Noradrenergic Modulation of Hippocampal Post-Natal Development

Many brain disorders with cognitive impairment originate during development, when synaptic and neuromodulatory circuits progressively emerge, mature and give rise to function. In the hippocampus, stereotyped sequences of brain activity patterns in early life are thought to set the stage for coherent cognitive and memory processes in adulthood, for which noradrenaline neuromodulation is also critical. However, surprisingly little is known about the developmental origins of hippocampal neuromodulation in general, and of noradrenaline transmission in particular, neither in health nor disease. In project HIPPNADEV, I will investigate the contribution of noradrenergic transmission to the post-natal development of the hippocampus: In other words, “if”, “when” and “how” noradrenergic signals acquire their cellular and circuit-level properties in the developing hippocampus. I will use a highly innovative, translationally relevant, multi-disciplinary and multi-scale approach, combining in mice anatomical and functional interrogation using cutting-edge technology including spatial transcriptomics and in vivo all-optical dual imaging of noradrenaline release and single-neuron calcium activity. Further, this project will compare the developmental trajectories and functional significance of hippocampal noradrenergic signals at baseline and in rodent models of schizophrenia. Altogether, it will significantly advance our understanding of hippocampal neurodevelopment on one hand – implicating neuromodulatory noradrenergic transmission therein – and vice versa elucidate still-unknown developmental aspects of noradrenaline transmission. Such breakthroughs will offer promising bases for future fundamental study of the neuromodulatory correlates of neurodevelopment, as well as a solid preclinical framework to better combat schizophrenia syndromes and associated psychoses.