Sex specific effects of “junk-food” diet on calcium permeable AMPA receptors and silent synapses in the nucleus accumbens core

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.

Insulin Bidirectionally Alters NAc Glutamatergic Transmission: Interactions between Insulin Receptor Activation, Endogenous Opioids, and Glutamate Release

“…3 excitatory transmission that underlies food-and drug-seeking behaviors (Oginsky et al, 2016;Wolf, 2016;Dong et al, 2017;Derman and Ferrario, 2018;Alonso-Caraballo et al, 2020;Ferrario, 2020). Thus, identifying neural mechanisms that regulate NAc excitatory transmission is fundamental to understanding the neurobiology of normal and aberrant motivation.…”

Metaplasticity in the Ventral Pallidum as a Potential Marker for the Propensity to Gain Weight in Chronic High-Calorie Diet

“…At the end of the dietinduced obesity protocol, HFHS mice were divided according to their weight gain (relative to their weight on day 1, when they were first exposed to the HFHS diet) into diet-induced WGs (top third of weight gainers) and NWGs (bottom third of weight gainers). These groups are parallel to, and were generated using the same protocols as, the obesityprone and obesity-resistant groups that we and others used in previous studies (Cifani et al, 2015;Brown et al, 2017;Inbar et al, 2019;Oginsky and Ferrario, 2019;Alonso-Caraballo et al, 2020).…”

Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders

“…Ca 2+ influx through CP-AMPARs is thought to play a critical role in synaptogenesis and formation of neuronal circuitry during early development (McDonald and Johnston, 1990;Stubblefield and Benke, 2010). In the adult brain, the CP-AMPARs are not typically present in most cells of the CNS and PNS, but their temporary increase may contribute to activity-dependent synaptic plasticity and the related behavioral phenotypes (Di et al, 2019;Manz et al, 2020;Alonso-Caraballo et al, 2021;Yu et al, 2021).…”