Developmental origins of central norepinephrine neuron diversity.

Anthony Pickering

Anthony Pickering

Anthony Pickering

Stefan Hirschberg

Stefan Hirschberg

Stefan Hirschberg

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This article reveals the origin and connectivity of noradrenergic brainstem neurons, based on their embryonic gene-expression history, using a transgenic mouse line approach. Noradrenaline acts throughout the neuraxis to modulate various processes such as memory, reward, arousal and autonomic homeostasis. All central noradrenaline originates from anatomically defined clusters of neurons in the brainstem that have extensive axonal projections. Robertson et al. generated several mouse lines that label noradrenergic neurons derived from specific rhombomere progenitor classes. With this lineage-based specificity, the authors show that neurons sharing the same gene-expression history are spread across the conventional neuroanatomical divisions of the noradrenergic cell groups. Using this approach, they show the rhombomere-based groups have differing projection targets and even distinct axonal morphologies. They also reveal a little-appreciated noradrenergic projection to prefrontal cortical areas from outside of the locus coeruleus progenitor domain. Their domain-specific recombinase driver lines also offer the opportunity to manipulate genetically defined subdivisions of the noradrenergic system and to study their functional roles in vivo.