Dynamic behavior of the locus coeruleus during arousal-related memory processing in a multi-modal 7T fMRI paradigm.

Heidi IL Jacobs,Kâmil Uludağ,Linda HG Pagen,Frans RJ Verhey,Dimo Ivanov,Nikos Priovoulos,Benedikt A Poser

doi:10.7554/elife.52059

Abstract

A body of animal and human evidence points to the norepinephrine (NE) locus coeruleus (LC) system in modulating memory for arousing experiences, but whether the LC would recast its role along memory stages remains unknown. Sedation precluded examination of LC dynamics during memory processing in animals. Here, we addressed the contribution of the LC during arousal-associated memory processing through a unique combination of dedicated ultra-high-field LC-imaging methods, a well-established emotional memory task, online physiological and saliva alpha-amylase measurements in young adults. Arousal-related LC activation followed amygdala engagement during encoding. During consolidation and recollection, activation transitioned to hippocampal involvement, reflecting learning and model updating. NE-LC activation is dynamic, plays an arousal-controlling role, and is not sufficient but requires interactions with the amygdala to form adaptive memories of emotional experiences. These findings have implications for understanding contributions of LC dysregulation to disruptions in emotional memory formation, observed in psychiatric and neurocognitive disorders.

Highlights

Multiple decades of neuroscience and psychology research uncovered that arousal contributes to enhanced memory performance and that norepinephrine (NE) transmission plays a pivotal role in this phenomenon (van Stegeren, 2008; Roozendaal and McGaugh, 2011)
A second resting-state scan was collected. This was followed with a recollection fMRIscan, during which participants had to indicate whether they recognized the face and, upon endorsement, had to select the name of the face out of three options
The extracted beta-coefficients of this contrast correlated with emotional memory performance (r = 0.506, N = 24, p=0.019), indicating that higher locus coeruleus (LC) activity in emotionally encoded trials under high arousal as compared to neutral trials was related to better memory performance. These results suggest that the MTL and basolateral amygdala (BLA) is involved in the accuracy of learning, while LC clusters are involved in encoding of emotional stimuli, a role that is modulated by arousal

Summary

Introduction

Multiple decades of neuroscience and psychology research uncovered that arousal contributes to enhanced memory performance and that norepinephrine (NE) transmission plays a pivotal role in this phenomenon (van Stegeren, 2008; Roozendaal and McGaugh, 2011). The NE-LC system has widespread efferents to almost the entire brain and can modulate cognition, behavior and autonomic tone via its effects on adrenoreceptors in target neurons (Sara, 2009; Sara and Bouret, 2012; Samuels and Szabadi, 2008a). Research into NE-modulation of emotional memory enhancement has focused largely on the amygdala (Hermans et al, 2014; Phelps and LeDoux, 2005; McIntyre et al, 2003), an important target region of the LC and a critical nexus in memory for arousing experiences. Rodent work consistently demonstrated that blocking b-adrenergic receptors in the basolateral amygdala (BLA) immediately after learning in arousing conditions impairs memory, while infusion of NE or b-adrenoreceptor agonists enhances consolidation and rescinds the impairment, evaluated one to two days later

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