Chapter 7 ‘Synaptic tagging’ and ‘cross-tagging’ and related associative reinforcement processes of functional plasticity as the cellular basis for memory formation
Abstract
We focus on new properties of cellular and network processes of memory formation involving 'synaptic tagging' and 'cross-tagging' during long-term potentiation (LTP) and long-term depression (LTD) as well as associative heterosynaptic interactions, the latter of which are characterized by a time-window of about 1h. About 20 years ago we showed for the first time that the maintenance of LTP, like memory storage, depends on intact protein synthesis and thus consists of at least two temporal phases. Later, similar properties for LTD were shown by our own and other laboratories. Here we describe the requirements for the induction of the transient early-LTP/LTD and of the protein synthesis-dependent late-LTP/LTD. Late-LTP/LTD depend on the associative activation of heterosynaptic inputs, i.e. the synergistic activation of glutamatergic and modulatory reinforcing inputs within specific, effective time-windows during their induction. The induction of late-LTP/LTD is characterized by novel, late-associative properties such as 'synaptic tagging', 'cross-tagging' and 'late-associative reinforcement'. All of these phenomena require the associative setting of synaptic tags as well as the availability of plasticity-related proteins (PRPs) and they are restricted to functional dendritic compartments, in general. 'Synaptic tagging' guarantees input specificity, 'cross-tagging' determines the interaction between LTP and LTD in a neuron, and thus both are required for the specific processing of afferent signals for the establishment of late-LTP/LTD. 'Late-associative reinforcement' describes a process where early-LTP/LTD by the co-activation of modulatory inputs can be transformed into late-LTP/LTD in activated synapses where a tag is set. Recent experiments in the freely moving rat revealed a number of modulatory brain structures involved in the transformation of early-plasticity events into long-lasting ones. Further to this, we have characterized time-windows and activation patterns to be effective in the reinforcement process. Studies using a combined electrophysiological and behavioural approach revealed the physiological relevance of these reinforcement processes, which is also supported by fMRI studies in humans, which led to the hypothesis outlined here on cellular and system memory-formation by late-associative heterosynaptic interactions at the cellular level during functional plasticity events.
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Cholinergic and noradrenergic projections to the medial temporal lobe can also modulate LTP and long-term memory.
“LCholinergic [136] and noradrenergic [10] projections to MTL can also modulate LTP and long-term memory.”
From A neoHebbian framework for episodic memory; role of dopamine-dependent late LTP (2011) · cites this paper as [10]
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Self-citationReymann, K. G., Frey, U., & Matthies, H. K. (1988) · Springer eBooks · doi:10.1007/978-3-642-73202-7_37 · Cited by 15 · see citing works
Posttetanic Long‐Term Potentiation in Rat Dentate Area Increases Postsynaptic 411B Immunoreactivity
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Long-Term Synaptic Potentiation and Macromolecular Changes in Memory Formation
Matthies, H. K. (1988) · Springer eBooks · doi:10.1007/978-3-642-73202-7_35 · Cited by 7 · see citing works
Hassan, H., Frey, S., & Frey, J. U. (2005) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2005.09.005 · Cited by 6 · see citing works
Self-citationMerchenthaler (1999) · doi:10.1002/(sici)1096-9861(19990111)403:2
Episodic memory, semantic memory, and amnesia
Squire, L. R., & Zola, S. M. (1998) · Hippocampus · doi:10.1002/(sici)1098-1063(1998)8:3
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Pape, H.-C., & Pare, D. (2010) · Physiological Reviews · doi:10.1152/physrev.00037.2009 · Cited by 994 · see citing works
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Behavioral tagging is a general mechanism of long-term memory formation
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Düzel, E., Bunzeck, N., Guitart-Masip, M., & Düzel, S. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.08.006 · Cited by 249 · see citing works
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Moncada, D., Ballarini, F., Martinez, M. C., Frey, J. U., & Viola, H. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104495108 · Cited by 171 · see citing works
Self-citationThe learning of fear extinction
Furini, C., Myskiw, J., & Izquierdo, I. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.10.016 · Cited by 124 · see citing works
Behavioral specifications of reward-associated long-term memory enhancement in humans
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Cassini, L. F., Sierra, R. O., Haubrich, J., Crestani, A. P., Santana, F., de Oliveira Alvares, L., & Quillfeldt, J. A. (2013) · Hippocampus · doi:10.1002/hipo.22149 · Cited by 36 · see citing works
- Authors
- Frey, S., & Frey, J. U.
- Affiliations
- Leibniz Institute for Neurobiology (DE)
- Corresponding author
- Frey, Julietta U.
- Venue
- Progress in brain research
- Publisher
- Elsevier
- Published
- 2008
- Volume
- 169
- Pages
- 117-143
- ISSN
- 0079-6123 (ISSN-L)
- OpenAlex
- W1571281589
- Cited by
- 139
- References
- 122
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 2 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 11 · 2014: 14 · 2013: 12 · 2012: 8
- FWCI
- 16.36
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- synaptic tagging, long-term potentiation, long-term depression, memory formation, glutamatergic input, dendritic compartments, functional plasticity
- MeSH terms
- Animals, Memory, Models, Biological, Neuronal Plasticity, Reinforcement, Psychology, Synapses, Protein Biosynthesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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