Sex specific effects of \u201cjunk-food\u201d diet on calcium permeable AMPA receptors and silent synapses in the nucleus accumbens core

Yanaira Alonso-Caraballo,Travis E Brown,Carrie R Ferrario,Tracy L Fetterly,Allison M Nieto,Emily T Jorgensen

doi:10.1038/s41386-020-0781-1

Yanaira Alonso-Caraballo, Travis E Brown + Show 4 more

Open Access

https://doi.org/10.1038/s41386-020-0781-1

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Abstract

CP-AMPARs in the nucleus accumbens (NAc) mediate cue-triggered motivation for food and cocaine. In addition, increases in NAc CP-AMPAR expression and function can be induced by cocaine or sugary, fatty junk-foods. However, the precise nature of these alterations and the degree to which they rely on the same underlying mechanisms is not well understood. This has important implications for understanding adaptive vs. maladaptive plasticity that drives food- and drug-seeking behaviors. Furthermore, effects of junk-foods on glutamatergic plasticity in females are unknown. Here, we use a combination of protein biochemistry and whole-cell patch clamping to determine effects of diet manipulation on glutamatergic plasticity within the NAc of males and females. We found that junk-food consumption increases silent synapses and subsequently increases CP-AMPAR levels in males in the NAc of male rats. In addition, a brief period of junk-food deprivation is needed for the synaptic insertion of CP-AMPARs and the maturation of silent synapses in males. In contrast, junk-food did not induce AMPAR plasticity in females but may instead alter NMDAR-mediated transmission. Thus, these studies reveal sex differences in the effects of junk-food on NAc synaptic plasticity. In addition, they provide novel insights into how essential food rewards alter NAc function.

Highlights

Activity in mesocorticolimbic circuits influences a range of motivational processes including the pursuit of food and drug rewards
We found that junk-food consumption increases silent synapses and subsequently increases CP-AMPAR levels in males in the nucleus accumbens (NAc) of male rats
These results are discussed in light of the established time course of NAc CP-AMPAR and silent synapse plasticity produced by cocaine

Summary

Introduction

Activity in mesocorticolimbic circuits influences a range of motivational processes including the pursuit of food and drug rewards. Understanding the potential effects of sugary, fatty junk-foods (JFs) on mesocorticolimbic systems and motivational processes has become increasingly important as the obesity epidemic continues to rise worldwide. Glutamatergic plasticity within the NAc core is a key mediator of enhanced motivation for both food and cocaine [7,8,9,10]. Cue-triggered food seeking and the “incubation” of cocaine seeking after prolonged withdrawal are mediated by activation of high conductance calcium permeable-AMPA receptors (CP-AMPARs) within the NAc core [11, 12]. Consumption of a sugary, fatty JF diet enhances NAc CP-AMPARmediated transmission and expression [13] and potentiates cuetriggered food seeking in males [14]. Whether the processes mediating CP-AMPAR upregulation are ubiquitous or specific to JF vs. cocaine experience is unknown

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