Creating a False Memory in the Hippocampus

Ramirez, Steve; Liu, Xu; Lin, Pei-Ann; Suh, Junghyup; Pignatelli, Michele; Redondo, Roger L.; Ryan, Tomás J.; Tonegawa, Susumu

doi:10.1126/science.1239073

Cited by 810 publications

(736 citation statements)

References 29 publications

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“…DG neurons with increased excitability are preferentially recruited to an engram, as selectively disrupting the activity of these neurons (and not an equivalent number of random DG neurons) before testing disrupts expression of that contextual memory. This result and other similar studies (Liu et al, 2012;Ramirez et al, 2013) identify neurons allocated to an engram. However, post-learning processes, presumably in neurons allocated to the engram, are thought to be important for successful memory consolidation (Marr, 1971;Buzsáki, 1989;Wilson and McNaughton, 1994;Girardeau et al, 2009;Ego-Stengel and Wilson, 2010;Carr et al, 2011).…”

Section: Inhibition Of a Dg Fear Engram Shortly After Training Disrupsupporting

confidence: 71%

Neuronal Allocation to a Hippocampal Engram

Park

Kramer

Mercaldo

et al. 2016

Neuropsychopharmacol

155

113

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The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation.

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Section: Inhibition Of a Dg Fear Engram Shortly After Training Disrupsupporting

confidence: 71%

Neuronal Allocation to a Hippocampal Engram

Park

Kramer

Mercaldo

et al. 2016

Neuropsychopharmacol

155

113

View full text Add to dashboard Cite

show abstract

“…By combining immediate early gene analysis and optogenetic technique, Tonegawa and colleagues identified neurons that are recruited by learning processes and whose activation leads to memory retrieval (Ramirez et al 2013;Redondo et al 2014;Tonegawa et al 2015). These authors propose that "enhanced engram cell-specific synaptic strength is crucial for the retrievability of particular memory engrams, while the memory information content itself is encoded in a pattern of engram cell ensemble connectivity" (Tonegawa et al 2015).…”

Section: Layer-specific Memory Evoked Activity In the Te2 Cortexmentioning

confidence: 99%

Region- and Layer-Specific Activation of the Higher Order Auditory Cortex Te2 after Remote Retrieval of Fear or Appetitive Memories

et al. 2016

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The auditory cortex is involved in encoding sounds which have acquired an emotional-motivational charge. However, the neural circuitry engaged by emotional memory processes in the auditory cortex is poorly understood. In this study, we investigated the layers and regions that are recruited in the higher order auditory cortex Te2 by a tone previously paired to either fear or appetitive stimuli in rats. By tracking the protein coded by the immediate early gene zif268, we found that fear memory retrieval engages layers II-III in most regions of Te2. These results were neither due to an enhanced fear state nor to fear-evoked motor responses, as they were absent in animals retrieving an olfactory fear memory. These layers were also activated by appetitive auditory memory retrieval. Strikingly, layer IV was recruited by fear, but not appetitive memories, whereas layer V activity was related to the behavioral responses displayed to the CS.In addition to revealing the layers and regions which are recruited in the Te2 by either fear or appetitive remote memories, our study also shows that the neural circuitry within the Te2 that processes and stores emotional memories varies on the basis of the affective-motivational charge of tones.

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“…Data acquisition used an Axon CNS Digidata 1440A system. MATLAB analysis was performed, as previously described 12 .…”

Section: In Vivo Recordingsmentioning

confidence: 99%

Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

Roy¹,

Arons²,

Mitchell³

et al. 2016

Nature

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474

377

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SummaryAlzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions 1 . Memory decline in early stages of Alzheimer's is mostly limited to episodic memory, for which the hippocampus (HPC) plays a crucial role 2 . However, it has been uncertain whether the observed amnesia in early stages of Alzheimer's is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early Alzheimer's, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are utilized, revealing a retrieval, rather than a storage impairment. Prior to amyloid plaque deposition, the amnesia in these mice is age-dependent 3 -5 , which correlates with a progressive reduction of spine density of hippocampal dentate gyrus (DG) engram cells. We show that optogenetic induction of long-term potentiation (LTP) at perforant path (PP) synapses of DG engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of DG engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in early stages of Alzheimer's disease.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature

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Creating a False Memory in the Hippocampus

Cited by 810 publications

References 29 publications

Neuronal Allocation to a Hippocampal Engram

Neuronal Allocation to a Hippocampal Engram

Region- and Layer-Specific Activation of the Higher Order Auditory Cortex Te2 after Remote Retrieval of Fear or Appetitive Memories

Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

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