Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity

Simón(e) D. Sun, Daniel Levenstein, Boxing Li, Nataniel Mandelberg, Nicolas Chenouard, Benjamin S. Suutari, Sandrine Sanchez, Guoling Tian, John Rinzel, György Buzsáki, Richard W. Tsien

Research output: Contribution to journalArticlepeer-review


Homeostatic regulation of synapses is vital for nervous system function and key to understanding a range of neurological conditions. Synaptic homeostasis is proposed to operate over hours to counteract the destabilizing influence of long-term potentiation (LTP) and long-term depression (LTD). The prevailing view holds that synaptic scaling is a slow first-order process that regulates postsynaptic glutamate receptors and fundamentally differs from LTP or LTD. Surprisingly, we find that the dynamics of scaling induced by neuronal inactivity are not exponential or monotonic, and the mechanism requires calcineurin and CaMKII, molecules dominant in LTD and LTP. Our quantitative model of these enzymes reconstructs the unexpected dynamics of homeostatic scaling and reveals how synapses can efficiently safeguard future capacity for synaptic plasticity. This mechanism of synaptic adaptation supports a broader set of homeostatic changes, including action potential autoregulation, and invites further inquiry into how such a mechanism varies in health and disease.

Original languageEnglish (US)
Article number113839
JournalCell Reports
Issue number4
StatePublished - Apr 23 2024


  • CP: Neuroscience
  • CaMKII
  • Hebbian plasticity
  • calcineurin
  • homeostasis
  • inactivity
  • long-term depression
  • long-term potentiation
  • oscillation
  • synapse
  • synaptic scaling

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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