Two types of locus coeruleus neurons born on different embryonic days in the mouse.

Retrograde axonal tracing studies were performed in combination with tritiated thymidine cell birthday analyses in order to determine whether or not any hodologicotemporal gradients exist in neuron genesis within the murine locus coeruleus. Following injections of retrograde tracers within the forebrain or cerebellum in mice exposed in utero to the radiolabeled nucleoside on embryonic days 9-11 (E9-11), combined histochemical and autoradiographic preparations revealed: 1) Locus coeruleus neurons that give rise to long distance axonal projections to the cortices are born exclusively on E9 (other studies indicate that these cells are noradrenergic); and 2) Locus coeruleus cells born on E10 and E11 are a class of smaller cells which were never observed to project to distant structures. The transmitters of these apparent local circuit neurons have not yet been determined, but gamma aminobutyric acid is one possible candidate. These findings support the interpretation that monoaminergic neurons tend to arise earlier during development than non-monoaminergic neurons within the locus coeruleus, and that distinctly different connectional arrangements exist for these monoaminergic and non-monoaminergic cells.