Investigating the role of the hippocampus in learning temporal structure

The hippocampus plays a key role in spatial navigation and representation of space as well as in relational memory (O'Keefe and Nadel, 1978; Eichenbaum, 2000). It has recently been suggested that hippocampal involvement in these different functions may reflect a fundamental role of the hippocampus in creating a cognitive map that represents the relational structure of sensory input (Aggleton et al. 2007; Whittington et al. 2020; Rudy and Sutherland, 1989) as well as more abstract variables such as task structure (Zhou et al. 2019). However, how the hippocampal circuit performs this more general role is unknown.

In addition, the function of the hippocampus is thought to be distinct along the dorsal:ventral axis, where dorsal hippocampus encodes fine structure across short time periods, and is most utilized during later, more refined stages of learning. In contrast, ventral hippocampus is thought to encode structure over longer time periods, to integrate this information with salience and affective information, and is utilized at early stages of learning, or during periods of uncertainty. Therefore, a key but untested hypothesis is that the role of the hippocampus in learning about relational structure may differ across the dorsal:ventral axis.

To investigate this, I have developed a novel task that requires mice to learn the order, or temporal structure, of pairs of distinct odour stimuli separated in time. I will use this task to investigate the neural mechanisms underlying the learning and performance of this task. I will first compare the role of dorsal and ventral hippocampal area CA1 in learning of temporal structure by utilizing optogenetic manipulations combined with computational modelling of mouse behavior during this task. I will then use calcium imaging of individual neurons in dorsal and ventral CA1 to investigate the hippocampal representation of task related information during learning. Overall, our goal is to uncover how the hippocampus represents the abstract relationship between odour stimuli, and how this role differs across the dorsal to ventral axis of the hippocampus.