Functional segregation of hippocampal subdivisions in learning and memory

Abstract

The hippocampus is well known for its function in declarative memories, especially in episodic memories and spatial navigation. Considering strikingly different features along its longitudinal axis from dorsal to ventral hippocampus, it has been proposed that hippocampal subdivisions might have distinct functional roles. Among several hypotheses, a particular prominent one is that dorsal hippocampus is required for cognitive functions, while ventral hippocampus is involved in emotional learning and stress responses, but their precise roles in learning and memory have remained controversial. In this thesis, I further explore the idea of a functional segregation, focusing on the roles of dorsal and ventral hippocampus in different types of declarative memories. Therefore, I use chemogenetic silencing to locally interfere with subdivision function in reinforced and incidental learning at various time points after memory acquisition and at memory retrieval. First, I compare the functions of dorsal and ventral hippocampus in single-trial learning. Then, I am addressing their roles in the formation of associations to previously acquired memories. Moreover, applying chemogenetic silencing and powerful recently developed techniques to genetically target learning-related neuronal populations, I study the localization of single-trial and association memories within the hippocampus. I show how in all hippocampus-dependent tasks both dorsal and ventral hippocampus is required, but with distinct contributions and irrespective of emotional relevance. Specifically, ventral hippocampus is involved in forming and recalling primary associations, whereas dorsal hippocampus is particularly important during a window of 5h post new learning. During this window dorsal hippocampus recalls memories and forms secondary associations learned on top of previously acquired memories. Thereby, the subdivisions provide a mechanism to recall previously acquired memories and to form associations to them without interference of memories, but instead with the possibility to independently use the distinct memory components. In a supplementary part, I have started to investigate the function of the transversal hippocampal axis, in particular the dentate gyrus in association learning. This study allows a first insight into a possible mechanism that might shape memory assemblies to form associations.