Contextual memory engrams, and the neuromodulatory influence of the locus coeruleus

Abstract

Here, we review the basis of contextual memory at a conceptual and cellular level. We begin with an overview of the philosophical foundations of traversing space, followed by theories covering the material bases of contextual representations in the hippocampus (engrams), exploring functional characteristics of the cells and subfields within. Next, we explore various methodological approaches for investigating contextual memory engrams, emphasizing plasticity mechanisms. This leads us to discuss the role of neuromodulatory inputs in governing these dynamic changes. We then outline a recent hypothesis involving noradrenergic and dopaminergic projections from the locus coeruleus (LC) to different subregions of the hippocampus, in sculpting contextual representations, giving a brief description of the neuroanatomical and physiological properties of the LC. Finally, we examine how activity in the LC influences contextual memory processes through synaptic plasticity mechanisms to alter hippocampal engrams. Overall, we find that phasic activation of the LC plays an important role in promoting new learning and altering mnemonic processes at the behavioral and cellular level through the neuromodulatory influence of NE/DA in the hippocampus. These findings may provide insight into mechanisms of hippocampal remapping and memory updating, memory processes that are potentially dysregulated in certain psychiatric and neurodegenerative disorders.

Keywords: contextual memory; engram; hippocampus; locus coeruleus; memory-updating; neuromodulation; norepinephrine; remapping.