Heterosynaptic Structural Plasticity on Local Dendritic Segments of Hippocampal CA1 Neurons

Competition between synapses contributes to activity-dependent refinement of the nervous system during development. Does local competition between neighboring synapses drive circuit remodeling during experience-dependent plasticity in the cerebral cortex? Here, we examined the role of activity-mediated competitive interactions in regulating dendritic spine structure and function on hippocampal CA1 neurons. We found that high-frequency glutamatergic stimulation at individual spines, which leads to input-specific synaptic potentiation, induces shrinkage and weakening of nearby unstimulated synapses. This heterosynaptic plasticity requires potentiation of multiple neighboring spines, suggesting that a local threshold of neural activity exists beyond which inactive synapses are punished. Notably, inhibition of calcineurin, IP3Rs, or group I metabotropic glutamate receptors (mGluRs) blocked heterosynaptic shrinkage without blocking structural potentiation, and inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) blocked structural potentiation without blocking heterosynaptic shrinkage. Our results support a model in which activity-induced shrinkage signal, and not competition for limited structural resources, drives heterosynaptic structural and functional depression during neural circuit refinement. [Display omitted] •Local competition between hippocampal synapses drives synaptic structural changes•Structural potentiation of multiple spines drives shrinkage of nearby inactive spines•Heterosynaptic spine shrinkage is tightly coupled to synaptic weakening•Heterosynaptic spine shrinkage requires activation of calcineurin, IP3Rs, and mGluRs Plasticity of neuronal structure, such as the growth and retraction of dendritic spines, is thought to support neural circuit remodeling early in development and during learning in the adult. Oh et al. identify a novel role for competitive interactions between neighboring synapses in driving structural and functional changes in excitatory synapses on dendritic spines in the cerebral cortex.