Linking Memories across Time via Neuronal and Dendritic Overlaps in Model Neurons with Active Dendrites

Kastellakis, George; Silva, Alcino J.; Poirazi, Panayiota

doi:10.1016/j.celrep.2016.10.015

Cited by 96 publications

(124 citation statements)

References 50 publications

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“…However, only by considering an abstract model, we have been able to derive analytical expressions such that we could find the requirement of the three generic properties yielding the proper formation and 11/17 allocation of memories. Remarkably, the synaptic plasticity processes considered in the detailed models 32,52,53 also imply the three generic properties (i-iii) supporting our findings. Further investigations are required to assess possible differences between different realizations of the three generic properties.…”

Section: Discussionsupporting

confidence: 87%

“…Despite the abstract level of description, the model matches experimental in-vivo data of memory allocation. Other theoretical models match similar experimental data 32,52 ; however, these models are of greater biological detail including more dynamic processes (e.g., short-term plasticity). However, only by considering an abstract model, we have been able to derive analytical expressions such that we could find the requirement of the three generic properties yielding the proper formation and 11/17 allocation of memories.…”

Section: Discussionmentioning

confidence: 66%

“…For a proper allocation of stimuli to their internal representations, the synapses from the neurons encoding the stimulus to the neurons encoding the internal representation have to be adjusted accordingly. Considering only these types of synapses ("feed-forward synapses"), several studies show that long-term synaptic plasticity yields the required adjustments of synaptic weights [28][29][30][31][32][33] such that each stimulus is mapped to its corresponding group of neurons. However, theoretical studies 34,35 , which investigate the formation of input-maps in the visual cortex 36,37 , show that the stable mapping or allocation of stimuli onto a neural circuit requires, in addition to synaptic plasticity, homeostatic mechanisms such as synaptic scaling.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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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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“…mRNAs coding for the voltage‐gated potassium channel subfamilies Kv1, Kv4, Kvβ, the large conductance calcium sensitive potassium channel BK, and G‐protein activated inwardly rectifying potassium channel (GIRK or Kir 3) have been localised to dendrites . It's still early days in our understanding of how intrinsic excitability contributes to memory, but local synthesis of ion channels provides a solution for site‐specific titration of synaptic activation, which in turn will increase the capacity of memory storage .…”

Section: Potassium Channels the Lovable Losers As A Putative Memorymentioning

confidence: 99%

mTOR referees memory and disease through mRNA repression and competition

Raab‐Graham

Niere

2017

FEBS Letters

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Mammalian target of rapamycin (mTOR) activity is required for memory and is dysregulated in disease. Activation of mTOR promotes protein synthesis; however, new studies are demonstrating that mTOR activity also represses the translation of mRNAs. Almost three decades ago, Kandel and colleagues hypothesised that memory was due to the induction of positive regulators and removal of negative constraints. Are these negative constraints repressed mRNAs that code for proteins that block memory formation? Herein, we will discuss the mRNAs coded by putative memory suppressors, how activation/inactivation of mTOR repress protein expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA stability, and translation, and what the possible implications of mRNA repression are to memory and neurodegenerative disorders.

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“…Previous modeling studies of synaptic clustering have focused on different aspects than stimulus feature tuning and its organization. Many implement activity-dependent plasticity operating on slow time scales necessary for long-term memory formation, arguing that clustered configurations encode memories more robustly and efficiently (17,18) , increase a cell's computational capacity (19) and can link multiple memories across extended periods (20) . Spike-timing-dependent plasticity has also been shown to drive clustering -albeit of an unusual nature involving synaptic efficacies -with limited biological relevance (21) .…”

mentioning

confidence: 99%

A unifying framework for synaptic organization on cortical dendrites

Kirchner

Gjorgjieva

2019

Preprint

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Dendritic synaptic inputs are organized into functional clusters with remarkable subcellular precision at the micron level. This organization emerges during early postnatal development through patterned spontaneous activity and manifests both locally where nearby synapses are significantly correlated, and globally with distance to the soma. We propose a biophysically motivated synaptic plasticity model to dissect the mechanistic origins of this organization during development, and elucidate synaptic clustering of different stimulus features in the adult. Our model captures local clustering of orientation in ferret vs. receptive field overlap in mouse visual cortex based on the cortical magnification of visual space. Including a back-propagating action potential explains branch clustering heterogeneity in the ferret, and produces a global retinotopy gradient from soma to dendrite in the mouse. Therefore, our framework suggests that sub-cellular precision in connectivity can already be established in development, and unifies different aspects of synaptic organization across species and scales.Neurons in the developing brain are already precisely connected before sensory organs mature. It is widely accepted that spontaneous activity refines circuit connectivity to mature levels at the scale of single neurons and networks. Recent studies have revealed that spontaneous activity can also establish fine-scale organization of individual synapses within the dendritic arborizations of single neurons (1,2) . One striking example of this organization is functional synaptic clustering: synapses onto dendrites of pyramidal neurons that receive correlated input or encode a common sensory feature are spatially grouped. Synaptic clustering has been observed across brain regions, developmental ages and diverse species from rodent to primate (1-10) and has multiple functional benefits; it compartmentalizes the dendrites of single neurons, enables supra-linear integration of inputs and shapes memory

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Linking Memories across Time via Neuronal and Dendritic Overlaps in Model Neurons with Active Dendrites

Cited by 96 publications

References 50 publications

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

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

mTOR referees memory and disease through mRNA repression and competition

A unifying framework for synaptic organization on cortical dendrites

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