Noradrenergic activation of the basolateral amygdala enhances object recognition memory and induces chromatin remodeling in the insular cortex.

Hassiba Beldjoud,Areg Barsegyan,Benno Roozendaal

doi:10.3389/fnbeh.2015.00108

Hassiba Beldjoud, Areg Barsegyan + Show 1 more

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https://doi.org/10.3389/fnbeh.2015.00108

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Abstract

It is well established that arousal-induced memory enhancement requires noradrenergic activation of the basolateral complex of the amygdala (BLA) and modulatory influences on information storage processes in its many target regions. While this concept is well accepted, the molecular basis of such BLA effects on neural plasticity changes within other brain regions remains to be elucidated. The present study investigated whether noradrenergic activation of the BLA after object recognition training induces chromatin remodeling through histone post-translational modifications in the insular cortex (IC), a brain region that is importantly involved in object recognition memory. Male Sprague—Dawley rats were trained on an object recognition task, followed immediately by bilateral microinfusions of norepinephrine (1.0 μg) or saline administered into the BLA. Saline-treated control rats exhibited poor 24-h retention, whereas norepinephrine treatment induced robust 24-h object recognition memory. Most importantly, this memory-enhancing dose of norepinephrine induced a global reduction in the acetylation levels of histone H3 at lysine 14, H2B and H4 in the IC 1 h later, whereas it had no effect on the phosphorylation of histone H3 at serine 10 or tri-methylation of histone H3 at lysine 27. Norepinephrine administered into the BLA of non-trained control rats did not induce any changes in the histone marks investigated in this study. These findings indicate that noradrenergic activation of the BLA induces training-specific effects on chromatin remodeling mechanisms, and presumably gene transcription, in its target regions, which may contribute to the understanding of the molecular mechanisms of stress and emotional arousal effects on memory consolidation.

Highlights

Enhanced memory for emotionally arousing events is a well-recognized phenomenon, which has obvious adaptive value in evolutionary terms, as it is vital to remember both dangerous and favorable situations (Roozendaal and McGaugh, 2011)
We examined different histone post-translational modifications (PTMs) marks that have been reported to be involved in learning and memory and/or stress adaptation such as acetylation of histone H3 at lysine 14, acetylation of histone H2B, acetylation of histone H4, phosphorylation of histone H3 at serine 10 and tri-methylation of histone H3 at lysine 27 (3meH3K27) (Chwang et al, 2006; Fischer et al, 2007; Hunter et al, 2009; Koshibu et al, 2009, 2011; Bousiges et al, 2010; Gräff et al, 2012)
A Memory-Enhancing Dose of Norepinephrine Administered into the basolateral complex of the amygdala (BLA) After Object Recognition Training Reduces Histone Acetylation Levels in the insular cortex (IC). To determine whether this memory-enhancing dose of norepinephrine administered into the BLA after object recognition training triggers changes in the chromatin state in the IC, we examined changes in the following histone markers: acetylation of histone H3 at lysine 14, acetylation of histone H2B and acetylation of histone H4, as well as phosphorylation of histone H3 at serine 10 and tri-methylation of histone H3 at lysine 27 (3meH3K27)

Summary

Introduction

Enhanced memory for emotionally arousing events is a well-recognized phenomenon, which has obvious adaptive value in evolutionary terms, as it is vital to remember both dangerous and favorable situations (Roozendaal and McGaugh, 2011). Basolateral amygdala, memory, and chromatin modifications indicates that noradrenergic activation of the basolateral complex of the amygdala (BLA) is critically involved in mediating emotional arousal effects on memory enhancement by influencing synaptic plasticity and information storage processes in other brain regions (Introini-Collison et al, 1991; Ferry et al, 1999; Hatfield and McGaugh, 1999; Roozendaal et al, 2002, 2009; LaLumiere et al, 2003; Huff et al, 2005; Barsegyan et al, 2014). Noradrenergic activation of the BLA enhances the consolidation of low-arousing object recognition memory (Roozendaal et al, 2008), a naturalistic task based on the spontaneous tendency of rodents to explore a novel object more than a familiar one (Ennaceur and Delacour, 1988). The finding that noradrenergic blockade of the BLA prevents the effect of drug administration into the IC on conditioned taste aversion as well as inhibitory avoidance memory (Miranda and McGaugh, 2004), provides important support for the view that noradrenergic activity of the BLA regulates neural plasticity and memory consolidation processes within this brain region

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