Skip to main content
SpringerLink
Log in

Exploring New Horizons: Synaptic Tagging and Capture Beyond Space and Time

  • Chapter
  • First Online:
Synaptic Tagging and Capture

Abstract

Synaptic tagging and capture (STC) encapsulates how synapses attain persistence in their plasticity through capturing newly synthesized plasticity-related products (PRPs) via their tag. This theory also extends to how synapses exhibit associative properties by capturing PRPs whose synthesis is invoked by another set of synapses. Since its conceptualization, STC has been extensively studied mainly in the Schaffer collateral inputs onto the CA1 neurons within the hippocampus, with implications for the associativity of synaptic properties and in turn memory. Recently, emerging work has explored beyond the CA1 neurons, such as the neighboring CA2 and lateral amygdala. Exploring STC in different neuronal populations reveals different plasticity rules and provides more insight into refining the STC model. Meanwhile, expanding behavioral tagging, the behavioral correlate of STC, beyond initial encoding, also illuminates how STC remains relevant in the reactivation and reconsolidation of memories. This review will share these exciting advancements that examine STC beyond the CA1 space as well as the time of initial encoding.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
eBook
USD 169.00
Price excludes VAT (USA)
Hardcover Book
USD 219.99
Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andersen P, Bliss TV, Skrede KK (1971) Lamellar organization of hippocampal pathways. Exp Brain Res 13:222–238

    Article  CAS  PubMed  Google Scholar 

  • Ballarini F, Moncada D, Martinez MC, Alen N, Viola H (2009) Behavioral tagging is a general mechanism of long-term memory formation. Proc Natl Acad Sci USA 106:14599–14604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benoy A, Dasgupta A, Sajikumar S (2018) Hippocampal area CA2: an emerging modulatory gateway in the hippocampal circuit. Exp Brain Res 236:919–931

    Article  CAS  PubMed  Google Scholar 

  • Benoy A, Wong L-W, Ather N, Sajikumar S (2022) Serotonin facilitates late-associative plasticity via synaptic tagging/cross-tagging and capture at hippocampal CA2 synapses in male rats. Oxford Open Neuroscience 1

    Google Scholar 

  • Beyeler A, Dabrowska J (2020) Neuronal diversity of the amygdala and the bed nucleus of the stria terminalis. Handb Behav Neurosci 26:63–100

    Article  PubMed  PubMed Central  Google Scholar 

  • Bin Ibrahim MZ, Benoy A, Sajikumar S (2022) Long-term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses. FEBS J 289:2176–2201

    Article  CAS  PubMed  Google Scholar 

  • Blair HT, Schafe GE, Bauer EP, Rodrigues SM, LeDoux JE (2001) Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. Learn Mem 8:229–242

    Article  CAS  PubMed  Google Scholar 

  • Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borhegyi Z, Leranth C (1997) Substance P innervation of the rat hippocampal formation. J Comp Neurol 384:41–58

    Article  CAS  PubMed  Google Scholar 

  • Cai DJ, Aharoni D, Shuman T, Shobe J, Biane J et al (2016) A shared neural ensemble links distinct contextual memories encoded close in time. Nature 534:115–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carstens KE, Dudek SM (2019) Regulation of synaptic plasticity in hippocampal area CA2. Curr Opin Neurobiol 54:194–199

    Article  CAS  PubMed  Google Scholar 

  • Carstens KE, Phillips ML, Pozzo-Miller L, Weinberg RJ, Dudek SM (2016) Perineuronal nets suppress plasticity of excitatory synapses on CA2 pyramidal neurons. J Neurosci 36:6312–6320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassini LF, Sierra RO, Haubrich J, Crestani AP, Santana F et al (2013) Memory reconsolidation allows the consolidation of a concomitant weak learning through a synaptic tagging and capture mechanism. Hippocampus 23:931–941

    Article  CAS  PubMed  Google Scholar 

  • Chevaleyre V, Piskorowski RA (2016) Hippocampal area CA2: an overlooked but promising therapeutic target. Trends Mol Med 22:645–655

    Article  PubMed  Google Scholar 

  • Chevaleyre V, Siegelbaum SA (2010) Strong CA2 pyramidal neuron synapses define a powerful disynaptic cortico-hippocampal loop. Neuron 66:560–572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collingridge GL, Peineau S, Howland JG, Wang YT (2010) Long-term depression in the CNS. Nat Rev Neurosci 11:459–473

    Article  CAS  PubMed  Google Scholar 

  • Conway MA (1995) Flashbulb memories. Erlbaum Associates, Hove, p 140

    Google Scholar 

  • Cui Z, Gerfen CR, Young WS 3rd. (2013) Hypothalamic and other connections with dorsal CA2 area of the mouse hippocampus. J Comp Neurol 521:1844–1866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dasgupta A, Baby N, Krishna K, Hakim M, Wong YP et al (2017) Substance P induces plasticity and synaptic tagging/capture in rat hippocampal area CA2. Proc Natl Acad Sci USA 114:E8741–E8E49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dasgupta A, Lim YJ, Kumar K, Baby N, Pang KLK et al (2020) Group III metabotropic glutamate receptors gate long-term potentiation and synaptic tagging/capture in rat hippocampal area CA2. elife 9

    Google Scholar 

  • Dityatev A, Schachner M (2003) Extracellular matrix molecules and synaptic plasticity. Nat Rev Neurosci 4:456–468

    Article  CAS  PubMed  Google Scholar 

  • Donegan ML, Stefanini F, Meira T, Gordon JA, Fusi S, Siegelbaum SA (2020) Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a 22q11.2 microdeletion mouse model. Nat Neurosci 23:1365–1375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drephal C, Schubert M, Albrecht D (2006) Input-specific long-term potentiation in the rat lateral amygdala of horizontal slices. Neurobiol Learn Mem 85:272–282

    Article  PubMed  Google Scholar 

  • Dudek SM, Alexander GM, Farris S (2016) Rediscovering area CA2: unique properties and functions. Nat Rev Neurosci 17:89–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dudek SM, Bear MF (1992) Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc Natl Acad Sci USA 89:4363–4367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunsmoor JE, Murty VP, Davachi L, Phelps EA (2015) Emotional learning selectively and retroactively strengthens memories for related events. Nature 520:345–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eichenbaum H, Yonelinas AP, Ranganath C (2007) The medial temporal lobe and recognition memory. Annu Rev Neurosci 30:123–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fonseca R (2013) Asymmetrical synaptic cooperation between cortical and thalamic inputs to the amygdale. Neuropsychopharmacology 38:2675–2687

    Article  PubMed  PubMed Central  Google Scholar 

  • Fonseca R, Nagerl UV, Morris RG, Bonhoeffer T (2004) Competing for memory: hippocampal LTP under regimes of reduced protein synthesis. Neuron 44:1011–1020

    CAS  PubMed  Google Scholar 

  • Fourcaudot E, Gambino F, Casassus G, Poulain B, Humeau Y, Luthi A (2009) L-type voltage-dependent Ca(2+) channels mediate expression of presynaptic LTP in amygdala. Nat Neurosci 12:1093–1095

    Article  CAS  PubMed  Google Scholar 

  • Frey U, Morris RG (1997) Synaptic tagging and long-term potentiation. Nature 385:533–536

    Article  CAS  PubMed  Google Scholar 

  • Frey U, Morris RG (1998a) Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci 21:181–188

    Article  CAS  PubMed  Google Scholar 

  • Frey U, Morris RG (1998b) Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP. Neuropharmacology 37:545–552

    Article  CAS  PubMed  Google Scholar 

  • Hensler JG (2006) Serotonergic modulation of the limbic system. Neurosci Biobehav Rev 30:203–214

    Article  CAS  PubMed  Google Scholar 

  • Hitti FL, Siegelbaum SA (2014) The hippocampal CA2 region is essential for social memory. Nature 508:88–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang YY, Kandel ER (1998) Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron 21:169–178

    Article  CAS  PubMed  Google Scholar 

  • Humeau Y, Herry C, Kemp N, Shaban H, Fourcaudot E et al (2005) Dendritic spine heterogeneity determines afferent-specific Hebbian plasticity in the amygdala. Neuron 45:119–131

    Article  CAS  PubMed  Google Scholar 

  • Ito HT, Schuman EM (2012) Functional division of hippocampal area CA1 via modulatory gating of entorhinal cortical inputs. Hippocampus 22:372–387

    Article  CAS  PubMed  Google Scholar 

  • Ji RR, Kohno T, Moore KA, Woolf CJ (2003) Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 26:696–705

    Article  CAS  PubMed  Google Scholar 

  • Johansen JP, Cain CK, Ostroff LE, LeDoux JE (2011) Molecular mechanisms of fear learning and memory. Cell 147:509–524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones MW, McHugh TJ (2011) Updating hippocampal representations: CA2 joins the circuit. Trends Neurosci 34:526–535

    Article  CAS  PubMed  Google Scholar 

  • Kandel ER (2001) The molecular biology of memory storage: a dialogue between genes and synapses. Science 294:1030–1038

    Article  CAS  PubMed  Google Scholar 

  • LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184

    Article  CAS  PubMed  Google Scholar 

  • Lee SE, Simons SB, Heldt SA, Zhao M, Schroeder JP et al (2010) RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory. Proc Natl Acad Sci USA 107:16994–16998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee Y, Oh JP, Han JH (2021) Dissociated role of thalamic and cortical input to the lateral amygdala for consolidation of long-term fear memory. J Neurosci 41:9561–9570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehr AB, Kumar A, Tetzlaff C, Hafting T, Fyhn M, Stober TM (2021) CA2 beyond social memory: evidence for a fundamental role in hippocampal information processing. Neurosci Biobehav Rev 126:398–412

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Meloni EG, Carlezon WA Jr, Milad MR, Pitman RK et al (2013) Learning and reconsolidation implicate different synaptic mechanisms. Proc Natl Acad Sci USA 110:4798–4803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Rojas J, de Solis CA, Leroy F, Kandel ER, Siegelbaum SA (2022) A direct lateral entorhinal cortex to hippocampal CA2 circuit conveys social information required for social memory. Neuron 110(1559–72):1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madeira N, Drumond A, Fonseca R (2020) Temporal gating of synaptic competition in the amygdala by cannabinoid receptor activation. Cereb Cortex 30:4064–4075

    Article  PubMed  Google Scholar 

  • Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21

    Article  CAS  PubMed  Google Scholar 

  • Maren S (2005) Synaptic mechanisms of associative memory in the amygdala. Neuron 47:783–786

    Article  CAS  PubMed  Google Scholar 

  • Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711

    Article  CAS  PubMed  Google Scholar 

  • Meira T, Leroy F, Buss EW, Oliva A, Park J, Siegelbaum SA (2018) A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics. Nat Commun 9:4163

    Article  PubMed  PubMed Central  Google Scholar 

  • Moncada D, Viola H (2007) Induction of long-term memory by exposure to novelty requires protein synthesis: evidence for a behavioral tagging. J Neurosci 27:7476–7481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nader K (2015) Reconsolidation and the dynamic nature of memory. Cold Spring Harb Perspect Biol 7:a021782

    Article  PubMed  PubMed Central  Google Scholar 

  • Nader K, Schafe GE, Le Doux JE (2000) Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406:722–726

    Article  CAS  PubMed  Google Scholar 

  • Nakashiba T, Young JZ, McHugh TJ, Buhl DL, Tonegawa S (2008) Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning. Science 319:1260–1264

    Article  CAS  PubMed  Google Scholar 

  • Nicholls RE, Alarcon JM, Malleret G, Carroll RC, Grody M et al (2008) Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility. Neuron 58:104–117

    Article  CAS  PubMed  Google Scholar 

  • Ohishi H, Akazawa C, Shigemoto R, Nakanishi S, Mizuno N (1995) Distributions of the mRNAs for L-2-amino-4-phosphonobutyrate-sensitive metabotropic glutamate receptors, mGluR4 and mGluR7, in the rat brain. J Comp Neurol 360:555–570

    Article  CAS  PubMed  Google Scholar 

  • Pelkey KA, Askalan R, Paul S, Kalia LV, Nguyen TH et al (2002) Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation. Neuron 34:127–138

    Article  CAS  PubMed  Google Scholar 

  • Rabinovich Orlandi I, Fullio CL, Schroeder MN, Giurfa M, Ballarini F, Moncada D (2020) Behavioral tagging underlies memory reconsolidation. Proc Natl Acad Sci USA 117:18029–18036

    Article  PubMed  PubMed Central  Google Scholar 

  • Redondo RL, Morris RG (2011) Making memories last: the synaptic tagging and capture hypothesis. Nat Rev Neurosci 12:17–30

    Article  CAS  PubMed  Google Scholar 

  • Robert V, Therreau L, Chevaleyre V, Lepicard E, Viollet C et al (2021) Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1. elife 10

    Google Scholar 

  • Sah P, Faber ES, Lopez De Armentia M, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83:803–834

    Article  CAS  PubMed  Google Scholar 

  • Sajikumar S, Frey JU (2004) Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD. Neurobiol Learn Mem 82:12–25

    Article  CAS  PubMed  Google Scholar 

  • Sajikumar S, Morris RG, Korte M (2014) Competition between recently potentiated synaptic inputs reveals a winner-take-all phase of synaptic tagging and capture. Proc Natl Acad Sci USA 111:12217–12221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sajikumar S, Navakkode S, Sacktor TC, Frey JU (2005) Synaptic tagging and cross-tagging: the role of protein kinase Mzeta in maintaining long-term potentiation but not long-term depression. J Neurosci 25:5750–5756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shetty MS, Sharma M, Hui NS, Dasgupta A, Gopinadhan S, Sajikumar S (2015) Investigation of synaptic tagging/capture and cross-capture using acute hippocampal slices from rodents. J Vis Exp 103:e53008

    Google Scholar 

  • Skrede KK, Westgaard RH (1971) The transverse hippocampal slice: a well-defined cortical structure maintained in vitro. Brain Res 35:589–593

    Article  CAS  PubMed  Google Scholar 

  • Sossin WS (2018) Memory synapses are defined by distinct molecular complexes: a proposal. Front Synaptic Neurosci 10:5

    Article  PubMed  PubMed Central  Google Scholar 

  • Squire LR (1992) Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 99:195–231

    Article  CAS  PubMed  Google Scholar 

  • Squire LR, Genzel L, Wixted JT, Morris RG (2015) Memory consolidation. Cold Spring Harb Perspect Biol 7:a021766

    Article  PubMed  PubMed Central  Google Scholar 

  • Tse D, Langston RF, Kakeyama M, Bethus I, Spooner PA et al (2007) Schemas and memory consolidation. Science 316:76–82

    Article  CAS  PubMed  Google Scholar 

  • Vago DR, Kesner RP (2008) Disruption of the direct perforant path input to the CA1 subregion of the dorsal hippocampus interferes with spatial working memory and novelty detection. Behav Brain Res 189:273–283

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhao M, Choi YS, Obrietan K, Dudek SM (2007) Synaptic plasticity (and the lack thereof) in hippocampal CA2 neurons. J Neurosci 27:12025–12032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Mohammad Zaki Bin Ibrahim & Sreedharan Sajikumar

Authors
  1. Mohammad Zaki Bin Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sreedharan Sajikumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sreedharan Sajikumar .

Editor information

Editors and Affiliations

  1. Physiology and Health Longevity, National University of Singapore, Kent Ridge, Singapore

    Sreedharan Sajikumar

  2. Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA

    Ted Abel

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bin Ibrahim, M.Z., Sajikumar, S. (2024). Exploring New Horizons: Synaptic Tagging and Capture Beyond Space and Time. In: Sajikumar, S., Abel, T. (eds) Synaptic Tagging and Capture. Springer, Cham. https://doi.org/10.1007/978-3-031-54864-2_12

Download citation

Publish with us

Policies and ethics

Search

Navigation