Long-Term Consolidation of Ensemble Neural Plasticity Patterns in Hippocampal Area CA1

Neural network remodeling underpins the ability to remember life experiences, but little is known about the long-term plasticity of neural populations. To study how the brain encodes episodic events, we used time-lapse two-photon microscopy and a fluorescent reporter of neural plasticity based on an enhanced form of the synaptic activity-responsive element (E-SARE) within the Arc promoter to track thousands of CA1 hippocampal pyramidal cells over weeks in mice that repeatedly encountered different environments. Each environment evokes characteristic patterns of ensemble neural plasticity, but with each encounter, the set of activated cells gradually evolves. After repeated exposures, the plasticity patterns evoked by an individual environment progressively stabilize. Compared with young adults, plasticity patterns in aged mice are less specific to individual environments and less stable across repeat experiences. Long-term consolidation of hippocampal plasticity patterns may support long-term memory formation, whereas weaker consolidation in aged subjects might reflect declining memory function. [Display omitted] •Long-term imaging of hippocampal neural ensemble plasticity patterns in live mice•Plasticity patterns in hippocampal area CA1 encode specific behavioral episodes•Over repeat episodes, CA1 plasticity patterns turn over but progressively stabilize•Aging degrades the stability and specificity of plasticity patterns Attardo et al. use a fluorescent reporter of neural plasticity to image ensemble plasticity patterns in hippocampal neurons of live mice. These patterns turn over but progressively stabilize across repeated explorations of an enriched environment. In aged mice, plasticity patterns do not stabilize and are less specific to individual environments.