Memory Synapses Are Defined by Distinct Molecular Complexes: A Proposal

Overview

Journal Front Synaptic Neurosci

Date 2018 Apr 27

PMID 29695960

Citations 15

Authors

Wayne S Sossin

Affiliations

Soon will be listed here.

Abstract

Synapses are diverse in form and function. While there are strong evidential and theoretical reasons for believing that memories are stored at synapses, the concept of a specialized "memory synapse" is rarely discussed. Here, we review the evidence that memories are stored at the synapse and consider the opposing possibilities. We argue that if memories are stored in an active fashion at synapses, then these memory synapses must have distinct molecular complexes that distinguish them from other synapses. In particular, examples from sensory-motor neuron synapses and synapses on defined engram neurons in rodent models are discussed. Specific hypotheses for molecular complexes that define memory synapses are presented, including persistently active kinases, transmitter receptor complexes and trans-synaptic adhesion proteins.

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References

Chain D, Casadio A, Schacher S, Hegde A, Valbrun M, Yamamoto N . Mechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in Aplysia. Neuron. 1999; 22(1):147-56. DOI: 10.1016/s0896-6273(00)80686-8. View

Casadio A, Martin K, Giustetto M, Zhu H, Chen M, Bartsch D . A transient, neuron-wide form of CREB-mediated long-term facilitation can be stabilized at specific synapses by local protein synthesis. Cell. 1999; 99(2):221-37. DOI: 10.1016/s0092-8674(00)81653-0. View

Xia J, Chung H, Wihler C, Huganir R, Linden D . Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron. 2001; 28(2):499-510. DOI: 10.1016/s0896-6273(00)00128-8. View

Nader K, Schafe G, LeDoux J . The labile nature of consolidation theory. Nat Rev Neurosci. 2001; 1(3):216-9. DOI: 10.1038/35044580. View

Huber K, Roder J, Bear M . Chemical induction of mGluR5- and protein synthesis--dependent long-term depression in hippocampal area CA1. J Neurophysiol. 2001; 86(1):321-5. DOI: 10.1152/jn.2001.86.1.321. View

Kandel E . The molecular biology of memory storage: a dialogue between genes and synapses. Science. 2001; 294(5544):1030-8. DOI: 10.1126/science.1067020. View

Grosshans D, Clayton D, Coultrap S, Browning M . LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1. Nat Neurosci. 2001; 5(1):27-33. DOI: 10.1038/nn779. View

Ling D, Benardo L, Serrano P, Blace N, Kelly M, Crary J . Protein kinase Mzeta is necessary and sufficient for LTP maintenance. Nat Neurosci. 2002; 5(4):295-6. DOI: 10.1038/nn829. View

Wainwright M, Zhang H, Byrne J, Cleary L . Localized neuronal outgrowth induced by long-term sensitization training in aplysia. J Neurosci. 2002; 22(10):4132-41. PMC: 6757634. DOI: 20026347. View

10.

Martin K, Kosik K . Synaptic tagging -- who's it?. Nat Rev Neurosci. 2002; 3(10):813-20. DOI: 10.1038/nrn942. View

11.

Trachtenberg J, Chen B, Knott G, Feng G, Sanes J, Welker E . Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature. 2002; 420(6917):788-94. DOI: 10.1038/nature01273. View

12.

Metzler M, Li B, Gan L, Georgiou J, Gutekunst C, Wang Y . Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking. EMBO J. 2003; 22(13):3254-66. PMC: 165658. DOI: 10.1093/emboj/cdg334. View

13.

Hernandez A, Blace N, Crary J, Serrano P, Leitges M, Libien J . Protein kinase M zeta synthesis from a brain mRNA encoding an independent protein kinase C zeta catalytic domain. Implications for the molecular mechanism of memory. J Biol Chem. 2003; 278(41):40305-16. DOI: 10.1074/jbc.M307065200. View

14.

Ehrlich I, Malinow R . Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci. 2004; 24(4):916-27. PMC: 6729816. DOI: 10.1523/JNEUROSCI.4733-03.2004. View

15.

Marinesco S, Kolkman K, Carew T . Serotonergic modulation in aplysia. I. Distributed serotonergic network persistently activated by sensitizing stimuli. J Neurophysiol. 2004; 92(4):2468-86. DOI: 10.1152/jn.00209.2004. View

16.

Cull-Candy S, Leszkiewicz D . Role of distinct NMDA receptor subtypes at central synapses. Sci STKE. 2004; 2004(255):re16. DOI: 10.1126/stke.2552004re16. View

17.

Holtmaat A, Trachtenberg J, Wilbrecht L, Shepherd G, Zhang X, Knott G . Transient and persistent dendritic spines in the neocortex in vivo. Neuron. 2005; 45(2):279-91. DOI: 10.1016/j.neuron.2005.01.003. View

18.

Serrano P, Yao Y, Sacktor T . Persistent phosphorylation by protein kinase Mzeta maintains late-phase long-term potentiation. J Neurosci. 2005; 25(8):1979-84. PMC: 6726070. DOI: 10.1523/JNEUROSCI.5132-04.2005. View

19.

Lu W, Ziff E . PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron. 2005; 47(3):407-21. DOI: 10.1016/j.neuron.2005.07.006. View

20.

Prybylowski K, Chang K, Sans N, Kan L, Vicini S, Wenthold R . The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Neuron. 2005; 47(6):845-57. PMC: 1350965. DOI: 10.1016/j.neuron.2005.08.016. View