Time course of homeostatic structural plasticity in response to optogenetic stimulation in mouse anterior cingulate cortex

Plasticity is the mechanistic basis of development, aging, learning and memory, both in healthy and pathological brains. Structural plasticity is rarely accounted for in computational network models, due to a lack of insight into the underlying neuronal mechanisms and processes. Little is known about how the rewiring of networks is dynamically regulated. To inform such models, we characterized the time course of neural activity, the expression of synaptic proteins, and neural morphology employing an in vivo optogenetic mouse model. We stimulated pyramidal neurons in the anterior cingulate cortex of mice and harvested their brains at 1.5 h, 24 h, and 48 h after stimulation. Stimulus-induced cortical hyperactivity persisted up to 1.5 h and decayed to baseline after 24 h, indicated by c-Fos expression. The synaptic proteins VGLUT1 and PSD-95, in contrast, were upregulated at 24 h and downregulated at 48 h, respectively. Spine density and spine head volume were also increased at 24 h and decreased at 48 h. This specific sequence of events reflects a continuous joint evolution of activity and connectivity that is characteristic of the model of homeostatic structural plasticity. Our computer simulations thus corroborate the observed empirical evidence from our animal experiments.