Creating a False Memory in the Hippocampus

By S. Ramirez, Xu Liu, Pei-Ann Lin, J. Suh, Michele Pignatelli, R. Redondo, T. Ryan, S. Tonegawa. 2013

908 citations recorded by the source corpus.

Can You Trust Your Memory? Being highly imaginative animals, humans constantly recall past experiences. These internally generated stimuli sometimes get associated with concurrent external stimuli, which can lead to the formation of false memories. Ramirez et al. (p. 387; see the cover) identified a population of cells in the dentate gyrus of the mouse hippocampus that encoded a particular context and were able to generate a false memory and study its neural and behavioral interactions with true memories. Optogenetic reactivation of memory engram–bearing cells was not only sufficient for the behavioral recall of that memory, but could also serve as a conditioned stimulus for the formation of an associative memory. Associations can be artificially created through reactivation of memory engrams in mouse dentate gyrus granule cells. Memories can be unreliable. We created a false memory in mice by optogenetically manipulating memory engram–bearing cells in the hippocampus. Dentate gyrus (DG) or CA1 neurons activated by exposure to a particular context were labeled with channelrhodopsin-2. These neurons were later optically reactivated during fear conditioning in a different context. The DG experimental group showed increased freezing in the original context, in which a foot shock was never delivered. The recall of this false memory was context-specific, activated similar downstream regions engaged during natural fear memory recall, and was also capable of driving an active fear response. Our data demonstrate that it is possible to generate an internally represented and behaviorally expressed fear memory via artificial means.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Neuroscience, Cognitive Science & Psychology

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Citations in the corpus

Continual Learning with Deep Generative Replay (2017, background): “Altering the reactivation causes a defect in consolidated memory [35], while co-stimulating certain memory traces in the hippocampus creates a false memory that was never experienced [28].”
NISPA: Neuro-Inspired Stability-Plasticity Adaptation for Continual Learning in Sparse Networks (2022, background): “From a neuroscience perspective storing raw data is not biologically plausible (Hadsell et al., 2020; van de Ven et al., 2020; Hayes et al., 2021; Ramirez et al., 2013).”
Memory Engram Cells Have Come of Age. (2015, neutral): “, 2012), a recent study tested this possibility in mice (Ramirez et al., 2013).”
Hippocampal Binding of Novel Information with Dominant Memory Traces Can Support Both Memory Stability and Change (2014, background): “This idea was supported recently by a study that directly stimulated neurons in the hippocampus to induce reactivation of a familiar context memory during contextual fear conditioning in a novel context (Ramirez et al., 2013).”
The content of hippocampal “replay” (2018, background): “Among several lines of investigation attempting to address this question (Garner et al., 2012; Josselyn et al., 2015; Ramirez et al., 2013; Tse et al., 2007), hippocampal ripples and ripple-based “replay” have emerged as strong candidate mechanisms which may facilitate both the initial storage and…”
Memory engrams: Recalling the past and imagining the future (2020, background): “Chemogenetically reactivating these neurons while mice were fear conditioned in context B produced a “hybrid or synthetic” context representation that was not retrievable by either context alone [unlike (46), above].”
Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory. (2015, positive): “For this purpose, we injected AAV2/9-TRE-mCherry into CA3 of c-fos tTA mice (Reijmers et al., 2007) and exposed them to Context A while off Dox so as to label activated CA3 cells with mCherry (Ramirez et al., 2013).”
Awake reactivation of emotional memory traces through hippocampal-neocortical interactions (2016, positive): “On the other hand, the amygdala may be involved as a consequence, because activation of dentate gyrus cell assemblies related to a fear memory seem to be sufficient to cause amygdala activation (Ramirez et al., 2013).”