Lay summary

The hippocampal formation is essential for the processing of declarative memory, which includes the representation of unique personal experiences called episodic memories and the memory for facts about the world called semantic memories. In humans, significant changes in the capacity for declarative memory occur within the first 3-7 years of life, but the neurobiological basis for such changes had remained highly hypothetical. In the last few years, however, our own studies have demonstrated that distinct regions, layers and cells of the hippocampal formation exhibit different profiles of structural development during early postnatal life. Together with functional studies of memory, our findings suggested how the differential maturation of distinct hippocampal circuits might underlie the emergence of specific "hippocampus-dependent" memory processes, culminating in the emergence of episodic memory concomitant with the maturation of all hippocampal circuits.

This application builds on the results obtained in previous years and will contribute to approaching our long-term goal of understanding the development, plasticity and function of the primate hippocampal formation.

In the first project, we will test the hypothesis that distinct layers and subdivisions of the primate entorhinal cortex, which contribute to different hippocampal functional circuits, exhibit differential maturation during early postnatal development. We already obtained preliminary evidence showing that the superficial layers II and III mature earlier that the deep layers V and VI. This suggests that although neocortical inputs can reach and be processed within hippocampal circuits relatively early, hippocampus output might be directed preferentially toward subcortical structures at early ages, and only reach neocortical areas at later stages of postnatal development.

In the second project we will test the hypothesis that, following neonatal hippocampal damage, the medial temporal lobe memory system undergoes structural and functional reorganization to enable the acquisition of long-term spatial memories. We have already found preliminary evidence of such reorganization at both structural (neuroanatomical tracers) and functional (immediate-early gene experiments) levels.