Learning-prolonged maintenance of stimulus information in CA1 and subiculum during trace fear conditioning

Temporal associative learning binds discontiguous conditional stimuli (CSs) and unconditional stimuli (USs), possibly by maintaining CS information in the hippocampus after its offset. Yet, how learning regulates such maintenance of CS information in hippocampal circuits remains largely unclear. Using the auditory trace fear conditioning (TFC) paradigm, we identify a projection from the CA1 to the subiculum critical for TFC. Deep-brain calcium imaging shows that the peak of trace activity in the CA1 and subiculum is extended toward the US and that the CS representation during the trace period is enhanced during learning. Interestingly, such plasticity is consolidated only in the CA1, not the subiculum, after training. Moreover, CA1 neurons, but not subiculum neurons, increasingly become active during CS-and-trace and shock periods, respectively, and correlate with CS-evoked fear retrieval afterward. These results indicate that learning dynamically enhances stimulus information maintenance in the CA1-subiculum circuit during learning while storing CS and US memories primarily in the CA1 area. [Display omitted] •Both CA1 and subiculum maintain stimulus information in the post-stimulus trace periods•The CA1-to-subiculum projection is critical for temporal associative learning•Continuous learning promotes a better and longer maintenance of stimulus information•Learning-induced plasticity is primarily consolidated in CA1 but not subiculum Using miniscope Ca2+ imaging and optogenetics in behaving mice, Bai et al. demonstrate a learning-induced plasticity of stimulus information maintenance in the CA1 and subiculum. Such plasticity results in enhanced and prolonged maintenance of stimulus information and is critical for the formation of temporal associative memory.