Locus coeruleus - cerebellum: interaction during development

The presentation describes a combined morphological and biochemical analysis of the developmental interaction between the locus coeruleus (LC) and the cerebellum of rats, which receives an afferent innervation from the LC. The LC neurons are among the first CNS neurons to arise during ontogeny. They establish axonal connections to their target areas while migrating into their nuclear area, where they collect around E17. Their perikaryal development proceeds through the well-known stages of neuronal differentiation, Nissl body formation as a sign of synaptic connectivity appearing for the first time on E18. However, changes in the LC-perikarya are taking place in early postnatal stages. Perikaryal volume increases to reach a transitory maximum of 150% of the adult value on P15. Ultrastructurally, a dissolution of Nissl bodies and an increase in the number of polyribosomes are seen during this developmental period, reminiscent of perikaryal changes during the axon reaction. Later, the organization of ribonucleoproteins into Nissl bodies is re-established. NA axons are demonstrable in the cerebellar anlage for the first time on E17. They increase rapidly in number and organization during cerebellar development as shown by catecholamines histofluorescence. Quantitative measurements of cerebellar high-affinity uptake for NA show that a peak of NA innervation is reached on P10, which amounts to about 250% of the adult value. This hyper-innervation is transitory and declines to adult values on P20. The period of cerebellar NA hyperinnervation corresponds to the perikaryal changes in volume and ultrastructure of LC neurons. The phenomenon of transitory hyperinnervation of a target area is discussed with respect to the establishment of axonal connections during normal development and in regeneration.