Trends in Neurosciences
Volume 27, Issue 12, December 2004, Pages 744-750
Journal home page for Trends in Neurosciences

Discrete synaptic states define a major mechanism of synapse plasticity

https://doi.org/10.1016/j.tins.2004.10.006Get rights and content

Synapses can change their strength in response to afferent activity, a property that might underlie a variety of neural processes such as learning, network synaptic weighting, synapse formation and pruning. Recent work has shown that synapses change their strength by jumping between discrete mechanistic states, rather than by simply moving up and down in a continuum of efficacy. Coincident with this, studies have provided a framework for understanding the potential mechanistic underpinnings of synaptic plastic states. Synaptic plasticity states not only represent a new and fundamental property of CNS synapses, but also can provide a context for understanding outstanding issues in synaptic function, plasticity and development.

Section snippets

Synaptic states: a mechanism of dictating synaptic strength

A key role of synaptic plasticity is to allow the synapse to operate over a large dynamic range. Two possible models could explain the behavior of synapses over this range. In the first, synapses undergo changes in efficacy by adjusting their strength along a continuum, such that the properties of strengthening or weakening occur in a graded fashion with fixed underlying mechanisms (i.e. the ‘continuum model’). In the second, synapses might exist in different discrete states that represent and

Why have discrete plastic states?

Synaptic plasticity that occurs in a state-dependent manner increases the information-carrying capacity of a synapse, in that the potentiation or depression of a synapse has an historical aspect that is absent from a simple continuum model. In a continuum model, information is coded solely in the current strength of the synapse, whereas a state model adds to the coded information the history of the synapse, because the ability of a synapse to undergo, and mechanisms for undergoing, further

Future questions: what molecular changes could define synaptic states?

Clearly, synapses can undergo plastic changes by switching between different states, but what cellular mechanisms underlie these states? Currently, each state is defined physiologically by AMPA receptor retrieval from the membrane, and/or the triggering of this retrieval. It is important to appreciate that AMPA receptor regulation is probably not the sole property defining a given state. Many other known presynaptic or postsynaptic processes could play a role in the definition of plastic states

Concluding remarks

That synapses exist in several discrete plasticity states represents a new paradigm for understanding the mechanistic underpinnings of synaptic plasticity, and perhaps also the roles of such plasticity in higher brain functions. Much work remains to be done to define and understand the mechanisms and roles these states play. Emerging data are beginning to elucidate how synaptic plasticity states could arise. Although these states will probably not be specified by a single simple mechanism, it

Acknowledgements

We would like to acknowledge Craig Garner for his insightful comments, and also members of the Madison Laboratory for reading the manuscript and providing their input.

References (59)

  • J.M. Montgomery et al.

    State-dependent heterogeneity in synaptic depression between pyramidal cell pairs

    Neuron

    (2002)
  • S.M. Fitzjohn

    The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity

    Neuropharmacology

    (1998)
  • D.M. Kullmann

    Amplitude fluctuations of dual-component EPSCs in hippocampal pyramidal cells: implications for long-term potentiation

    Neuron

    (1994)
  • S.N. Gomperts

    Postsynaptically silent synapses in single neuron cultures

    Neuron

    (1998)
  • J.T. Isaac

    Silent synapses during development of thalamocortical inputs

    Neuron

    (1997)
  • Y. Meng

    Synaptic transmission and plasticity in the absence of AMPA glutamate receptor GluR2 and GluR3

    Neuron

    (2003)
  • M.D. Ehlers

    Reinsertion or degradation of AMPA receptors determined by activity-dependent endocytic sorting

    Neuron

    (2000)
  • H.K. Lee

    Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory

    Cell

    (2003)
  • H.C. Kornau

    Interaction of ion channels and receptors with PDZ domain proteins

    Curr. Opin. Neurobiol.

    (1997)
  • C.C. Garner

    PDZ domains in synapse assembly and signalling

    Trends Cell Biol.

    (2000)
  • J. Xia

    Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1

    Neuron

    (1999)
  • M. Colledge

    Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression

    Neuron

    (2003)
  • W.C. Abraham et al.

    Metaplasticity: the plasticity of synaptic plasticity

    Trends Neurosci.

    (1996)
  • T.V. Bliss et al.

    A synaptic model of memory: long-term potentiation in the hippocampus

    Nature

    (1993)
  • R. Malinow et al.

    AMPA receptor trafficking and synaptic plasticity

    Annu. Rev. Neurosci.

    (2002)
  • T.V. Bliss et al.

    Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path

    J. Physiol.

    (1973)
  • S.M. Dudek et al.

    Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade

    Proc. Natl. Acad. Sci. U. S. A.

    (1992)
  • T.A. Benke

    Collingridge. Modulation of AMPA receptor unitary conductance by synaptic activity

    Nature

    (1998)
  • M.G. Weisskopf et al.

    Presynaptic changes during mossy fibre LTP revealed by NMDA receptor-mediated synaptic responses

    Nature

    (1995)
  • Cited by (0)

    View full text