Pharmacogenetic reactivation of the original engram evokes an extinguished fear memory

Yoshii, Toshitaka; Hosokawa, Hiroshi; Matsuo, Naoki

doi:10.1016/j.neuropharm.2016.09.012

Cited by 17 publications

(10 citation statements)

References 37 publications

(53 reference statements)

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“…Therefore, after extinction training, the ability of the CS to induce memory expression is diminished, suggesting that the original engram may be silenced. Consistent with this notion, some fear extinction protocols induce synaptic depotentation (reversal of synaptic potentiation induced by fear conditioning) of LA neurons (135), and, shortly after extinction training chemogenetic activation of cells tagged brain-wide during context fear training may increase freezing levels (136).…”

Section: Silent Engrams and Extinctionmentioning

confidence: 76%

Memory engrams: Recalling the past and imagining the future

Josselyn

Tonegawa

2020

Science

740

603

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In 1904, Richard Semon introduced the term “engram” to describe the neural substrate for storing memories. An experience, Semon proposed, activates a subset of cells that undergo off-line, persistent chemical and/or physical changes to become an engram. Subsequent reactivation of this engram induces memory retrieval. Although Semon’s contributions were largely ignored in his lifetime, new technologies that allow researchers to image and manipulate the brain at the level of individual neurons has reinvigorated engram research. We review recent progress in studying engrams, including an evaluation of evidence for the existence of engrams, the importance of intrinsic excitability and synaptic plasticity in engrams, and the lifetime of an engram. Together, these findings are beginning to define an engram as the basic unit of memory.

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Section: Silent Engrams and Extinctionmentioning

confidence: 76%

Memory engrams: Recalling the past and imagining the future

Josselyn

Tonegawa

2020

Science

740

603

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“…We employed mice expressing a short-lived version of the enhanced green fluorescent protein (eGFP) under the control of the C-fos gene promoter [ 11 ], reportedly restricted to excitatory neurons [ 12 , 13 ]. The short half-life of the protein, as well as the fact that it is not a conjugate of c-Fos, makes it ideal for in vivo tracking of immediate-early gene expression across multiple imaging sessions.…”

Section: Resultsmentioning

confidence: 99%

Spatial Memory Engram in the Mouse Retrosplenial Cortex

2018

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SummaryMemory relies on lasting adaptations of neuronal properties elicited by stimulus-driven plastic changes [1]. The strengthening (and weakening) of synapses results in the establishment of functional ensembles. It is presumed that such ensembles (or engrams) are activated during memory acquisition and re-activated upon memory retrieval. The retrosplenial cortex (RSC) has emerged as a key brain area supporting memory [2], including episodic and topographical memory in humans [3, 4, 5], as well as spatial memory in rodents [6, 7]. Dysgranular RSC is densely connected with dorsal stream visual areas [8] and contains place-like and head-direction cells, making it a prime candidate for integrating navigational information [9]. While previous reports [6, 10] describe the recruitment of RSC ensembles during navigational tasks, such ensembles have never been tracked long enough to provide evidence of stable engrams and have not been related to the retention of long-term memory. Here, we used in vivo 2-photon imaging to analyze patterns of activity of over 6,000 neurons within dysgranular RSC. Eight mice were trained on a spatial memory task. Learning was accompanied by the gradual emergence of a context-specific pattern of neuronal activity over a 3-week period, which was re-instated upon retrieval more than 3 weeks later. The stability of this memory engram was predictive of the degree of forgetting; more stable engrams were associated with better performance. This provides direct evidence for the interdependence of spatial memory consolidation and RSC engram formation. Our results demonstrate the participation of RSC in spatial memory storage at the level of neuronal ensembles.

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“…The reactivation experiments of such cell assemblies are possible not only by optogenetics but also by other genetic modifications and pharmacological manipulations (Matsuo, 2015 ; Yoshii et al, 2016 ). Therefore, there is no doubt that further studies of the causal relationship between cell-assembly activity and behavior will further advance.…”

Section: Experimental Detection 2—optogeneticsmentioning

confidence: 99%

Multiple Approaches to the Investigation of Cell Assembly in Memory Research—Present and Future

Sakurai

Osako

Tanisumi

et al. 2018

Front. Syst. Neurosci.

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In this review article we focus on research methodologies for detecting the actual activity of cell assemblies, which are populations of functionally connected neurons that encode information in the brain. We introduce and discuss traditional and novel experimental methods and those currently in development and briefly discuss their advantages and disadvantages for the detection of cell-assembly activity. First, we introduce the electrophysiological method, i.e., multineuronal recording, and review former and recent examples of studies showing models of dynamic coding by cell assemblies in behaving rodents and monkeys. We also discuss how the firing correlation of two neurons reflects the firing synchrony among the numerous surrounding neurons that constitute cell assemblies. Second, we review the recent outstanding studies that used the novel method of optogenetics to show causal relationships between cell-assembly activity and behavioral change. Third, we review the most recently developed method of live-cell imaging, which facilitates the simultaneous observation of firings of a large number of neurons in behaving rodents. Currently, all these available methods have both advantages and disadvantages, and no single measurement method can directly and precisely detect the actual activity of cell assemblies. The best strategy is to combine the available methods and utilize each of their advantages with the technique of operant conditioning of multiple-task behaviors in animals and, if necessary, with brain–machine interface technology to verify the accuracy of neural information detected as cell-assembly activity.

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Pharmacogenetic reactivation of the original engram evokes an extinguished fear memory

Cited by 17 publications

References 37 publications

Memory engrams: Recalling the past and imagining the future

Memory engrams: Recalling the past and imagining the future

Spatial Memory Engram in the Mouse Retrosplenial Cortex

Multiple Approaches to the Investigation of Cell Assembly in Memory Research—Present and Future

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