Serotonergic afferents to the rat olfactory bulb: I. Origins and laminar specificity of serotonergic inputs in the adult rat

Abstract

This is a study of the chemoanatomical organization of the projection from the raphe nuclei to the main olfactory bulb in the rat. A heavy projection from the dorsal and median raphe nuclei to the main olfactory bulb was shown by both retrograde and anterograde tracing techniques. Following injections of 1% wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the main olfactory bulb, up to 1300 neurons were retrogradely labeled in the dorsal and median raphe nuclei, a much larger number than has been suggested by previous studies. By combining 5-HT immunofluorescence with True blue retrograde fluorescent labeling, it was determined that the vast majority of raphe neurons that project to the olfactory bulb contain serotonin. Injections of WGA-HRP into dorsal and/or median raphe produced dense anterograde labeling in the glomeruli, while fewer labeled fibers were observed in the external plexiform layer, internal plexiform layer, and granule cell layer. In contrast to the number of other centrifugal afferents to the bulb, a significant contingent of fibers from the raphe nuclei enters the main olfactory bulb (MOB) from outside in, i.e., via the olfactory nerve layer. Serotonergic fibers in MOB were visualized by immunocytochemistry, and the distribution of specific 5-HT fibers closely matched the distribution of anterograde terminal label resulting from injections of WGA-HRP in the raphe nuclei. The serotonergic fibers have a specific laminar distribution and morphology in MOB. Thus, the density of the serotonergic innervation to the glomerular layer is 2-3 times that of any other layer in MOB. In addition to their preferential innervation of the glomeruli, glomerular and infraglomerular serotonergic fibers are morphologically different. Serotonergic fibers located in the glomerular layer are generally thick (0.25-0.60 micron) compared to the thinner (0.25-0.35 micron) fibers that predominate in infraglomerular layers. Another difference is that the glomerular fibers often contain varicosities that are greater than 1 micron in diameter, while varicosities along infraglomerular fibers are usually barely larger than the axonal diameter. Finally, glomerular fibers are much more intensely stained than infraglomerular fibers. Electrolytic lesions of the dorsal and median raphe caused a total depletion of serotonin fiber staining in the bulb, demonstrating that the raphe nuclei are the sole source of the serotonergic input to the main olfactory bulb. Thus, it has been demonstrated that serotonergic neurons in dorsal and median raphe project very heavily to glomeruli and less heavily to other layers in the main olfactory bulb.(ABSTRACT TRUNCATED AT 400 WORDS)

Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects

“…Once crossed the semi-permeable nasal blood-brain barrier, C-1A-siRNA molecules may reach the dense plexus of serotonergic axons in outer layers of the olfactory bulb, anatomically connected with olfactory regions. 45 In summary, our results show for the first time the feasibility of using RNAi …”

Serotonergic influence on olfactory learning in the neonate rat

“…However, the finding that serotonin is involved in conditioned olfactory learning at all is important because it provides a role for 5-HT in olfaction. In the past, very little has been known about the functional role of 5-HT in the bulb even though the serotonergic innervation to that structure is dense (McLean & Shipley, 1987b) and arrives at a time when many developmental processes are occurring (McLean & Shipley, 1987a). Thus, one would expect 5-HT to have modulatory effects over olfactory information at the earliest levels of synaptic processing in the CNS and this study suggests that this is the case.…”

“…was used to detect intrinsic dopaminergic cells of the olfactory bulb. Dilutions of the primary antibodies and secondary visualization methods have been described previously (McLean, Shipley, Nickell, Aston-Jones, & Reyher, 1989;McLean & Shipley, 1987b.…”

“…Indeed, we have found that lack of serotonergic input to the developing olfactory bulb has very little, if any, effect on the cytoarchitecture of that structure (McLean, 1991), even though other studies have suggested such a role in the developing neocortex (Lauder, Wallace, Krebs, Petrusz, & McCarthy, 1982;Lauder, 1990). However, the fact that 5-HT begins to proliferate in the olfactory bulb during the first week of postnatal life (McLean & Shipley, 1987a) and richly innervates the bulb in the adult rat (McLean & Shipley, 1987b) suggests that it has a developmental/functional role in olfaction that begins during early postnatal life. A functional role for 5-HT in the bulb is especially probable since the glomeruli, the first site of transfer of olfactory information from the nose to the CNS, is the most densely innervated serotonergic target in the bulb of the rat (McLean & Shipley, 1987a).…”

Behavioral State Regulation of Dendrodendritic Synaptic Inhibition in the Olfactory Bulb

“…The OB receives centrifugal inputs from neuromodulatory systems, including cholinergic (Ichikawa and Hirata, 1986), noradrenergic (McLean et al, 1989), and serotonergic (McLean and Shipley, 1987) systems. The activity of the neuromodulatory systems changes with the behavioral state of the animal.…”