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Synaptic tagging during memory allocation

Key Points

  • Memory allocation to specific neurons (neuronal allocation) and synapses (synaptic allocation) in a neurocircuit is not random; instead, specific mechanisms determine which synapses and neurons go on to store a specific memory.

  • Mechanisms that determine which neurons are recruited to store a given memory include activation of the transcription factor cyclic AMP-dependent element-binding protein (CREB) and increases in neuronal excitability, such as decreases in the afterhyperpolarization.

  • Synaptic tagging and capture, as well as synaptic clustering mechanisms determine which synapses go on to encode a given memory; therefore, they are key mechanisms of memory allocation.

  • In the Review, we introduce an integrated view of neuronal allocation, synaptic tagging and capture, spine clustering and metaplasticity. We propose that these processes reflect different memory allocation mechanisms.

  • We also discuss how deficits in memory allocation could result in cognitive pathologies, such as those associated with ageing or schizophrenia.

Abstract

There is now compelling evidence that the allocation of memory to specific neurons (neuronal allocation) and synapses (synaptic allocation) in a neurocircuit is not random and that instead specific mechanisms, such as increases in neuronal excitability and synaptic tagging and capture, determine the exact sites where memories are stored. We propose an integrated view of these processes, such that neuronal allocation, synaptic tagging and capture, spine clustering and metaplasticity reflect related aspects of memory allocation mechanisms. Importantly, the properties of these mechanisms suggest a set of rules that profoundly affect how memories are stored and recalled.

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Figure 1: Integrating neuronal and synaptic allocation.
Figure 2: Coordinated storage and retrieval of temporally related memories.
Figure 3: Synaptic tagging and capture.
Figure 4: Molecular mechanisms for synaptic clustering and synaptic tagging and capture.

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Acknowledgements

We thank members of the Silva laboratory and P. Golshani's laboratory (see Further information box for the link to the homepage) for discussions that shaped the material and ideas in this Review. The work was supported by grants P50 MH077972, R37 AG013622, and from the Dr. Miriam & Sheldon G. Adelson Medical Research Foundation to A.J.S., 1T32NS058280, 1F31MH092057-01, 2012–13 DYF to T.R., Human Frontiers to M.L.A. and 5 F32 MH097413-02 to D.C.

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Correspondence to Alcino J. Silva.

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Rogerson, T., Cai, D., Frank, A. et al. Synaptic tagging during memory allocation. Nat Rev Neurosci 15, 157–169 (2014). https://doi.org/10.1038/nrn3667

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