Comprehensive Topographical Map of the Serotonergic Fibers in the Mouse Brain

Abstract

24 It is well established that serotonergic fibers distribute throughout the brain. Abnormal 25 densities or patterns of serotonergic fibers have been implicated in neuropsychiatric disorders.26 Although many classical studies have examined the distribution pattern of serotonergic fibers, 27 most of them were either limited to specific brain areas or had limitations in demonstrating the 28 fine axonal morphology. In this study, we utilize transgenic mice expressing GFP under the 29 SERT promoter to map the topography of serotonergic fibers across the rostro-caudal extent of 30 each brain area. We demonstrate previously unreported regional density and fine-grained 31 anatomy of serotonergic fibers. Our findings include: 1) SERT fibers distribute abundantly in 32 the thalamic nuclei close to the midline and dorsolateral areas, in most of the hypothalamic 33 nuclei with few exceptions such as the median eminence and arcuate nuclei, and within the 34 basal amygdaloid complex and lateral septal nuclei, 2) the source fibers of innervation of the 35 hippocampus traverse through the septal nuclei before reaching its destination, 3) unique, 36 filamentous type of straight terminal fibers within the nucleus accumbens, 4) laminar pattern 37 of innervation in the hippocampus, olfactory bulb and cortex with heterogenicity in innervation 38 density among the layers, 5) cortical labelling density gradually decreases rostro-caudally, 6) 39 fibers traverse and distribute mostly within the gray matter, leaving the white fiber bundles 40 uninnervated, and 7) most of the highly labelled nuclei and cortical areas have predominant 41 anatomical connection to limbic structures. In conclusion, we provide novel, regionally specific 42 insights on the distribution map of serotonergic fibers using transgenic mouse.