AMPK acts as a molecular trigger to coordinate glutamatergic signals and adaptive behaviours during acute starvation.

Moloud Ahmadi,Richard Roy

doi:10.7554/elife.16349

Abstract

The stress associated with starvation is accompanied by compensatory behaviours that enhance foraging efficiency and increase the probability of encountering food. However, the molecular details of how hunger triggers changes in the activity of neural circuits to elicit these adaptive behavioural outcomes remains to be resolved. We show here that AMP-activated protein kinase (AMPK) regulates neuronal activity to elicit appropriate behavioural outcomes in response to acute starvation, and this effect is mediated by the coordinated modulation of glutamatergic inputs. AMPK targets both the AMPA-type glutamate receptor GLR-1 and the metabotropic glutamate receptor MGL-1 in one of the primary circuits that governs behavioural response to food availability in C. elegans. Overall, our study suggests that AMPK acts as a molecular trigger in the specific starvation-sensitive neurons to modulate glutamatergic inputs and to elicit adaptive behavioural outputs in response to acute starvation.

Highlights

Most organisms are faced with unpredictable fluctuations in their natural environment that often lead to periods of limited food resources
Our results indicate that AMPK acts as a starvation-inducible molecular trigger in the nervous system that modulates glutamatergic neuronal activity by at least two distinct mechanisms to modify behavioural outcomes in response to energy stress
AMPK has been implicated in the regulation of feeding behaviours in higher animals (Minokoshi et al, 2004; Yang et al, 2011) its essential role in development and cellular homeostasis has made it very difficult to study its role outside this closed circuit

Summary

Introduction

Most organisms are faced with unpredictable fluctuations in their natural environment that often lead to periods of limited food resources. The Agouti-related protein (AGRP)- and Proopiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus form a core circuit to regulate food intake and energy expenditure through the modulation of their neuronal activity in response to hormonal signals linked to metabolic status (Cowley et al, 2001; Bewick et al, 2005; Yang et al, 2011) The activity of both of these neuronal populations is mediated by engaging signalling pathways that control the strength and/or plasticity of rapid, excitatory glutamatergic transmission (Bito et al, 2010; Collingridge et al, 2010; Liu et al, 2012), but how energy stress results in changes in neuronal activity to elicit adaptive, or even compulsive behaviours are just beginning to be elucidated (Dietrich et al, 2015)

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Conclusion