Creating a False Memory in the Hippocampus (original) (raw)

Optogenetics and the Mechanism of False Memory

Constructivists about memory argue that memory is a capacity for building representations of past events from a generalized information store (e.g., De Brigard, in Synthese 191:155–185, 2014a; Michaelian, in Philos Psychol 24:323–342, 2012). The view is motivated by the memory errors discovered in cognitive psychology. Little has been known about the neural mechanisms by which false memories are produced. Recently, using a method I call the Optogenetic False Memory Technique (O-FaMe), neuroscientists have created false memories in mice (e.g., Ramirez et al., in Science 341:388–391, 2013). In this paper, I examine how Constructivism fares in light of O-FaMe results. My aims are two-fold. First, I argue that errors found in O-FaMe and cognitive psychology are similar behaviorally. Second, Constructivists should be able to explain the former since they purport to explain the latter, but they cannot. I conclude that O-FaMe studies reveal details about the mechanism by which false memories are produced that are incompatible with the explanatory approach to false memories favored by Constructivism.

Hippocampal activity predicts contextual misattribution of false memories

The Proceedings of the National Academy of Sciences, 2023

Failure of contextual retrieval can lead to false recall, wherein people retrieve an item or experience that occurred in a different context or did not occur at all. Whereas the hippocampus is thought to play a crucial role in memory retrieval, we lack understanding of how the hippocampus supports retrieval of items related to a target context while disregarding related but irrelevant information. Using direct electrical recordings from the human hippocampus, we investigate the neural process underlying contextual misattribution of false memories. In two large datasets, we characterize key physiological differences between correct and false recalls that emerge immediately prior to vocalization. By differentiating between false recalls that share high or low contextual similarity with the target context, we show that low-frequency activity (6 to 18 Hz) in the hippocampus tracks similarity between the current and retrieved context. Applying multivariate decoding methods, we were able to reliably predict the contextual source of the to-be-recalled item. Our findings elucidate one of the hallmark features of episodic memory: our ability to distinguish between memories that were formed on different occasions.

Hippocampal mechanisms of false recall

Research Square (Research Square), 2022

Failure of contextual retrieval can lead to false recall, wherein people retrieve an item or experience that occurred in a different context, or did not occur at all. Whereas the hippocampus is thought to play a crucial role in contextually-mediated retrieval, the neural process leading to false recalls is not yet understood. Using direct electrical recordings from the human hippocampus, we investigate the neural mechanisms underlying the false recall phenomenon. In two large datasets, we characterize key physiological differences between correct and false recalls, emerging immediately prior to vocalization. By differentiating between false recalls that share high or low contextual similarity with the target context, we identify the neural process underlying retrieval of item-context associations. Applying multivariate decoding methods, we were able to reliably predict whether the to-be-recalled item would be a veridical or false memory. Our findings provide a mechanistic insight into the process of retrieving context-bound memories, and open new avenues for interventions aimed at reducing false recalls when those lead to functional impairment.

Artificially Enhancing and Suppressing Hippocampus-Mediated Memories

Current Biology, 2019

Highlights d Acute activation of dorsal and ventral HPC engrams in mice drives reward and aversion d The ventral DG is preferentially reactivated in emotionally salient contexts d Chronic activation of HPC engrams decreases or increases context-specific freezing d Memory enhancement is disrupted when BLA cells processing fear are silenced

Identification and optogenetic manipulation of memory engrams in the hippocampus

With the accumulation of our knowledge about how memories are formed, consolidated, retrieved, and updated, neuroscience is now reaching a point where discrete memories can be identified and manipulated at rapid timescales. Here, we start with historical studies that lead to the modern memory engram theory. Then, we will review recent advances in memory engram research that combine transgenic and optogenetic approaches to reveal the underlying neuronal substrates sufficient for activating mnemonic processes. We will focus on three concepts: (1) isolating memory engrams at the level of single cells to tag them for subsequent manipulation; (2) testing the sufficiency of these engrams for memory recall by artificially activating them; and (3) presenting new stimuli during the artificial activation of these engrams to induce an association between the two to form a false memory. We propose that hippocampal cells that show activitydependent changes during learning construct a cellular basis for contextual memory engrams.

Optogenetic stimulation of a hippocampal engram activates fear memory recall

A specific memory is thought to be encoded by a sparse population of neurons 1,2 . These neurons can be tagged during learning for subsequent identification 3 and manipulation 4-6 . Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) 7,8 and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fearconditioned in a different context, suggesting that light-induced fear memory recall is context-specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.

Enhance, delete, incept: Manipulating hippocampus-dependent memories

Brain Research Bulletin, 2014

Here we provide a brief overview of recent research on memory manipulation. We focus primarily on memories for which the hippocampus is thought to be required due to its central importance in the study of memory. The repertoire of methods employed is expanding and includes optogenetics, transcranial stimulation, deep brain stimulation, cued reactivation during sleep and the use of pharmacological agents. In addition, the possible mechanisms underlying these memory changes have been investigated using techniques such as single unit recording and functional magnetic resonance imaging (fMRI). This article is part of a Special Issue entitled 'Memory enhancement'.

Hippocampal Memory Traces Are Differentially Modulated by Experience, Time, and Adult Neurogenesis

Memory traces are believed to be ensembles of cells used to store memories. To visualize memory traces, we created a transgenic line that allows for the comparison between cells activated during encoding and expression of a memory. Mice re-exposed to a fearinducing context froze more and had a greater percentage of reactivated cells in the dentate gyrus (DG) and CA3 than mice exposed to a novel context. Over time, these differences disappeared, in keeping with the observation that memories become generalized. Optogenetically silencing DG or CA3 cells that were recruited during encoding of a fear-inducing context prevented expression of the corresponding memory. Mice with reduced neurogenesis displayed less contextual memory and less reactivation in CA3 but, surprisingly, normal reactivation in the DG. These studies suggest that distinct memory traces are located in the DG and in CA3 but that the strength of the memory is related to reactivation in CA3.

Hippocampal Neural Assemblies and Conscious Remembering

Journal of Neurophysiology, 2008

The hippocampal formation is needed to encode episodic memories, which may be consciously recalled at some future time. This review examines recent advances in understanding recollection in the context of spatiotemporally organized relational memory coding and discusses predictions and challenges for future research on conscious remembering.