Memory Allocation

Frankland, Paul W.; Josselyn, Sheena A.

doi:10.1038/npp.2014.234

Cited by 19 publications

(16 citation statements)

References 6 publications

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“…In these initial studies, CREB was virally overexpressed before training in a small, random subset (~15%) of pyramidal neurons in the lateral amygdala (LA), a structure known to be important in auditory fear conditioning 13,101-103 . Using Arc mRNA expression as a marker of a recently active neuron 80 , it was found that neurons with higher CREB activity at the time of training were more likely, than their neighbours with lower CREB activity, to be active during memory retrieval, suggesting that higher levels of CREB activity mediate allocation to the engram 8,104 . Although this effect was initially described in the LA for auditory fear memory, it has also been observed in the LA during encoding of conditioned taste aver sion 105 and encoding of cocaineconditioned place preference 106 memories, in the insular cortex during Box 3 | Previous attempts to find the engram From a historical perspective, there have been many other examples of attempts to localize to engrams in addition to those described in this Review.…”

Section: Box 2 | Reconsolidation and The Engrammentioning

confidence: 99%

Finding the engram

2015

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Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent 'capture' studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram.

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Section: Box 2 | Reconsolidation and The Engrammentioning

confidence: 99%

Finding the engram

2015

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“…One example comes from studies examining how changes in intrinsic properties of neurons bias their allocation into memory traces (Han et al, 2007;Zhou et al, 2009;Kim et al, 2014;Yiu et al, 2014). In pioneering studies that first instantiated the cellular basis of an engram (Han et al, 2007;Han et al, 2009), it was found that neuronal recruitment into fear engrams could be biased by elevating levels of a transcription factor, cAMP response element-binding protein (CREB), or intrinsic excitability (Rogerson et al, 2014;Frankland and Josselyn, 2015). Thus, in theory, molecular control of integration of adultborn DGCs into existing memory traces may dictate interference to influence memory precision.…”

Section: Re-engineering Intrinsic and Extrinsic Connectivity Of The Dmentioning

confidence: 99%

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

Besnard

Sahay

2015

Neuropsychopharmacol

192

159

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The generalization of fear is an adaptive, behavioral, and physiological response to the likelihood of threat in the environment. In contrast, the overgeneralization of fear, a cardinal feature of posttraumatic stress disorder (PTSD), manifests as inappropriate, uncontrollable expression of fear in neutral and safe environments. Overgeneralization of fear stems from impaired discrimination of safe from aversive environments or discernment of unlikely threats from those that are highly probable. In addition, the time-dependent erosion of episodic details of traumatic memories might contribute to their generalization. Understanding the neural mechanisms underlying the overgeneralization of fear will guide development of novel therapeutic strategies to combat PTSD. Here, we conceptualize generalization of fear in terms of resolution of interference between similar memories. We propose a role for a fundamental encoding mechanism, pattern separation, in the dentate gyrus (DG)-CA3 circuit in resolving interference between ambiguous or uncertain threats and in preserving episodic content of remote aversive memories in hippocampal-cortical networks. We invoke cellular-, circuit-, and systems-based mechanisms by which adult-born dentate granule cells (DGCs) modulate pattern separation to influence resolution of interference and maintain precision of remote aversive memories. We discuss evidence for how these mechanisms are affected by stress, a risk factor for PTSD, to increase memory interference and decrease precision. Using this scaffold we ideate strategies to curb overgeneralization of fear in PTSD.

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“…For instance, the CREB-induced enhancement of neuronal excitability biases the neuronal and synaptic dynamics such that the respective subgroup of neurons is more likely to be involved in the formation of a memory representation (7; 42, 52 ). Furthermore, the dynamics of CREB seem to be time-dependent 32,42,46 . Therefore, the enhancement of CREB can counterbalance heterosynaptic depression for a given period of time and, by this, could enable the formation of overlaps.…”

Section: Discussionmentioning

confidence: 99%

“…These variations could be, aside from noise, enforced experimentally by adapting neuronal parameters in a local group of neurons. Amongst others, several experiments 42,46 indicate that the probability of a group of neurons to become part of a newly formed memory representation can be influenced by changing their excitability pharmacologically (e.g., by varying the CREB concentration). We reproduced such manipulations in the model by adapting the neuronal excitability of a group of neurons accordingly and analysing the data similar to experiments (see Materials and Methods).…”

Section: Modelling Experimental Findings Of Competition-based Memory mentioning

confidence: 99%

The interplay of synaptic plasticity and scaling enables self-organized formation and allocation of multiple memory representations

Auth

Nachstedt

Tetzlaff

2018

Preprint

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It is commonly assumed that memories about experienced stimuli are represented in the brain by groups of highly interconnected neurons called Hebbian cell assemblies. This requires allocating and storing information in the neural circuitry, which happens through synaptic weight adaptation. It remains, however, largely unknown how memory allocation and storage can be achieved and coordinated to allow for a faithful representation of multiple memories without disruptive interference between them. In this theoretical study, we show that the interplay between conventional Hebbian synaptic plasticity and homeostatic synaptic scaling organizes synaptic weight adaptations such that, on the one hand, a new stimulus forms a new memory while, on the other hand, different stimuli are assigned to distinct Hebbian cell assemblies. We show that the resulting dynamics can reproduce experimental in-vivo data focusing on how other neuronal and synaptic factors, such as neuronal excitability and network connectivity, influence memory formation. Thus, the here presented model suggests that a few fundamental synaptic mechanisms may suffice to implement memory allocation and storage in neural circuitry. Author summaryThe survival in a changing environment requires the reliable learning, storage, and organization of relevant stimuli in the neuronal circuit. This theoretical work addresses the important issue of how a neuronal circuit coordinates the learning-related synaptic adaptations to properly assign new information to groups of neurons and to form long-lasting memory representations of multiple stimuli. We show that this requires only three synaptic properties -homosynaptic potentiation paired with heterosynaptic depression both driven by the postsynaptic activity level. These properties naturally arise from the generic interplay between conventional Hebbian synaptic plasticity and homeostatic synaptic scaling. Therefore, this study shows that the complex processes of memory allocation and storage can be attributed to ubiquitous synaptic mechanisms in the neural circuitry.

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Memory Allocation

Cited by 19 publications

References 6 publications

Finding the engram

Finding the engram

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

The interplay of synaptic plasticity and scaling enables self-organized formation and allocation of multiple memory representations

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