Distinct Neuronal Populations Contribute to Trace Conditioning and Extinction Learning in the Hippocampal CA1

Trace conditioning and extinction learning depend on the hippocampus, but it remains unclear how ongoing neural activities in the hippocampus are modulated during different learning processes. To explore this question, we performed calcium imaging in a large number of individual CA1 neurons during both trace eye-blink conditioning and subsequent extinction learning in mice. Using trial-averaged calcium fluorescence analysis, we found direct evidence that in real time, as learning emerges, distinct populations of CA1 cells contribute to trace conditioned learning versus extinction learning. Furthermore, we examined network connectivity by calculating co-activity between CA1 neuron pairs, and found that CA1 network connectivity is different between conditioning and extinction and between correct versus incorrect behavioral responses during trace conditioned learning. However, the overall connectivity density remains constant across these behavioral conditions. Together, our results demonstrate that distinct populations of CA1 neurons, forming different sub-networks with unique connectivity patterns, encode different aspects of learning.