et al. 2014

Cell

137

135

View full text Add to dashboard Cite

show abstract

“…Excess GABA in the anterior piriform cortex region reduces feeding (Truong et al, 2002). We believe that the reduced body weight and tremor is not related to delayed (or retarded) development, because mGAT1 KO mice are reproductive at the same time as WT and display muscle strength and balance similar to WT.…”

Section: Reduced Body Weightmentioning

confidence: 88%

GABA Transporter Deficiency Causes Tremor, Ataxia, Nervousness, and Increased GABA-Induced Tonic Conductance in Cerebellum

Chiu

Brickley²,

Jensen³

et al. 2005

J. Neurosci.

218

170

View full text Add to dashboard Cite

GABA transporter subtype 1 (GAT1) knock-out (KO) mice display normal reproduction and life span but have reduced body weight (female, Ϫ10%; male, Ϫ20%) and higher body temperature fluctuations in the 0.2-1.5/h frequency range. Mouse GAT1 (mGAT1) KO mice exhibit motor disorders, including gait abnormality, constant 25-32 Hz tremor, which is aggravated by flunitrazepam, reduced rotarod performance, and reduced locomotor activity in the home cage. Open-field tests show delayed exploratory activity, reduced rearing, and reduced visits to the central area, with no change in the total distance traveled. The mGAT1 KO mice display no difference in acoustic startle response but exhibit a deficiency in prepulse inhibition. These open-field and prepulse inhibition results suggest that the mGAT1 KO mice display mild anxiety or nervousness. The compromised GABA uptake in mGAT1 KO mice results in an increased GABA A receptor-mediated tonic conductance in both cerebellar granule and Purkinje cells. The reduced rate of GABA clearance from the synaptic cleft is probably responsible for the slower decay of spontaneous IPSCs in cerebellar granule cells. There is little or no compensatory change in other proteins or structures related to GABA transmission in the mGAT1 KO mice, including GAT1-independent GABA uptake, number of GABAergic interneurons, and GABA A -, vesicular GABA transporter-, GAD65-, and GAT3-immunoreactive structures in cerebellum or hippocampus. Therefore, the excessive extracellular GABA present in mGAT1 KO mice results in behaviors that partially phenocopy the clinical side effects of tiagabine, suggesting that these side effects are inherent to a therapeutic strategy that targets the widely expressed GAT1 transporter system.

show abstract

“…It is clear that the highly sensitive APC is activated by acute IAA deficiency. Given the ongoing oscillatory activity of the APC (26), the excitatory effects of signaling systems such as CaMKII (100) and ERK (97,99), and the paucity of inhibitory elements (23, 98,105), the findings reviewed here may account for the potentiation of the APC in response to IAA deficiency. Some seizure disorders seem intractable and seizure patients may have occasional unexplained breakthrough seizures.…”

Section: Iaa Deficiencymentioning

confidence: 97%

“…Gamma amino butyric acid (GABA) is the primary source of inhibitory neurotransmission in the brain (79) and is crucially important in maintaining normal levels of neuronal activity in the APC (21,22), providing damping of the recurrent excitatory circuitry. Agonists and antagonists of the GABAergic system injected into the APC of animals fed IAA-depleting diets have provided results correlating activity of the GABA system with food intake (105). This suggests that inhibitory transmission is associated with controlling the downstream effects of APC signaling, more directly involved in the food intake response, rather than with the chemosensory role of the APC.…”

Section: Intracellular Calciummentioning

confidence: 99%

Mechanisms of Food Intake Repression in Indispensable Amino Acid Deficiency

2007

View full text Add to dashboard Cite

Animals reject diets that lead to indispensable amino acid (IAA) depletion or deficiency. This behavior is adaptive, as continued IAA depletion is incompatible with maintenance of protein synthesis and survival. Following rejection of the diet, animals begin foraging for a better IAA source and develop conditioned aversions to cues associated with the deficient diet. These responses require a sensory system to detect the IAA depletion and alert the appropriate neural circuitry for the behavior. The chemosensor for IAA deprivation is in the highly excitable anterior piriform cortex (APC) of the brain. Recently, the well-conserved general AA control non-derepressing system of yeast was discovered to be activated by IAA deprivation via uncharged tRNA in mammalian APC. This system provides the sensory limb of the mechanism for recognition of IAA depletion that leads to activation of the APC, diet rejection, and subsequent adaptive strategies.

show abstract

GABAA and GABAB receptors in the anterior piriform cortex modulate feeding in rats

Cited by 22 publications

References 27 publications

Sensing of Amino Acids in a Dopaminergic Circuitry Promotes Rejection of an Incomplete Diet in Drosophila

Sensing of Amino Acids in a Dopaminergic Circuitry Promotes Rejection of an Incomplete Diet in Drosophila

GABA Transporter Deficiency Causes Tremor, Ataxia, Nervousness, and Increased GABA-Induced Tonic Conductance in Cerebellum

Mechanisms of Food Intake Repression in Indispensable Amino Acid Deficiency

Contact Info

Product

Resources

About