Detection of a High-Turnover Serotonin Circuit in the Mouse Brain Using Mass Spectrometry Imaging.

Eiji Sugiyama,Yuki Sugiura,Kurara Honda,Mitsutoshi Setou,Matteo M Guerrini,Patrik Källback,Makoto Suematsu,Manabu Abe,Yuko Hattori,Kenji F Tanaka,Per E Andrén,Sidonia Fagarasan

doi:10.1016/j.isci.2019.09.036

Abstract

SummaryMonoamine neurotransmitters are released by specialized neurons regulating behavioral, motor, and cognitive functions. Although the localization of monoaminergic neurons in the brain is well known, the distribution and kinetics of monoamines remain unclear. Here, we generated a murine brain atlas of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels using mass spectrometry imaging (MSI). We found several nuclei rich in both 5-HT and a catecholamine (DA or NE) and identified the paraventricular nucleus of the thalamus (PVT), where 5-HT and NE are co-localized. The analysis of 5-HT fluctuations in response to acute tryptophan depletion and infusion of isotope-labeled tryptophan in vivo revealed a close kinetic association between the raphe nuclei, PVT, and amygdala but not the other nuclei. Our findings imply the existence of a highly dynamic 5-HT-mediated raphe to PVT pathway that likely plays a role in the brain monoamine system.

Highlights

Monoamine neurotransmitters are a family of small molecules that include serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA), and norepinephrine (NE), which are secreted by specific neuronal populations that regulate executive functions (Aston-Jones and Cohen, 2005; Lucki, 1998; Wise, 2004)
Numerous studies have shown that regional monoaminergic tuning directs behavior: that is, the depletion of 5-HT in the basolateral amygdala (BLA) reduces anxiety-like behaviors and weakens fear-associated memory (Johnson et al, 2015); the level of DA in the dorsal striatum is directly correlated to the adaptive changes of locomotion in a mouse model of Parkinson disease (Panigrahi et al, 2015); and reduced NE levels in the BLA increases the occurrence of anxiety-like behavior (McCall et al, 2017)
Generation of a Mouse Brain Atlas of 5-HT, DA, and NE We analyzed the coronal slices of a mouse brain prepared at an interval of 330 mm using mass spectrometry imaging (MSI) using an 8-weeks old C57BL/6J male mouse as a representative example (Figure 1)

Summary

Introduction

Monoamine neurotransmitters are a family of small molecules that include serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA), and norepinephrine (NE), which are secreted by specific neuronal populations that regulate executive functions (Aston-Jones and Cohen, 2005; Lucki, 1998; Wise, 2004). Considering their essential roles in controlling goal-directed and adaptive behavior, the abundance and localization of monoamine neurotransmitters in the brain must be tightly controlled. We assumed that the direct detection of monoamine levels in the brain may be a powerful and unbiased approach to identify the intensity and kinetics of monoaminergic signaling targeting different brain regions

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Conclusion