Skip to main content
SpringerLink
Log in

Multiple spine boutons are formed after long-lasting LTP in the awake rat

  • Short Communication
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

The formation of multiple spine boutons (MSBs) has been associated with cognitive abilities including hippocampal-dependent associative learning and memory. Data obtained from cultured hippocampal slices suggest that the long-term maintenance of synaptic plasticity requires the formation of new synaptic contacts on pre-existing synapses. This postulate however, has never been tested in the awake, freely moving animals. In the current study, we induced long-term potentiation (LTP) in the dentate gyrus (DG) of awake adult rats and performed 3-D reconstructions of electron micrographs from thin sections of both axonal boutons and dendritic spines, 24 h post-induction. The specificity of the observed changes was demonstrated by comparison with animals in which long-term depression (LTD) had been induced, or with animals in which LTP was blocked by an N-methyl-d-aspartate (NMDA) antagonist. Our data demonstrate that whilst the number of boutons remains unchanged, there is a marked increase in the number of synapses per bouton 24 h after the induction of LTP. Further, we demonstrate that this increase is specific to mushroom spines and not attributable to their division. The present investigation thus fills the gap existing between behavioural and in vitro studies on the role of MSB formation in synaptic plasticity and cognitive abilities.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Abbreviations

CPP:

3-[(R)-2-Carboxypiperazin-4-yl]-propyl-1-phosphonic acid

DG:

Dentate gyrus

EPSP:

Excitatory postsynaptic potential

HFS:

High-frequency stimulation

LPP:

Lateral perforant path

LTD:

Long-term depression

LTP:

Long-term potentiation

MML:

Middle of the molecular layer (of dentate gyrus)

MPP:

Medial perforant path

NMDA:

N-methyl-d-aspartate

PSD:

Post-synaptic density

PSDs:

Postsynaptic densities

References

  • Abraham WC (2003) How long will long-term potentiation last? Phil Trans R Soc London Ser B Biol Sci 358:735–744

    Article  Google Scholar 

  • Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  CAS  PubMed  Google Scholar 

  • Bourne J, Harris KM (2007) Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol 17:381–386

    Article  CAS  PubMed  Google Scholar 

  • Bourne JN, Harris KM (2008) Balancing structure and function at hippocampal dendritic spines. Ann Rev Neurosci 31:47–67

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Carlin RK, Siekevitz P (1983) Plasticity in the central nervous system: do synapses divide? Proc Natl Acad Sci USA 80:3517–3521

    Article  CAS  PubMed  Google Scholar 

  • Caroni P, Donato F, Muller D (2012) Structural plasticity upon learning: regulation and functions. Nat Rev Neurosci 13:478–490

    Article  CAS  PubMed  Google Scholar 

  • De Roo M, Klauser P, Muller D (2008) LTP promotes a selective long-term stabilization and clustering of dendritic spines. PLoS Biol 6:e219

    Article  PubMed Central  PubMed  Google Scholar 

  • Doyère V, Laroche S (1992) Linear relationship between the maintenance of hippocampal long-term potentiation and retention of an associative memory. Hippocampus 2:39–48

    Article  PubMed  Google Scholar 

  • Doyere V, Srebro B, Laroche S, Doyère V (1997) Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat. J Neurophysiol 77:571–578

    CAS  PubMed  Google Scholar 

  • Federmeier KD, Kleim JA, Greenough WT (2002) Learning-induced multiple synapse formation in rat cerebellar cortex. Neurosci Lett 332:180–184

    Article  CAS  PubMed  Google Scholar 

  • Fiala JC, Harris KM (2001) Extending unbiased stereology of brain ultrastructure to three-dimensional volumes. J Am Med Inform Assoc JAMIA 8(1):1–16

    Article  CAS  Google Scholar 

  • Fiala JC, Allwardt B, Harris KM (2002) Dendritic spines do not split during hippocampal LTP or maturation. Nature Neurosci 5:297–298

    Article  CAS  PubMed  Google Scholar 

  • Geinisman Y, Berry RW, Disterhoft JF, Power JM, Van der Zee EA (2001) Associative learning elicits the formation of multiple-synapse boutons. J Neurosci 21:5568–5573

    CAS  PubMed  Google Scholar 

  • Grutzendler J, Kasthuri N, Gan W-B (2002) Long-term dendritic spine stability in the adult cortex. Nature 420:812–816

    Article  CAS  PubMed  Google Scholar 

  • Halpain S (2000) Actin and the agile spine: how and why do dendritic spines dance? Trends Neurosci 23:141–146

    Article  CAS  PubMed  Google Scholar 

  • Harris KM (1995) How multiple-synapse boutons could preserve input specificity during an interneuronal spread of LTP. Trends Neurosci 18:365–369

    Article  CAS  PubMed  Google Scholar 

  • Harris KM, Jensen FE, Tsao B (1992) Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long term potentiation. J Neurosci 12:2685–2705

    CAS  PubMed  Google Scholar 

  • Holtmaat AJ, Trachtenberg JT, Wilbrecht L, Shepherd GM, Zhang X, Knott GW, Svoboda K (2005) Transient and persistent dendritic spines in the neocortex in vivo. Neuron 45(2):279–291

    Article  CAS  PubMed  Google Scholar 

  • Holtmaat A, Wilbrecht L, Knott GW, Welker E, Svoboda K (2006) Experience-dependent and cell-type-specific spine growth in the neocortex. Nature 441:979–983

    Article  CAS  PubMed  Google Scholar 

  • Holtmaat A, De Paola V, Wilbrecht L, Knott GW (2008) Imaging of experience-dependent structural plasticity in the mouse neocortex in vivo. Behav Brain Res 192:20–25

    Article  CAS  PubMed  Google Scholar 

  • Jones TA (1999) Multiple synapse formation in the motor cortex opposite unilateral sensorimotor cortex lesions in adult rats. J Comp Neurol 414:57–66

    Article  CAS  PubMed  Google Scholar 

  • Jones TA, Klintsova AY, Kilman VL, Sirevaag AM, Greenough WT (1997) Induction of multiple synapses by experience in the visual cortex of adult rats. Neurobiol Learn Mem 68:13–20

    Google Scholar 

  • Lüscher C, Nicoll RA, Malenka RC, Muller D, Luscher C (2000) Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nat Neurosci 3:545–550

    Article  PubMed  Google Scholar 

  • Mackenzie PJ, Kenner GS, Prange O, Shayan H, Umemiya M et al (1999) Ultrastructural correlates of quantal synaptic function at single CNS synapses. J Neurosci 19(12):RC13

    Google Scholar 

  • Medvedev NI, Popov VI, Arellano JJR, Dallérac G, Davies HA et al (2010a) The N-methyl-d-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat. Neurosci 165(4):1170–1181

    Article  CAS  Google Scholar 

  • Medvedev NI, Popov VI, Dallérac G, Davies HA, Laroche S et al (2010b) Alterations in synaptic curvature in the dentate gyrus following induction of long-term potentiation, long-term depression, and treatment with the N-methyl-d-aspartate receptor antagonist CPP. Neurosci 171:390–397

    Article  CAS  Google Scholar 

  • Nicholson D, Geinisman Y (2009) Axospinous synaptic subtype-specific differences in structure, size, ionotropic receptor expression, and connectivity in apical dendritic regions of rat hippocampal CA1 pyramidal neurons. J Comp Neurol 512(3):399–418

    Article  PubMed Central  PubMed  Google Scholar 

  • Park M, Salgado JM, Ostroff L, Helton TD, Robinson CG et al (2006) Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes. Neuron 52:817–830

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Peters A, Kaiserman-Abramof IR (1970) The small pyramidal neuron of the rat cerebral cortex: the perikaryon, dendrites and spines. Am J Anat 127:321–356

    Article  CAS  PubMed  Google Scholar 

  • Pierce JP, Lewin GR (1994) An ultrastructural size principle. Neuroscience 58:441–446

    Article  CAS  PubMed  Google Scholar 

  • Popov VI, Davies HA, Rogachevsky VV, Patrushev IV, Errington ML et al (2004) Remodelling of synaptic morphology but unchanged synaptic density during late phase long-term potentiation (LTP): a serial section electron micrograph study in the dentate gyrus in the anaesthetised rat. Neurosci 128:251–262

    Article  CAS  Google Scholar 

  • Popov V, Medvedev NI, Davies HA, Stewart MG (2005) Mitochondria form a filamentous reticular network in hippocampal dendrites but are present as discrete bodies in axons: a three-dimensional ultrastructural study. J Comp Neurol 492:50–65

    Article  PubMed  Google Scholar 

  • Popov VI, Medvedev NI, Kraev IV, Gabbott PL, Davies HA et al (2008) A cell adhesion molecule mimetic, FGL peptide, induces alterations in synapse and dendritic spine structure in the dentate gyrus of aged rats: a three-dimensional ultrastructural study. Eur J Neurosci 27:301–314

    Article  PubMed  Google Scholar 

  • Reilly JE, Hanson HH, Fernández-Monreal M, Wearne SL, Hof PR, Phillips GR (2011) Characterization of MSB synapses in dissociated hippocampal culture with simultaneous pre- and postsynaptic live microscopy. PloS One 6(10):e26478. (Epub 2011)

    Google Scholar 

  • Staubli U, Lynch G (1987) Stable hippocampal long-term potentiation elicited by “theta” pattern stimulation. Brain Res 435:227–234

    Article  CAS  PubMed  Google Scholar 

  • Stewart MG, Medvedev NI, Popov VI, Schoepfer R, Davies HA et al (2005) Chemically induced long-term potentiation increases the number of perforated and complex postsynaptic densities but does not alter dendritic spine volume in CA1 of adult mouse hippocampal slices. Eur J Neurosci 21:3368–3378

    Article  CAS  PubMed  Google Scholar 

  • Toni N, Buchs PA, Nikonenko I, Bron CR, Muller D (1999) LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402:421–425

    Article  CAS  PubMed  Google Scholar 

  • Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR et al (2002) Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420:788–794

    Article  CAS  PubMed  Google Scholar 

  • Yeow MB, Peterson EH (1991) Active zone organization and vesicle content scale with bouton size at a vertebrate central synapse. J Comp Neurol 307:475–486

    Article  CAS  PubMed  Google Scholar 

  • Yuste R, Bonhoeffer T (2001) Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 24:1071–1089

    Article  CAS  PubMed  Google Scholar 

  • Zuo Y, Yang G, Kwon E, Gan W-B (2005) Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436:261–265

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by EU FPVI Promemoria Contract No. 512012 and BBSRC grant No BB/1020330/1.

Author information

Author notes

  1. N. I. Medvedev

    Present address: ZIK HIKE, University of Greifswald, 17489, Greifswald, Germany

  2. G. Dallérac

    Present address: Faculte de Medecine secteur Nord, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille UMR6231-CNRS-Universite Aix-Marseille II et III, 13344, Marseille Cedex 15, France

Authors and Affiliations

  1. Department of Life Sciences, The Open University, Walton Hall, Milton Keynes, MK7 6AA, UK

    N. I. Medvedev, V. I. Popov, J. J. Rodriguez Arellano, H. A. Davies, I. V. Kraev & M. G. Stewart

  2. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, RF, Russia

    V. I. Popov

  3. UMR 8195, Centre de Neurosciences Paris-Sud, Univ Paris-Sud, 91405, Orsay, France

    G. Dallérac & V. Doyère

  4. CNRS, 91405, Orsay, France

    G. Dallérac & V. Doyère

  5. IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    J. J. Rodriguez Arellano

  6. Department of Neurosciences, University of the Basque Country UPVEHU, 48940, Leioa, Spain

    J. J. Rodriguez Arellano

Authors
  1. N. I. Medvedev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Dallérac
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. I. Popov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. J. Rodriguez Arellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. A. Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I. V. Kraev
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. Doyère
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. G. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. G. Stewart.

Additional information

N. I. Medvedev, G. Dallérac contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Medvedev, N.I., Dallérac, G., Popov, V.I. et al. Multiple spine boutons are formed after long-lasting LTP in the awake rat. Brain Struct Funct 219, 407–414 (2014). https://doi.org/10.1007/s00429-012-0488-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-012-0488-0

Keywords

Search

Navigation