The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Susumu Tonegawa - One of the best experts on this subject based on the ideXlab platform.
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Memory Engrams: Recalling the past and imagining the future
Science (New York N.Y.), 2020Co-Authors: Sheena A. Josselyn, Susumu TonegawaAbstract: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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Engram Cell Excitability State Determines the Efficacy of Memory Retrieval.
Neuron, 2018Co-Authors: Michele Pignatelli, Lillian M. Smith, Dheeraj S. Roy, Tomas J Ryan, Shruti Muralidhar, Chanel Lovett, Susumu TonegawaAbstract:Animals need to optimize the efficacy of memory retrieval to adapt to environmental circumstances for survival. The recent development of memory Engram labeling technology allows a precise investigation of the processes associated with the recall of a specific memory. Here, we show that Engram cell excitability is transiently increased following memory reactivation. This short-term increase of Engram excitability enhances the subsequent retrieval of specific memory content in response to cues and is manifest in the animal's ability to recognize contexts more precisely and more effectively. These results reveal a hitherto unknown transient enhancement of context recognition based on the plasticity of Engram cell excitability. They also suggest that recall of a contextual memory is influenced by previous but recent activation of the same Engram. The state of excitability of Engram cells mediates differential behavioral outcomes upon memory retrieval and may be crucial for survival by promoting adaptive behavior.
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Silent memory Engrams as the basis for retrograde amnesia.
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: Dheeraj S. Roy, Lillian M. Smith, Shruti Muralidhar, Susumu TonegawaAbstract:Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory Engrams). Memory Engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These Engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of Engrams "silent Engrams" and the cells bearing them "silent Engram cells." The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes. Here, we show that the full-fledged optogenetic recall persists at least 8 d after learning under protein synthesis inhibition-induced amnesia. This long-term retention of memory information correlates with equally persistent retention of functional Engram cell-to-Engram cell connectivity. Furthermore, inactivation of the connectivity of Engram cell ensembles with its downstream counterparts, but not upstream ones, prevents optogenetic memory recall. Consistent with the previously reported lack of retention of augmented synaptic strength and reduced spine density in silent Engram cells, optogenetic memory recall under amnesia is stimulation strength-dependent, with low-power stimulation eliciting only partial recall. Finally, the silent Engram cells can be converted to active Engram cells by overexpression of α-p-21-activated kinase 1, which increases spine density in Engram cells. These results indicate that memory information is retained in a form of silent Engram under protein synthesis inhibition-induced retrograde amnesia and support the hypothesis that memory is stored as the specific connectivity between Engram cells.
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manipulating memory in space and time
Current opinion in behavioral sciences, 2017Co-Authors: Susumu TonegawaAbstract:One of the most fascinating aspects of an animal’s brain is its ability to acquire new information from experience and retain this information over time as memory. The search for physical correlates of memory, the memory Engram, has been a longstanding endeavor in modern neurobiology. Recent advances in transgenic and optogenetic tools have enabled the identification, visualization, and manipulations of natural, sensory-evoked, Engram cells for a specific memory residing in specific brain regions. These studies are paving the way not only to understand memory mechanisms in unprecedented detail, but also to repair the abnormal state of mind associated with memory by engineering.
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Engrams and circuits crucial for systems consolidation of a memory
Science, 2017Co-Authors: Takashi Kitamura, Teruhiro Okuyama, Mark D. Morrissey, Lillian M. Smith, Dheeraj S. Roy, Roger L. Redondo, Sachie K Ogawa, Susumu TonegawaAbstract:Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the Engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory Engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala. After their generation, the prefrontal Engram cells, with support from hippocampal memory Engram cells, became functionally mature with time. Whereas hippocampal Engram cells gradually became silent with time, Engram cells in the basolateral amygdala, which were necessary for fear memory, were maintained. Our data provide new insights into the functional reorganization of Engrams and circuits underlying systems consolidation of memory.
Dheeraj S. Roy - One of the best experts on this subject based on the ideXlab platform.
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brain wide mapping of contextual fear memory Engram ensembles supports the dispersed Engram complex hypothesis
bioRxiv, 2019Co-Authors: Dheeraj S. Roy, Sachie K Ogawa, Younggyun Park, Jae H Cho, Heejin Choi, Lee Kamensky, Jared Martin, Kwanghun ChungAbstract:GRAPHICAL ABSTRACT SUMMARY Neuronal ensembles that hold specific memory (memory Engrams) have been identified in the hippocampus, amygdala, and cortex. It has been hypothesized that Engrams for a specific memory are distributed among multiple brain regions that are functionally connected. Here, we report the hitherto most extensive Engram map for contextual fear memory by characterizing activity-tagged neurons in 409 regions using SHIELD-based tissue phenotyping. The mapping was aided by a novel Engram index, which identified cFos+ brain regions holding Engrams with a high probability. Optogenetic manipulations confirmed previously known Engrams and revealed new Engrams. Many of these Engram holding-regions were functionally connected to the CA1 or amygdala Engrams. Simultaneous chemogenetic reactivation of multiple Engrams, which mimics natural memory recall, conferred a greater level of memory recall than reactivation of a single Engram ensemble. Overall, our study supports the hypothesis that a memory is stored in functionally connected Engrams distributed across multiple brain regions.
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Engram Cell Excitability State Determines the Efficacy of Memory Retrieval.
Neuron, 2018Co-Authors: Michele Pignatelli, Lillian M. Smith, Dheeraj S. Roy, Tomas J Ryan, Shruti Muralidhar, Chanel Lovett, Susumu TonegawaAbstract:Animals need to optimize the efficacy of memory retrieval to adapt to environmental circumstances for survival. The recent development of memory Engram labeling technology allows a precise investigation of the processes associated with the recall of a specific memory. Here, we show that Engram cell excitability is transiently increased following memory reactivation. This short-term increase of Engram excitability enhances the subsequent retrieval of specific memory content in response to cues and is manifest in the animal's ability to recognize contexts more precisely and more effectively. These results reveal a hitherto unknown transient enhancement of context recognition based on the plasticity of Engram cell excitability. They also suggest that recall of a contextual memory is influenced by previous but recent activation of the same Engram. The state of excitability of Engram cells mediates differential behavioral outcomes upon memory retrieval and may be crucial for survival by promoting adaptive behavior.
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Silent memory Engrams as the basis for retrograde amnesia.
Proceedings of the National Academy of Sciences of the United States of America, 2017Co-Authors: Dheeraj S. Roy, Lillian M. Smith, Shruti Muralidhar, Susumu TonegawaAbstract:Recent studies identified neuronal ensembles and circuits that hold specific memory information (memory Engrams). Memory Engrams are retained under protein synthesis inhibition-induced retrograde amnesia. These Engram cells can be activated by optogenetic stimulation for full-fledged recall, but not by stimulation using natural recall cues (thus, amnesia). We call this state of Engrams "silent Engrams" and the cells bearing them "silent Engram cells." The retention of memory information under amnesia suggests that the time-limited protein synthesis following learning is dispensable for memory storage, but may be necessary for effective memory retrieval processes. Here, we show that the full-fledged optogenetic recall persists at least 8 d after learning under protein synthesis inhibition-induced amnesia. This long-term retention of memory information correlates with equally persistent retention of functional Engram cell-to-Engram cell connectivity. Furthermore, inactivation of the connectivity of Engram cell ensembles with its downstream counterparts, but not upstream ones, prevents optogenetic memory recall. Consistent with the previously reported lack of retention of augmented synaptic strength and reduced spine density in silent Engram cells, optogenetic memory recall under amnesia is stimulation strength-dependent, with low-power stimulation eliciting only partial recall. Finally, the silent Engram cells can be converted to active Engram cells by overexpression of α-p-21-activated kinase 1, which increases spine density in Engram cells. These results indicate that memory information is retained in a form of silent Engram under protein synthesis inhibition-induced retrograde amnesia and support the hypothesis that memory is stored as the specific connectivity between Engram cells.
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Engrams and circuits crucial for systems consolidation of a memory
Science, 2017Co-Authors: Takashi Kitamura, Teruhiro Okuyama, Mark D. Morrissey, Lillian M. Smith, Dheeraj S. Roy, Roger L. Redondo, Sachie K Ogawa, Susumu TonegawaAbstract:Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the Engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory Engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala. After their generation, the prefrontal Engram cells, with support from hippocampal memory Engram cells, became functionally mature with time. Whereas hippocampal Engram cells gradually became silent with time, Engram cells in the basolateral amygdala, which were necessary for fear memory, were maintained. Our data provide new insights into the functional reorganization of Engrams and circuits underlying systems consolidation of memory.
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In Search of Engram Cells
Learning and Memory: A Comprehensive Reference, 2017Co-Authors: Dheeraj S. Roy, Susumu TonegawaAbstract:One of the most fascinating aspects of an animal's brain is its ability to acquire new information from experience and retain this information over time as memory. The search for physical correlates of memory, the memory Engram, has been a long-standing question in modern neurobiology. Recent advances in transgenics and optogenetic tools have enabled the identification, visualization, and manipulation of natural, sensory-evoked, Engram ensembles unique to individual brain regions, and specific learning events. We suggest that these recent studies are paving the way not only to understand memory mechanisms in unprecedented detail but also to engineer the memory-mediated state of mind and behaviors.
Minoru Saitoe - One of the best experts on this subject based on the ideXlab platform.
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Long-Term Memory Engram Cells Are Established by c-Fos/CREB Transcriptional Cycling.
Cell reports, 2018Co-Authors: Tomoyuki Miyashita, Emi Kikuchi, Junjiro Horiuchi, Minoru SaitoeAbstract:Training-dependent increases in c-fos have been used to identify Engram cells encoding long-term memories (LTMs). However, the interaction between transcription factors required for LTM, including CREB and c-Fos, and activating kinases such as phosphorylated ERK (pERK) in the establishment of memory Engrams has been unclear. Formation of LTM of an aversive olfactory association in flies requires repeated training trials with rest intervals between trainings. Here, we find that prolonged rest interval-dependent increases in pERK induce transcriptional cycling between c-Fos and CREB in a subset of KCs in the mushroom bodies, where olfactory associations are made and stored. Preexisting CREB is required for initial c-fos induction, while c-Fos is required later to increase CREB expression. Blocking or activating c-fos-positive Engram neurons inhibits memory recall or induces memory-associated behaviors. Our results suggest that c-Fos/CREB cycling defines LTM Engram cells required for LTM.
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long term memory Engram cells are established by c fos creb transcriptional cycling
Cell Reports, 2018Co-Authors: Tomoyuki Miyashita, Emi Kikuchi, Junjiro Horiuchi, Minoru SaitoeAbstract:Training-dependent increases in c-fos have been used to identify Engram cells encoding long-term memories (LTMs). However, the interaction between transcription factors required for LTM, including CREB and c-Fos, and activating kinases such as phosphorylated ERK (pERK) in the establishment of memory Engrams has been unclear. Formation of LTM of an aversive olfactory association in flies requires repeated training trials with rest intervals between trainings. Here, we find that prolonged rest interval-dependent increases in pERK induce transcriptional cycling between c-Fos and CREB in a subset of KCs in the mushroom bodies, where olfactory associations are made and stored. Preexisting CREB is required for initial c-fos induction, while c-Fos is required later to increase CREB expression. Blocking or activating c-fos-positive Engram neurons inhibits memory recall or induces memory-associated behaviors. Our results suggest that c-Fos/CREB cycling defines LTM Engram cells required for LTM.
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Long-Term Memory Engram Cells Are Established by c-Fos/CREB Transcriptional Cycling
Elsevier, 2018Co-Authors: Tomoyuki Miyashita, Emi Kikuchi, Junjiro Horiuchi, Minoru SaitoeAbstract:Summary: Training-dependent increases in c-fos have been used to identify Engram cells encoding long-term memories (LTMs). However, the interaction between transcription factors required for LTM, including CREB and c-Fos, and activating kinases such as phosphorylated ERK (pERK) in the establishment of memory Engrams has been unclear. Formation of LTM of an aversive olfactory association in flies requires repeated training trials with rest intervals between trainings. Here, we find that prolonged rest interval-dependent increases in pERK induce transcriptional cycling between c-Fos and CREB in a subset of KCs in the mushroom bodies, where olfactory associations are made and stored. Preexisting CREB is required for initial c-fos induction, while c-Fos is required later to increase CREB expression. Blocking or activating c-fos-positive Engram neurons inhibits memory recall or induces memory-associated behaviors. Our results suggest that c-Fos/CREB cycling defines LTM Engram cells required for LTM. : Long-term memory (LTM) requires transcription factors, including CREB and c-Fos. Miyashita et al. show that spaced training, which induces LTM, activates c-Fos/CREB cycling, where increases in c-Fos require CREB and increases in CREB require c-Fos. c-Fos/CREB cycling defines LTM Engram cells, and modulating the activity of these cells alters memory-associated behaviors. Keywords: long-term memory, CREB, c-fos, spacing effect, MAPK, Drosophila, memory Engram, transcriptional cyclin
Tomas J Ryan - One of the best experts on this subject based on the ideXlab platform.
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Engram Cell Excitability State Determines the Efficacy of Memory Retrieval.
Neuron, 2018Co-Authors: Michele Pignatelli, Lillian M. Smith, Dheeraj S. Roy, Tomas J Ryan, Shruti Muralidhar, Chanel Lovett, Susumu TonegawaAbstract:Animals need to optimize the efficacy of memory retrieval to adapt to environmental circumstances for survival. The recent development of memory Engram labeling technology allows a precise investigation of the processes associated with the recall of a specific memory. Here, we show that Engram cell excitability is transiently increased following memory reactivation. This short-term increase of Engram excitability enhances the subsequent retrieval of specific memory content in response to cues and is manifest in the animal's ability to recognize contexts more precisely and more effectively. These results reveal a hitherto unknown transient enhancement of context recognition based on the plasticity of Engram cell excitability. They also suggest that recall of a contextual memory is influenced by previous but recent activation of the same Engram. The state of excitability of Engram cells mediates differential behavioral outcomes upon memory retrieval and may be crucial for survival by promoting adaptive behavior.
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United states of amnesia: rescuing memory loss from diverse conditions
The Company of Biologists, 2018Co-Authors: Clara Ortega-de San Luis, Tomas J RyanAbstract:Amnesia – the loss of memory function – is often the earliest and most persistent symptom of dementia. It occurs as a consequence of a variety of diseases and injuries. These include neurodegenerative, neurological or immune disorders, drug abuse, stroke or head injuries. It has both troubled and fascinated humanity. Philosophers, scientists, physicians and anatomists have all pursued an understanding of how we learn and memorise, and why we forget. In the last few years, the development of memory Engram labelling technology has greatly impacted how we can experimentally study memory and its disorders in animals. Here, we present a concise discussion of what we have learned about amnesia through the manipulation of Engrams, and how we may use this knowledge to inform novel treatments of amnesia
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What is memory? The present state of the Engram
BMC biology, 2016Co-Authors: Mu-ming Poo, Michele Pignatelli, Susumu Tonegawa, Tomas J Ryan, Tobias Bonhoeffer, Kelsey C. Martin, Andrii Rudenko, Li-huei Tsai, Richard W. Tsien, Gordon FishellAbstract:The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of the Engram, lasting connections in the brain that result from simultaneous “excitations”, whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the Engram means today.
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memory retrieval by activating Engram cells in mouse models of early alzheimer s disease
Nature, 2016Co-Authors: Dheeraj S. Roy, Michele Pignatelli, Susumu Tonegawa, Tomas J Ryan, Autumn Arons, Teryn MitchellAbstract:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD 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 AD, 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 used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus Engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus Engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus 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 the early stages of AD.
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Memory retrieval by activating Engram cells in mouse models of early Alzheimer’s disease
Nature, 2016Co-Authors: Dheeraj S. Roy, Michele Pignatelli, Tomas J Ryan, Autumn Arons, Teryn I. Mitchell, Susumu TonegawaAbstract:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD 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 AD, 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 used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus Engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus Engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus 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 the early stages of AD.
Sheena A. Josselyn - One of the best experts on this subject based on the ideXlab platform.
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The role of neuronal excitability, allocation to an Engram and memory linking in the behavioral generation of a false memory in mice.
Neurobiology of learning and memory, 2020Co-Authors: Jocelyn M.h. Lau, Asim J Rashid, Paul W. Frankland, Alexander D. Jacob, Daniel L. Schacter, Sheena A. JosselynAbstract:Abstract Memory is a constructive, not reproductive, process that is prone to errors. Errors in memory, though, may originate from normally adaptive memory processes. At the extreme of memory distortion is falsely “remembering” an event that did not occur. False memories are well-studied in cognitive psychology, but have received relatively less attention in neuroscience. Here, we took advantage of mechanistic insights into how neurons are allocated or recruited into an Engram (memory trace) to generate a false memory in mice using only behavioral manipulations. At the time of an event, neurons compete for allocation to an Engram supporting the memory for this event; neurons with higher excitability win this competition (Han et al., 2007). Even after the event, these allocated “Engram neurons” remain temporarily (~6 h) more excitable than neighboring neurons. Should a similar event occur in this 6 h period of heightened Engram neuron excitability, an overlapping population of neurons will be co-allocated to this second Engram, which serves to functionally link the two memories (Rashid et al., 2016). Here, we applied this principle of co-allocation and found that mice develop a false fear memory to a neutral stimulus if exposed to this stimulus shortly (3 h), but not a longer time (24 h), after cued fear conditioning. Similar to co-allocation, the generation of this false memory depended on the post-training excitability of Engram neurons such that these neurons remained more excitable during exposure to the neutral stimulus at 3 h but not 24 h. Optogenetically silencing Engram neurons 3 h after cued fear conditioning impaired formation of a false fear memory to the neutral stimulus, while optogenetically activating Engram neurons 24 h after cued fear conditioning created a false fear memory. These results suggest that some false memories may originate from normally adaptive mnemonic processes such as neuronal excitability-dependent allocation and memory linking.
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A time-dependent role for the transcription factor CREB in neuronal allocation to an Engram underlying a fear memory revealed using a novel in vivo optogenetic tool to modulate CREB function
Neuropsychopharmacology, 2020Co-Authors: Albert Park, Asim J Rashid, Paul W. Frankland, Sungmo Park, Alexander D. Jacob, Brandon J. Walters, Jung Hoon Jung, G. Andrew Woolley, Sheena A. JosselynAbstract:The internal representation of an experience is thought to be encoded by long-lasting physical changes to the brain (“Engrams”) . Previously, we and others showed within the lateral amygdala (LA), a region critical for auditory conditioned fear, eligible neurons compete against one other for allocation to an Engram. Neurons with relatively higher function of the transcription factor CREB were more likely to be allocated to the Engram. In these studies, though, CREB function was artificially increased for several days before training. Precisely when increased CREB function is important for allocation remains an unanswered question. Here, we took advantage of a novel optogenetic tool (opto-DN-CREB) to gain spatial and temporal control of CREB function in freely behaving mice. We found increasing CREB function in a small, random population of LA principal neurons in the minutes, but not 24 h, before training was sufficient to enhance memory, likely because these neurons were preferentially allocated to the underlying Engram. However, similarly increasing CREB activity in a small population of random LA neurons immediately after training disrupted subsequent memory retrieval, likely by disrupting the precise spatial and temporal patterns of offline post-training neuronal activity and/or function required for consolidation. These findings reveal the importance of the timing of CREB activity in regulating allocation and subsequent memory retrieval, and further, highlight the potential of optogenetic approaches to control protein function with temporal specificity in behaving animals.
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Memory Engrams: Recalling the past and imagining the future
Science (New York N.Y.), 2020Co-Authors: Sheena A. Josselyn, Susumu TonegawaAbstract: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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The neurobiological foundation of memory retrieval
Nature Neuroscience, 2019Co-Authors: Paul W. Frankland, Sheena A. Josselyn, Stefan KöhlerAbstract:Memory retrieval involves interactions between internal or external cues and stored Engrams. Identification of Engrams in mice permits examination of these interactions at the level of neural ensembles. This review highlights emerging findings. Memory retrieval involves the interaction between external sensory or internally generated cues and stored memory traces (or Engrams) in a process termed ‘ecphory’. While ecphory has been examined in human cognitive neuroscience research, its neurobiological foundation is less understood. To the extent that ecphory involves ‘reawakening’ of Engrams, leveraging recently developed technologies that can identify and manipulate Engrams in rodents provides a fertile avenue for examining retrieval at the level of neuronal ensembles. Here we evaluate emerging neuroscientific research of this type, using cognitive theory as a guiding principle to organize and interpret initial findings. Our Review highlights the critical interaction between Engrams and retrieval cues (environmental or artificial) for memory accessibility and retrieval success. These findings also highlight the intimate relationship between the mechanisms important in forming Engrams and those important in their recovery, as captured in the cognitive notion of ‘encoding specificity’. Finally, we identify several questions that currently remain unanswered.
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Neuronal competition: microcircuit mechanisms define the sparsity of the Engram.
Current opinion in neurobiology, 2018Co-Authors: Priyanka Rao-ruiz, Steven A. Kushner, Sheena A. JosselynAbstract:Extensive work in computational modeling has highlighted the advantages for employing sparse yet distributed data representation and storage Kanerva (1998), properties that extend to neuronal networks encoding mnemonic information (memory traces or Engrams). While neurons that participate in an Engram are distributed across multiple brain regions, within each region, the cellular sparsity of the mnemonic representation appears to be quite fixed. Although technological advances have enabled significant progress in identifying and manipulating Engrams, relatively little is known about the region-dependent microcircuit rules governing the cellular sparsity of an Engram. Here we review recent studies examining the mechanisms that help shape Engram architecture and examine how these processes may regulate memory function. We speculate that countervailing forces in local microcircuits contribute to the generation and maintenance of Engrams and discuss emerging questions regarding how Engrams are formed, stored and used.