Differential activation of amygdala Arc expression by positive and negatively valenced emotional learning conditions.

Erica J Young,Cedric L Williams

doi:10.3389/fnbeh.2013.00191

Abstract

Norepinephrine is released in the amygdala following negatively arousing learning conditions. This event initiates a cascade of changes including the transcription of activity-regulated cytoskeleton-associated protein (Arc) expression, an early-immediate gene associated with memory encoding. Recent evidence suggests that the valence of emotionally laden encounters may generate lateralized, as opposed to symmetric release of this transmitter in the right or left amygdala. It is currently not clear if valence-induced patterns of selective norepinephrine output across hemispheres are also reproduced in downstream pathways of cellular signaling necessary for memory formation. This question was addressed by determining if Arc expression is differentially distributed across the right and left amygdala following exposure to positively or negatively valenced learning conditions respectively. Male Sprague Dawley rats were randomly assigned to groups exposed to the Homecage only, five auditory tones only, or five auditory tones paired with footshock (0.35 mA) during Pavlovian fear conditioning. Western blot analysis revealed that Arc expression in the right amygdala was elevated significantly above that observed in the left amygdala 60 and 90 min following fear conditioning. Similarly, subjects exposed to a negatively valenced outcome consisting of an unexpected reduction in food rewards showed a greater level of Arc expression in only the right, but not left basolateral amygdala. Presenting a positively valenced event involving an unexpected increase in food reward magnitude following bar pressing, resulted in significantly greater Arc expression in the left, but not right basolateral amygdala (p < 0.01). These findings indicate that the valence of emotionally arousing learning conditions is reflected at later stages of synaptic plasticity involving the transcription of immediate early genes such as Arc.

Highlights

Converging evidence suggests that the left and right amygdala are preferentially activated during the encoding of emotional events containing positive or negatively valenced stimuli
Protein levels of animals subjected to negatively valenced stimuli during Pavlovian conditioning was compared to controls that experienced tone presentations in the absence of footshock or controls that remained within their homecage
Previous reports from functional scans (Morris et al, 1999; Zalla et al, 2000; Hamann et al, 2002; Etkin et al, 2004), lesions (Blundell and Adamec, 2007; Orman and Stewart, 2007; Carrasquillo and Gereau, 2008), and electrophysiology studies (Lanteaume et al, 2007; Ji and Neugebauer, 2009) indicate that the amygdala encodes emotionally arousing events differentially, depending on the valence of the stimuli a novel finding to emerge from our lab is that norepinephrine released in the basolateral amygdala encodes negatively or positively arousing learning tasks through asymmetric norepinephrine release in right or left basolateral amygdala, respectively (Young and Williams, 2010)

Summary

Introduction

Converging evidence suggests that the left and right amygdala are preferentially activated during the encoding of emotional events containing positive or negatively valenced stimuli. Elevated levels of protein kinase C (PKC) or cyclic AMP response element binding protein (CREB) are integral components of the molecular cascades that convert new information from short, to long term memory (Zhou et al, 2009; de Oliveira Coelho et al, 2013; Pinho et al, 2013) Both proteins are upregulated in the right, but not left amygdala after exposure to a tone previously paired with an aversive experience such as footshock during fear conditioning training or in response to exposure to a threatening predator (Blundell and Adamec, 2007; Orman and Stewart, 2007). Inflammation-induced mechanical sensitivity is reduced by blocking right amygdala

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