DEVELOPMENTAL DYNAMICS SHAPE THE ONTOGENY OF HIPPOCAMPUS-DEPENDENT MEMORIES

The ability to encode and store memories from personal experiences is crucial for an animal's survival and develops over a prolonged postnatal period. At first, this ability is restricted to the encoding of transient, generalized memories. With time, hippocampal-dependent memories acquire specificity and persistence, and support the successful execution of increasingly complex memory-based tasks. The mechanisms that support this increase in cognitive potential remain poorly understood, but have been linked to the maturation of specific neuronal circuits, including the entorhinal-hippocampal network.
A fundamental principle governing hippocampal circuit assembly is that new cohorts of neurons are integrated into the hippocampal network according to their birthdate. We recently discovered that hippocampal neurons with distinct birthdates (isochronic neurons) segregate into subpopulations with distinct physiological properties and contributions to memory processes in adult animals. Together, these findings raise the fundamental question of how developmental dynamics that lead to the staggered maturation of isochronic subpopulations influence the ontogeny of hippocampus-dependent memories.
Using targeted labeling of isochronic neurons, chemogenetics, histology, and calcium imaging, we show that developmental maturation sequences are mirrored in the recruitment of principal neurons to memory engrams. Infant memories bias hippocampal population dynamics toward early-born excitatory subnetworks during associative contextual encoding. In contrast, delayed recruitment of late-born neurons recapitulates the ontogeny of experience-dependent navigation and associative spatial memory, while shifting brain-wide cFos-defined networks from a developmental to a balanced, adult-like configuration. Together, our results suggest that hippocampal cell-type expansion during development increases cognitive potential by reshaping the recruitment of distributed neuronal networks.