Postnatal development of the noradrenergic projection from locus coeruleus to the olfactory bulb in the rat

Norepinephrine (NE) may play a role in the developing brain by modulating synaptic plasticity during critical periods of circuit formation (Kasamatsu and Pettigrew, 1976; 1979; Bear and Singer, 1986). In the olfactory bulb, NE input from the locus coeruleus (LC) appears to be necessary for the newborn rat to form a learned odor preference (Sullivan and Leon, 1986; Wilson and Leon, 1988; Sullivan et al., 1989). However, little is known about the development of NE innervation of the olfactory bulb. Thus, it is not clear how the maturation of the LC projection to the bulb correlates with the formation of olfactory bulb circuits during the period when NE modulates early olfactory learning. In this study, the postnatal development of the NE input from the LC to the main and accessory bulbs was characterized with tract tracing, immunocytochemistry, and quantitative image analysis methods. By birth there is already a substantial input to the olfactory bulb from the LC; as many as 200 LC neurons can be retrogradely labelled with wheatgerm agglutinin-horseradish peroxidase injection in the olfactory bulb. This compares with an estimated 400-600 neurons labelled by similar procedures in adult rats (Shipley et al., 1985). In order to study the development of NE fibers innervating the olfactory bulb, immunocytochemistry with antibodies to dopamine-beta-hydroxylase was employed. Image analysis was used to facilitate visualization and to quantitate the development of fiber densities. At birth, immunocytochemically labelled NE fibers were identified in all layers of the main and accessory olfactory bulb. The innervation was strongly preferential for infraglomerular layers at all stages of postnatal development. The fibers were densest in the internal plexiform and granule cell layers, less dense in the external plexiform layer, and sparse in the glomerular layer. The density of the fibers increased during development. There were no significant shifts in the relative distribution of the fibers in different layers of the bulb during development. This consistent laminar innervation by NE fibers suggests that if these fibers have a developmental role, their influence is probably limited to neuronal elements in inframitral cell layers.