Linking functional and structural dendritic spine remodeling during fear learning and extinction in vivo.

Structural plasticity of dendritic spines has been observed during different learning paradigms, but how the functional dynamics of dendritic spines changes with memory processing and how these patterns relate to structural plasticity and dendritic integration remain unclear. Here, we perform longitudinal functional and structural in vivo imaging of the frontal association cortex in mice subject to fear conditioning and extinction over several days. We show that fear learning induced responsive spines that are more likely to be synchronous and clustered, which are consolidated over the following days but attenuated by extinction. We develop a causal inference model demonstrating that the active spine calcium signals during fear learning prevent the spines from being eliminated while promoting the elimination of neighboring spines after memory consolidation. Furthermore, the dendritic responsive signal reveals a learning-dependent tone discrimination pattern that is correlated to spines' structural remodeling. Our findings provide in vivo evidence consistent with functional-structural link of dendritic spines in a bidirectional learning paradigm.