Aversive memory engrams in the hippocampus

Negative episodic memories exert important control of behavioral responses during a real or anticipated threatening situation. Under pathological states, however, this control can extend to non-threatening scenarios. For example, pathological states of aversive memory involve fear-overgeneralization in post-traumatic stress disorder (PTSD) or other anxiety disorders. Furthermore, negative bias in cognitive processing and memory formation is seen in depressed individuals displaying enhanced encoding and recall, less forgetting or repetition of negative memory (rumination) as well as impaired recall of positive memory. Beyond pathological conditions, researchers have long aimed to understand the basic biological entity of memory. This unit termed “engram” is the cellular and molecular component of enduring physiological changes in the brain, enabling learning and memory retrieval. Herein, the hippocampus is central in the formation of context-dependent episodic memories and therefore most often studied in animal experiments to elucidate complex memory traces. In addition, the hippocampus is critically involved in fear-circuits and stress-related dysfunction. This review summarizes current knowledge about memory engrams in hippocampal (sub)regions and their functional relevance regarding neuronal correlates and rodent behavior. A special focus is placed on the negative valence of a memory and the formation of engrams for aversive memories, specifically induced by fear or stress. Finally, limitations of current engram research and possible future directions to improve our understanding of negatively valued memory and its implications in neuropathological conditions will be discussed.