Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression

Craig A Schiltz,Charles F Landry,Ann E Kelley,Quentin Z Bremer

doi:10.1186/1741-7007-5-16

Abstract

BackgroundCues predictive of food availability are powerful modulators of appetite as well as food-seeking and ingestive behaviors. The neurobiological underpinnings of these conditioned responses are not well understood. Monitoring regional immediate early gene expression is a method used to assess alterations in neuronal metabolism resulting from upstream intracellular and extracellular signaling. Furthermore, assessing the expression of multiple immediate early genes offers a window onto the possible sequelae of exposure to food cues, since the function of each gene differs. We used immediate early gene and proenkephalin expression as a means of assessing food cue-elicited regional activation and alterations in functional connectivity within the forebrain.ResultsContextual cues associated with palatable food elicited conditioned motor activation and corticosterone release in rats. This motivational state was associated with increased transcription of the activity-regulated genes homer1a, arc, zif268, ngfi-b and c-fos in corticolimbic, thalamic and hypothalamic areas and of proenkephalin within striatal regions. Furthermore, the functional connectivity elicited by food cues, as assessed by an inter-regional multigene-expression correlation method, differed substantially from that elicited by neutral cues. Specifically, food cues increased cortical engagement of the striatum, and within the nucleus accumbens, shifted correlations away from the shell towards the core. Exposure to the food-associated context also induced correlated gene expression between corticostriatal networks and the basolateral amygdala, an area critical for learning and responding to the incentive value of sensory stimuli. This increased corticostriatal-amygdalar functional connectivity was absent in the control group exposed to innocuous cues.ConclusionThe results implicate correlated activity between the cortex and the striatum, especially the nucleus accumbens core and the basolateral amygdala, in the generation of a conditioned motivated state that may promote excessive food intake. The upregulation of a number of genes in unique patterns within corticostriatal, thalamic, and hypothalamic networks suggests that food cues are capable of powerfully altering neuronal processing in areas mediating the integration of emotion, cognition, arousal, and the regulation of energy balance. As many of these genes play a role in plasticity, their upregulation within these circuits may also indicate the neuroanatomic and transcriptional correlates of extinction learning.

Highlights

Cues predictive of food availability are powerful modulators of appetite as well as foodseeking and ingestive behaviors
We have demonstrated that conditioned locomotor arousal is not sufficient to elicit the pattern of gene expression observed here and that increased gene expression, for example in the prefrontal cortex, is not necessary for locomotor arousal [49,50,51]
Using a novel application of statistical methods, we found that cues associated with palatable food produced dramatic changes in the functional connectivity of circuits that are known to modulate adaptive behavior

Summary

Introduction

Cues predictive of food availability are powerful modulators of appetite as well as foodseeking and ingestive behaviors. Consumption of a mere 50–100 extra kilocalories without compensatory expenditure has been proposed to be a main cause of the increasing incidence of overweight and obesity [1,2] As this trend has been occurring over the past 25 years, environmental factors such as increased food availability and the power of sensory food-associated sensory cues in the modern environment (e.g. advertising) may be responsible for the initiation and maintenance of increased energy intake [3]. Presentation of cues associated with preferred versus non-preferred foods increases activity in cortical areas and the amygdala [10,14,15], and images of highcalorie versus low-calorie foods activate regions of the cortex and the thalamus [16,17] Overall, these studies demonstrate that food preference, caloric density, and shortterm energy balance can influence regional neuronal activity and food intake resulting from exposure to foodrelated stimuli. Stress can increase selfreported liking and overall intake of food, yet the neuroanatomical substrates of these phenomena remain largely uninvestigated [18,19,20,21]

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