Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training.

Raquel V Fornari,Erika Atucha,Ellie Eggens-Meijer,Benno Roozendaal,Tifany Desprez,Romy Wichmann

doi:10.3389/fnbeh.2012.00010

Abstract

Glucocorticoids are known to enhance the consolidation of memory of emotionally arousing experiences by acting upon a network of interconnected brain regions. Although animal studies typically do not consider the insular cortex (IC) to be part of this network, the present findings indicate that the IC is importantly involved in regulating glucocorticoid effects on memory consolidation of emotionally arousing inhibitory avoidance training. The specific glucocorticoid receptor (GR) agonist RU 28362 (3 or 10 ng in 0.5 μl) infused bilaterally into the IC of male Sprague–Dawley rats immediately after one-trial inhibitory avoidance training dose-dependently enhanced 48 h retention performance. Moreover, training on the inhibitory avoidance task increased neuronal activity of the IC, as assessed by an increased number of cells expressing immunoreactivity for phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). However, systemic administration of a memory-enhancing dose of corticosterone (1 mg/kg) after inhibitory avoidance training rapidly reduced the number of pERK1/2-positive cells in the IC, suggesting that glucocorticoid administration reduces overall neuronal activity of the IC. To investigate which components of the inhibitory avoidance training experience were influenced by the intra-IC glucocorticoid administration, in the last experiment rats were trained on a modified inhibitory avoidance task in which context exposure and footshock training occur on two sequential days. RU 28362 administration into the IC enhanced later retention when infused immediately after either the context or footshock training. Thus, these findings indicate that the IC mediates glucocorticoid effects on the consolidation of memory of different components of inhibitory avoidance training and suggest that the IC might be an important element of the rodent brain network involved in emotional regulation of learning and memory.

Highlights

Glucocorticoid hormones—stress hormones released from the adrenal cortex—are known to strengthen the consolidation of memory of emotionally arousing experiences (de Kloet et al, 1999; Roozendaal, 2000; Joëls et al, 2006; Sandi and PineloNava, 2007; de Quervain et al, 2009; Roozendaal and McGaugh, 2011; Schwabe et al, 2012)
We investigated whether the specific glucocorticoid receptor (GR) agonist RU 28362 administered into the insular cortex (IC) immediately after one-trial inhibitory avoidance training enhances long-term retention of the training experience
GR AGONIST ADMINISTRATION INTO THE INSULAR CORTEX ENHANCES MEMORY CONSOLIDATION OF INHIBITORY AVOIDANCE TRAINING This experiment examined whether the GR agonist RU 28362 infused into the IC enhances the consolidation of memory of inhibitory avoidance training

Summary

Introduction

Glucocorticoid hormones—stress hormones released from the adrenal cortex—are known to strengthen the consolidation of memory of emotionally arousing experiences (de Kloet et al, 1999; Roozendaal, 2000; Joëls et al, 2006; Sandi and PineloNava, 2007; de Quervain et al, 2009; Roozendaal and McGaugh, 2011; Schwabe et al, 2012). Most animal studies investigating glucocorticoid-induced enhancement of memory consolidation examined their effects on a network of interacting brain regions involved in emotional regulation of memory, including the basolateral amygdala (BLA), prefrontal cortex and hippocampus (Micheau et al, 1984; Roozendaal and McGaugh, 1997a,b, 2011; Roozendaal et al, 2008, 2009b; Miranda et al, 2008b). Human neuroimaging studies generally support an involvement of these brain regions, as well as their functional interaction, in emotionally influenced learning and memory (Buchel et al, 1998; Richardson et al, 2004; Marschner et al, 2008; Shin and Liberzon, 2010), they consistently point to a key role for the insular cortex (IC) (Craig, 2009; Menon and Uddin, 2010; Shin and Liberzon, 2010; Hartley et al, 2011; Ille et al, 2011). Increased anterior insula activity has been reported during the subjective awareness of both positive and negative emotions (Craig, 2009; Menon and Uddin, 2010) as well as during the encoding and recall of a broad spectrum of emotionally salient learning tasks (Buchel et al, 1998; Alvarez et al, 2008, 2011; Marschner et al, 2008; King et al, 2009; Rasch et al, 2009).

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