Homeostatic plasticity scales dendritic spine volumes and changes the threshold and specificity of Hebbian plasticity

Abstract

Information is encoded within neural networks through synaptic weight changes. Synaptic learning rules involve a combination of rapid Hebbian plasticity with slower homeostatic synaptic plasticity (HSP) that regulates neuronal activity through global synaptic scaling. While Hebbian plasticity has been extensively investigated, much less is known about HSP. Here we investigate the structural and functional consequences of HSP at dendritic spines of mouse hippocampal neurons. We find that prolonged activity blockade induces spine growth, paralleling synaptic strength increases. Following activity blockade, glutamate uncaging-mediated long-term potentiation at single spines leads to size-dependent structural plasticity: smaller spines undergo robust growth, while larger spines remain unchanged. Moreover, we find that neighboring spines in the vicinity of the stimulated spine exhibit volume changes following HSP, indicating that plasticity has spread across a group of synapses. Overall, these findings demonstrate that Hebbian and homeostatic plasticity shape neural connectivity through coordinated structural plasticity of clustered inputs.