The role of neuronal excitability, allocation to an engram and memory linking in the behavioral generation of a false memory in mice

Lau, Jocelyn; Rashid, Asim J.; Jacob, Alexander D.; Frankland, Paul W.; Schacter, Daniel L.; Josselyn, Sheena A.

doi:10.1016/j.nlm.2020.107284

Cited by 28 publications

(34 citation statements)

References 58 publications

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“…9–10). This is in contrast with the literature where a critical role for intrinsic excitability has been postulated in reducing the threshold for plasticity induction and in individual neurons being recruited as engram cells for a new context (Schmidt-Hieber et al, 2004; Ge et al, 2007; Yiu et al, 2014; Park et al, 2016; Josselyn and Frankland, 2018; Lodge and Bischofberger, 2019; Pignatelli et al, 2019; Josselyn and Tonegawa, 2020; Lau et al, 2020; Huckleberry and Shansky, 2021). How do we reconcile these observations?…”

Section: Resultscontrasting

confidence: 79%

“…7, 9–10), quantitative introduction of structural heterogeneities allows the consequent intrinsic excitability changes to impose strong constraints on the synaptic plasticity profiles. In other words, although DG granule cells are endowed with considerable baseline heterogeneities, the introduction of an immature population through adult neurogenesis is essential for these neurons to be specifically recruited in a new context during engram formation (Schmidt-Hieber et al, 2004; Yiu et al, 2014; Park et al, 2016; Josselyn and Frankland, 2018; Lodge and Bischofberger, 2019; Pignatelli et al, 2019; Josselyn and Tonegawa, 2020; Lau et al, 2020; Huckleberry and Shansky, 2021).…”

Section: Resultsmentioning

confidence: 99%

“…Although such plasticity heterogeneity has typically been overlooked in analyzing the impact of plasticity protocols, a growing body of experimental evidence has identified crucial roles for plasticity heterogeneity in neural encoding and storage. Specifically, the ability of neurons and synapses to undergo differential plasticity is critical for context-specific recruitment/allocation of a subset of neurons and synapses during encoding processes (Schmidt-Hieber et al, 2004; Ge et al, 2007; Dieni et al, 2013; Aimone et al, 2014; Yiu et al, 2014; Park et al, 2016; Josselyn and Frankland, 2018; Lodge and Bischofberger, 2019; Pignatelli et al, 2019; Josselyn and Tonegawa, 2020; Lau et al, 2020; Huckleberry and Shansky, 2021). The lack of plasticity heterogeneity would result in a scenario where all neurons and synapses undergo similar amount of plasticity for any given context, thus erasing the possibility of sparse and context-specific recruitment of neural resources.…”

Section: Introductionmentioning

confidence: 99%

“…Despite these well-recognized roles of plasticity heterogeneity in context-specific resource allocation, the mechanisms underlying these heterogeneities have not been assessed. Furthermore, although there are postulates and lines of evidence for heterogeneities in intrinsic excitability playing a role in determining selective resource allocation (Schmidt-Hieber et al, 2004; Ge et al, 2007; Dieni et al, 2013; Aimone et al, 2014; Yiu et al, 2014; Park et al, 2016; Josselyn and Frankland, 2018; Lodge and Bischofberger, 2019; Pignatelli et al, 2019; Josselyn and Tonegawa, 2020; Lau et al, 2020; Huckleberry and Shansky, 2021), the quantitative link between such cellular-scale heterogeneities and plasticity heterogeneity has not been assessed.…”

Section: Introductionmentioning

confidence: 99%

“…Third, these intrinsic and plasticity heterogeneities are further amplified by the expression of adult neurogenesis, resulting in immature neurons that manifest increased excitability, reduced synaptic connectivity, lesser dendritic arborization, and hyperplasticity that translates to lower threshold for plasticity induction (Schmidt-Hieber et al, 2004; Ge et al, 2007; Dieni et al, 2013; Aimone et al, 2014; Li et al, 2017; Lodge and Bischofberger, 2019; Huckleberry and Shansky, 2021). Finally, there are lines of evidence for a critical role of plasticity heterogeneity in engram formation, response decorrelation, and resource allocation in the dentate gyrus, with postulates about the role of intrinsic excitability in governing plasticity rules and selective resource allocation (Aimone et al, 2014; Yiu et al, 2014; Park et al, 2016; Josselyn and Frankland, 2018; Lodge and Bischofberger, 2019; Mishra and Narayanan, 2019; Pignatelli et al, 2019; Josselyn and Tonegawa, 2020; Lau et al, 2020; Huckleberry and Shansky, 2021). Together, granule cells allowed us to place plasticity heterogeneity within a strong functionally relevant context of engram formation and response decorrelation, providing an efficient substrate for assessing the impact of well-characterized biophysical and structural heterogeneities on the emergence of plasticity heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

Shridhar

Mishra

Narayanan

2021

Preprint

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Section: Resultscontrasting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

Shridhar

Mishra

Narayanan

2021

Preprint

View full text Add to dashboard Cite

show abstract

Dominant role of adult neurogenesis‐induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

2022

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Neurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, which have been implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic physiologically constrained parametric search to identify the cellular mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We used heterogeneous model populations to ensure that our conclusions were not biased by parametric choices in a single hand-tuned model. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneities in synaptic plasticity profiles obtained with two different induction protocols. However, among the disparate forms of neural-circuit heterogeneities, our analyses demonstrated the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. We found that strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult neurogenesis-induced heterogeneities in neural structure were accounted for. Importantly, our analyses showed that it was not imperative that the manifestation of neural-circuit heterogeneities must translate to heterogeneities in plasticity profiles. Specifically, despite the expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable across all models through synergistic interactions among these heterogeneities. We assessed the parametric combinations required for the manifestation of such degeneracy in the expression of plasticity profiles. We found that immature cells showed physiological plasticity profiles despite receiving afferent inputs with weak synaptic strengths. Thus, the high intrinsic excitability of immature granule cells was sufficient to counterbalance their low excitatory drive in the expression of plasticity profile degeneracy. Together, our analyses demonstrate that disparate forms of neural-circuit heterogeneities could mechanistically drive plasticity heterogeneity, but also caution against treating neural-circuit heterogeneities as proxies for plasticity heterogeneity. Our study emphasizes the need for quantitatively characterizing the relationship between neural-circuit and plasticity heterogeneities across brain regions.Sameera Shridhar and Poonam Mishra contributed equally to this study.

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Distinct engrams control fear and extinction memory

Luft,

Popik,

Gonçalves

et al. 2024

Hippocampus

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Memories are stored in engram cells, which are necessary and sufficient for memory recall. Recalling a memory might undergo reconsolidation or extinction. It has been suggested that the original memory engram is reactivated during reconsolidation so that memory can be updated. Conversely, during extinction training, a new memory is formed that suppresses the original engram. Nonetheless, it is unknown whether extinction creates a new engram or modifies the original fear engram. In this study, we utilized the Daun02 procedure, which uses c‐Fos‐lacZ rats to induce apoptosis of strongly activated neurons and examine whether a new memory trace emerges as a result of a short or long reactivation, or if these processes rely on modifications within the original engram located in the basolateral amygdala (BLA) and infralimbic (IL) cortex. By eliminating neurons activated during consolidation and reactivation, we observed significant impacts on fear memory, highlighting the importance of the BLA engram in these processes. Although we were unable to show any impact when removing the neurons activated after the test of a previously extinguished memory in the BLA, disrupting the IL extinction engram reactivated the aversive memory that was suppressed by the extinction memory. Thus, we demonstrated that the IL cortex plays a crucial role in the network involved in extinction, and disrupting this specific node alone is sufficient to impair extinction behavior. Additionally, our findings indicate that extinction memories rely on the formation of a new memory, supporting the theory that extinction memories rely on the formation of a new memory, whereas the reconsolidation process reactivates the same original memory trace.

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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

Cited by 28 publications

References 58 publications

Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

Dominant role of adult neurogenesis‐induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

Distinct engrams control fear and extinction memory

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