Bidirectional switch of the valence associated with a hippocampal contextual memory engram

By R. Redondo, Joshua Kim, Autumn L Arons, S. Ramirez, Xu Liu, S. Tonegawa. 2014

454 citations recorded by the source corpus.

The valence of memories is malleable because of their intrinsic reconstructive property. This property of memory has been used clinically to treat maladaptive behaviours. However, the neuronal mechanisms and brain circuits that enable the switching of the valence of memories remain largely unknown. Here we investigated these mechanisms by applying the recently developed memory engram cell- manipulation technique. We labelled with channelrhodopsin-2 (ChR2) a population of cells in either the dorsal dentate gyrus (DG) of the hippocampus or the basolateral complex of the amygdala (BLA) that were specifically activated during contextual fear or reward conditioning. Both groups of fear-conditioned mice displayed aversive light-dependent responses in an optogenetic place avoidance test, whereas both DG- and BLA-labelled mice that underwent reward conditioning exhibited an appetitive response in an optogenetic place preference test. Next, in an attempt to reverse the valence of memory within a subject, mice whose DG or BLA engram had initially been labelled by contextual fear or reward conditioning were subjected to a second conditioning of the opposite valence while their original DG or BLA engram was reactivated by blue light. Subsequent optogenetic place avoidance and preference tests revealed that although the DG-engram group displayed a response indicating a switch of the memory valence, the BLA-engram group did not. This switch was also evident at the cellular level by a change in functional connectivity between DG engram-bearing cells and BLA engram-bearing cells. Thus, we found that in the DG, the neurons carrying the memory engram of a given neutral context have plasticity such that the valence of a conditioned response evoked by their reactivation can be reversed by re-associating this contextual memory engram with a new unconditioned stimulus of an opposite valence. Our present work provides new insight into the functional neural circuits underlying the malleability of emotional memory.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

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Citations in the corpus

Memory Engram Cells Have Come of Age. (2015, unknown): “For contextual fear or reward memory, distinct subpopulations of BLA cells are also recruited to provide engrams for negative or positive valence (Redondo et al., 2014; Gore et al., 2015).”
Memory engrams: Recalling the past and imagining the future (2020, background): “For instance, in contextual fear memory, hippocampal (DG, CA3, and CA1) engram cell ensembles may represent the context (40, 48, 91–93), whereas amygdala engram cell ensembles may represent valence information (69, 71, 75), and cortical engram cell ensembles may represent distinct sensory informatio”
Optogenetic and pharmacological suppression of spatial clusters of face neurons reveal their causal role in face gender discrimination (2015, background): “4C), which implies that emerging technology that allows labeling and optogenetic targeting of differently tuned neural populations within cortical subregions (34, 35) should, in principle, allow us to extend our approach to that finer spatial scale.”
Neural Circuit Motifs in Valence Processing (2018, unknown): “Causal manipulations of valence-encoding cell populations targeting immediate early genes (Gore et al., 2015; Redondo et al., 2014) or transcription factors (Han et al.”