Comprehensive topographical map of the serotonergic fibers in the male mouse brain

Abstract

It is well established that serotonergic fibers distribute throughout the brain. Abnormal densities or patterns of serotonergic fibers have been implicated in neuropsychiatric disorders. Although many classical studies have examined the distribution pattern of serotonergic fibers, most of them were either limited to specific brain areas or had limitations in demonstrating the fine axonal morphology. In this study, we utilize male mice expressing green fluorescence protein under the serotonin transporter (SERT) promoter to map the topography of serotonergic fibers across the rostro-caudal extent of each brain area. We demonstrate previously unreported regional density and fine-grained anatomy of serotonergic fibers. Our findings include: (a) SERT fibers distribute abundantly in the thalamic nuclei close to the midline and dorsolateral areas, in most of the hypothalamic nuclei with few exceptions such as the median eminence and arcuate nuclei, and within the basal amygdaloid complex and lateral septal nuclei, (b) the source fibers of innervation of the hippocampus traverse through the septal nuclei before reaching its destination, (c) unique, filamentous type of straight terminal fibers within the nucleus accumbens, (d) laminar pattern of innervation in the hippocampus, olfactory bulb and cortex with heterogenicity in innervation density among the layers, (e) cortical labeling density gradually decreases rostro-caudally, (f) fibers traverse and distribute mostly within the gray matter, leaving the white fiber bundles uninnervated, and (g) most of the highly labeled nuclei and cortical areas have predominant anatomical connection to limbic structures. In conclusion, we provide novel, regionally specific insights on the distribution map of serotonergic fibers using transgenic mouse.

Densities and numbers of calbindin and parvalbumin positive neurons across the rat and mouse brain

“…The distribution of cells types, neurotransmitter receptors, and axonal connections varies substantially across different cortical and subcortical areas (see, e.g. Awasthi et al, 2020 ; Yu et al., 2019b ). Such diversity occurs at multiple levels, from microcircuits to large-scale patterns across brain areas ( Caroni, 2015 ; Kim et al., 2017 ), and specific combinations of multiple neurotransmitter receptors and cell types have been proposed to underlie specific functional characteristics of regions and networks ( Zilles et al., 2015 ).…”

Serotonin neurons modulate learning rate through uncertainty

“…5,8,24 One such system comprises a small number of serotonin-releasing neurons (on the order of 10 4 in mice) 25 with extensive axonal projections. This small group of cells affects large numbers of neurons in distributed regions [26][27][28][29] that are responsible for learning and decision making. The activity of these neurons changes on behaviorally relevant timescales-both fast (hundreds of milliseconds) and slow (tens of seconds).…”

BDNF Alterations in Brain Areas and the Neurocircuitry Involved in the Antidepressant Effects of Ketamine in Animal Models, Suggest the Existence of a Primary Circuit of Depression

“…Consequently, since diminished motivation is an essential feature of depression [28], it is likely that it is extensively involved both in developing and sustaining depression as well as in the mechanism of action of StAD and ketamine [19,24,177]. The BNST's role in anxiety and depression is also evidenced by a serotonergic innervation of the BNST [178,179]; interestingly, the availability of serotonin reuptake sites in the BNST is positively correlated with individual differences in anxiety behaviour [180]. The BNST receives glutamatergic projections from the mPFC, from the hippocampus and the basomedial amygdale, whereas GABAergic inputs arise from central and medial amygdaloid nuclei [181] (Fig.…”