A role for hippocampal CA1 in structural learning in mice

Learning relationships between cues in our environment enables us to recognise common underlying structures of events and is thought to form the basis of episodic memory. This type of learning - often called relational or structural learning - requires retaining the identity of a stimulus as well as its relation to other cues, for example its position in time or location in space. One area implicated in structural learning is the hippocampus. Specifically, neurons in the CA1 area of the hippocampus have been shown to represent variables essential for constructing a relational structure of the environment, such as cue configurations and their order in space and time. To investigate the neural mechanisms of structural learning, we designed an odour-based task that requires mice to learn not only about sets of odour cues, but about their relative order in time. Importantly, the task design allows for manipulation of the temporal structure and identity of cues separately, allowing dissociation of their neural mechanisms. Using this task, we found that mice can generalise learnt structures across large changes in both timing and identity of cues, suggesting flexible use of previously learnt relational structures. In line with a role for hippocampal circuitry, optogenetic inactivation of ventral CA1 (vCA1) markedly impaired task performance, but only when cues were separated across a delay longer than 10s. Together we show that mice can rapidly learn and flexibly perform an olfactory structural learning task, and that vCA1 plays an important role in connecting the individual cues of the structure across a delay. Using single-cell calcium imaging, our ongoing work is investigating how neurons in vCA1 represent unique features in this task, in particular the means by which odour information is maintained across the delay period. Together, the project aims to understand how vCA1 contributes to structural learning and its generalisation.