CHOLINERGIC AND OXYTOCINERGIC NEUROMODULATION IN THE DEVELOPING HIPPOCAMPUS

Subcortical neuromodulators regulate adult hippocampal circuit function. Among them, cholinergic and oxytocinergic neuromodulatory systems were recently shown to cooperate and differentially affect population synchrony in the adult CA1 region (Zhang et al. 2024). While synchronous population activity is a hallmark of developing hippocampal circuits and instrumental for their proper wiring, the anatomical and functional developmental timelines of these two inputs remain unknown. At the anatomical level, we use a combination of immunohistochemistry and spatial transcriptomics to track their spatiotemporal patterns of development during the first weeks of postnatal mouse development. We show that these two pathways converge onto a specific subtype of GABAergic neuron. At the functional level, we use two-photon dual-color calcium imaging to demonstrate that acetylcholine and oxytocin release correlate with animal behavior and single neuron activity across development. Finally, we manipulate both of these neuromodulatory systems using opto- and chemogenetics. Together, our results suggest that cholinergic and oxytocinergic neuromodulation contributes to the early maturation and functional organization of hippocampal networks, possibly by coordinating the activity of key neurons during a critical developmental window.