RT Journal Article
SR Electronic
T1 Synaptic homeostasis transiently leverages Hebbian mechanisms for a multiphasic response to inactivity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.18.496642
DO 10.1101/2022.06.18.496642
A1 Simón(e) D. Sun
A1 Daniel Levenstein
A1 Boxing Li
A1 Nataniel Mandelberg
A1 Nicolas Chenouard
A1 Benjamin S. Suutari
A1 Sandrine Sanchez
A1 Guoling Tian
A1 John Rinzel
A1 György Buzsáki
A1 Richard W. Tsien
YR 2022
UL http://biorxiv.org/content/early/2022/06/21/2022.06.18.496642.abstract
AB Neurons use various forms of negative feedback to maintain their synaptic strengths within an operationally useful range. While this homeostatic plasticity is thought to distinctly counteract the destabilizing positive feedback of Hebbian plasticity, there is considerable overlap in the molecular components mediating both forms of plasticity. The varying kinetics of these components spurs additional inquiry into the dynamics of synaptic homeostasis. We discovered that upscaling of synaptic weights in response to prolonged inactivity is nonmonotonic. Surprisingly, this seemingly oscillatory adaptation involved transient appropriation of molecular effectors associated with Hebbian plasticity, namely CaMKII, L-type Ca2+ channels, and Ca2+-permeable AMPARs, and homeostatic elements such as calcineurin. We created a dynamic model that shows how traditionally “Hebbian” and “homeostatic” mechanisms can cooperate to autoregulate postsynaptic Ca2+ levels. We propose that this combination of mechanisms allows excitatory synapses to adapt to prolonged activity changes and safeguard the capability to undergo future strengthening on demand.Competing Interest StatementThe authors have declared no competing interest.