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
Affiliations
Simón(e) D. Sun
Center for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
Daniel Levenstein
Center for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, 3810 University Street, Montreal, QC, Canada
Boxing Li
Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Neuroscience Program, Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine and the Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510810, China
Nataniel Mandelberg
Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA
Nicolas Chenouard
Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Sorbonne Université, INSERM U1127, UMR CNRS 7225, Institut du Cerveau (ICM), 47 bld de l’hôpital, 75013 Paris, France
Benjamin S. Suutari
Center for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA
Sandrine Sanchez
Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA
Guoling Tian
Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA
John Rinzel
Center for Neural Science, New York University, New York, NY 10003, USA
György Buzsáki
Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA
Richard W. Tsien
Center for Neural Science, New York University, New York, NY 10003, USA; Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA; Corresponding author
Summary: 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.
