Philosophical Transactions of the Royal Society B: Biological Sciences
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Comparing behaviours induced by natural memory retrieval and optogenetic reactivation of an engram ensemble in mice

Sungmo Park

Sungmo Park

Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada

Contribution: Data curation, Formal analysis, Investigation, Methodology, Writing – review and editing

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Sang Yoon Ko

Sang Yoon Ko

Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada

Department of Physiology, University of Toronto, Toronto, Ontario M5G 1X8, Canada

Contribution: Data curation, Formal analysis, Investigation, Writing – review and editing

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Paul W. Frankland

Paul W. Frankland

Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada

Department of Physiology, University of Toronto, Toronto, Ontario M5G 1X8, Canada

Department of Psychology, University of Toronto, Toronto, Ontario M5G 1X8, Canada

Contribution: Conceptualization, Funding acquisition, Methodology, Supervision, Writing – review and editing

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Sheena A. Josselyn

Sheena A. Josselyn

Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada

Department of Physiology, University of Toronto, Toronto, Ontario M5G 1X8, Canada

Department of Psychology, University of Toronto, Toronto, Ontario M5G 1X8, Canada

[email protected]

Contribution: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft

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    Memories are thought to be stored within sparse collections of neurons known as engram ensembles. Neurons active during a training episode are allocated to an engram ensemble (‘engram neurons’). Memory retrieval is initiated by external sensory or internal cues present at the time of training reactivating engram neurons. Interestingly, optogenetic reactivation of engram ensemble neurons alone in the absence of external sensory cues is sufficient to induce behaviour consistent with memory retrieval in mice. However, there may exist differences between the behaviours induced by natural retrieval cues or artificial engram reactivation. Here, we compared two defensive behaviours (freezing and the syllable structure of ultrasonic vocalizations, USVs) induced by sensory cues present at training (natural memory retrieval) and optogenetic engram ensemble reactivation (artificial memory retrieval) in a threat conditioning paradigm in the same mice. During natural memory recall, we observed a strong positive correlation between freezing levels and distinct USV syllable features (characterized by an unsupervised algorithm, MUPET (Mouse Ultrasonic Profile ExTraction)). Moreover, we observed strikingly similar behavioural profiles in terms of freezing and USV characteristics between natural memory recall and artificial memory recall in the absence of sensory retrieval cues. Although our analysis focused on two behavioural measures of threat memory (freezing and USV characteristics), these results underscore the similarities between threat memory recall triggered naturally and through optogenetic reactivation of engram ensembles.

    This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.

    Footnotes

    One contribution of 26 to a discussion meeting issue ‘Long-term potentiation: 50 years on’.

    References