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Context-dependent fear memory retrieval involves two distinct populations of hippocampal neurons.

October 21, 2016

How context influences memories and behavior


Scientists in the group of Andreas Lüthi have identified two neuronal circuits that mediate the association of contextual information with emotional memories. In their publication in Cell, they describe networks of neurons that are active in the hippocampus and the amygdala, when we associate for example an unpleasant situation with a certain place. They also show that other, parallel neuronal networks are responsible for different integrations of context and emotional memories.

We all have experienced this: A hint of a perfume immediately catapults our mind back to the apartment where we used that perfume ten years ago. The dark unlit street instantly brings up the discomfort that we experienced on a similar street two weeks ago. Our memories about smells, sounds, sights, in fact, about all our sensory experiences, are tightly linked to impressions and emotions from the situation in which we experienced them. This not only brings back cherished memories, it also allows us to learn from past experiences and to react appropriately. However, how our brain links these emotional memories about sensory experiences to the context of the situation is poorly understood.

Scientists from the team of Andreas Lüthi, a group leader at the Friedrich Miescher Institute for Biomedical Research and Professor at the University of Basel, have now addressed this question. They have analyzed the neuronal networks that connect the hippocampus and the amygdala during fear memory formation. The hippocampus is of interest because it processes contextual information; the amygdala is an almond shaped region deep in the brain that encodes emotional reactions, such as fear, and is involved in memory formation.

Using trans-synaptic viruses that allow the identification of connected neurons, the scientists showed that there are multiple parallel connections between the ventral hippocampus and the amygdala. Through functional studies, the neuroscientists could then demonstrate that these different connections mediate distinct forms of conceptualization. For instance, one pathway connects the context to emotion: It is active when a mouse shows a fear reaction in a particular setting that it learned to fear, without the fearful stimulus. On the other hand, a second distinct pathway connecting a different set of neurons in the hippocampus and the amygdala is necessary for the retrieval of cued fear memories. In that setup, the mouse lost the fear memory in a particular situation but when exposed to the same unpleasant cue in a different setting, the fearful reaction returned.

"Our results show that context is processed in distinct but very specific ways,” explains Lüthi. “One network for example allows the formation of strong contextual fear memories, the other one preserves flexibility, where the mouse can adapt its behavior based on the context."

This study also shows that the analysis of the sophisticated and precise neuronal networks at a cellular resolution and not the coarse interplay of whole brain regions enables new insights into the versatility of brain processes.

Original publication
Xu C, Krabbe S, Gründemann J, Botta P, Fadok JP, Osakada F, Saur D, Grewe BF, Schnitzer MJ, Callaway EM, Lüthi A (2016) Distinct hippocampal output pathways mediate dissociable roles of context in associative memory retrieval. Cell, advance online publication

More about Andreas Lüthi
Andreas Lüthi is an expert in the field of learning processes in the brain. In particular, his work has provided us with a substantially better understanding of the type of brain activity that occurs when we learn to be afraid of something
» More about Andreas Lüthi

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