Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors

Jason D. Shepherd, Gavin Rumbaugh, Jing Wu, Shoaib Chowdhury, Niels Plath, Dietmar Kuhl, Richard L Huganir, Paul F Worley

Research output: Contribution to journalArticle

Abstract

Homeostatic plasticity may compensate for Hebbian forms of synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD), by scaling neuronal output without changing the relative strength of individual synapses. This delicate balance between neuronal output and distributed synaptic weight may be necessary for maintaining efficient encoding of information across neuronal networks. Here, we demonstrate that Arc/Arg3.1, an immediate-early gene (IEG) that is rapidly induced by neuronal activity associated with information encoding in the brain, mediates homeostatic synaptic scaling of AMPA type glutamate receptors (AMPARs) via its ability to activate a novel and selective AMPAR endocytic pathway. High levels of Arc/Arg3.1 block the homeostatic increases in AMPAR function induced by chronic neuronal inactivity. Conversely, loss of Arc/Arg3.1 results in increased AMPAR function and abolishes homeostatic scaling of AMPARs. These observations, together with evidence that Arc/Arg3.1 is required for memory consolidation, reveal the importance of Arc/Arg3.1's dynamic expression as it exerts continuous and precise control over synaptic strength and cellular excitability.

Original languageEnglish (US)
Pages (from-to)475-484
Number of pages10
JournalNeuron
Volume52
Issue number3
DOIs
StatePublished - Nov 9 2006

Fingerprint

AMPA Receptors
Glutamate Receptors
Neuronal Plasticity
Immediate-Early Genes
Aptitude
Long-Term Potentiation
Synapses
Depression
Weights and Measures
Brain

Keywords

  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Shepherd, J. D., Rumbaugh, G., Wu, J., Chowdhury, S., Plath, N., Kuhl, D., ... Worley, P. F. (2006). Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors. Neuron, 52(3), 475-484. https://doi.org/10.1016/j.neuron.2006.08.034

Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors. / Shepherd, Jason D.; Rumbaugh, Gavin; Wu, Jing; Chowdhury, Shoaib; Plath, Niels; Kuhl, Dietmar; Huganir, Richard L; Worley, Paul F.

In: Neuron, Vol. 52, No. 3, 09.11.2006, p. 475-484.

Research output: Contribution to journalArticle

Shepherd, JD, Rumbaugh, G, Wu, J, Chowdhury, S, Plath, N, Kuhl, D, Huganir, RL & Worley, PF 2006, 'Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors', Neuron, vol. 52, no. 3, pp. 475-484. https://doi.org/10.1016/j.neuron.2006.08.034
Shepherd JD, Rumbaugh G, Wu J, Chowdhury S, Plath N, Kuhl D et al. Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors. Neuron. 2006 Nov 9;52(3):475-484. https://doi.org/10.1016/j.neuron.2006.08.034
Shepherd, Jason D. ; Rumbaugh, Gavin ; Wu, Jing ; Chowdhury, Shoaib ; Plath, Niels ; Kuhl, Dietmar ; Huganir, Richard L ; Worley, Paul F. / Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors. In: Neuron. 2006 ; Vol. 52, No. 3. pp. 475-484.
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