Divergent innervation of the olfactory bulb by distinct raphe nuclei

Abstract

The raphe nuclei provide serotonergic innervation widely in the brain, thought to mediate a variety of neuromodulatory effects. The mammalian olfactory bulb (OB) is a prominent recipient of serotonergic fibers, particularly in the glomerular layer (GL), where they are thought to gate incoming signals from the olfactory nerve. The dorsal raphe nucleus (DRN) and the median raphe nucleus (MRN) are known to densely innervate the OB. The majority of such projections are thought to terminate in the GL, but this has not been explicitly tested. We sought to investigate this using recombinant adeno-associated viruses (rAAV)-mediated expression of green fluorescent protein (GFP)-synaptophysin targeted specifically to neurons of the DRN or the MRN. With DRN injections, labeled fibers were found mostly in the granule cell layer (GCL), not the GL. Conversely, dense labeling in the GL was observed with MRN injections, suggesting that the source of GL innervation is the MRN, not the DRN, as previously thought. The two raphe nuclei thus give dual innervation within the OB, with distinct innervation patterns. J. Comp. Neurol. 523:805–813, 2015. © 2015 Wiley Periodicals, Inc.

Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning after Targeting Adult Brain Serotonin Synthesis

“…2 D ). Particularly in the olfactory bulb, the massive amounts of anti–5-HT fibers originating in the MRN and terminating in the glomerular layer (McLean and Shipley, 1987; Steinfeld et al, 2015; Suzuki et al, 2015; Muzerelle et al, 2016), the first synaptic processing layer of odor information, were absent in AAV-Cre–injected Tph2 fl/fl mice (Fig. 2 D ).…”

“…2 A ). In adult Tph2 fl/fl mice, AAV-Cre or AAV-GFP was injected into the midbrain, where 5-HT neurons of the MRN/DRN are located and project to olfactory structures in the forebrain (McLean and Shipley, 1987; Steinfeld et al, 2015). …”

“…The mammalian olfactory system is innervated by 5-HT neurons into both its primary and secondary odor processing stages (McLean and Shipley, 1987; Smith et al, 1993; Steinfeld et al, 2015; Suzuki et al, 2015). Midbrain 5-HT neurons located in the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) innervate the olfactory bulb, where fibers are observed in several cell layers (McLean and Shipley, 1987; Steinfeld et al, 2015; Suzuki et al, 2015; Muzerelle et al, 2016), including surrounding the glomeruli, which represent the first synaptic processing stage of odor information.…”

Serotonin increases synaptic activity in olfactory bulb glomeruli

“…The olfactory bulb (OB) receives dense serotonergic innervation, particularly from the median raphe to the glomerular layer (McLean and Shipley 1987;Steinfeld et al 2015), but relatively little is known about 5HT modulation of glomerular circuits. Glomeruli are the first site of synaptic processing for odorant signals from the olfactory epithelium.…”

Flexible Representations of Odour Categories in the Mouse Olfactory Bulb

“…In comparison to other sensory regions at a similar level of the hierarchy, the OB receives massive feedback projections from cortical, subcortical [38][39][40][41][42][43][44][45][46] and neuromodulatory centres [47][48][49]. These regions may convey back to the OB information that is not primarily sensory.…”