期刊
CELL REPORTS
卷 21, 期 4, 页码 910-918出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.09.087
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资金
- Simons Foundation [SFARI 314688, 400101]
- Brain and Behaviour Foundation (NARSAD Independent Investigator Grant) [25861]
- Italian Ministry of Education, University and Research (MIUR) (Prin) [200894SYW2]
- Toscana Life Sciences Foundation [Orphan_0108]
- Norwegian Research Council [ES464748]
- European Social Fund [2160_30052012_UNIPI-29]
Serotonin-producing neurons profusely innervate brain regions via long-range projections. However, it remains unclear whether and how endogenous serotonergic transmission specifically influences regional or global functional activity. We combined designed receptors exclusively activated by designed drugs (DREADD)-based chemogenetics and functional magnetic resonance imaging (fMRI), an approach we term chemo-fMRI,'' to causally probe the brain-wide substrates modulated by endogenous serotonergic activity. We describe the generation of a conditional knockin mouse line that, crossed with serotonin-specific Cre-recombinase mice, allowed us to remotely stimulate serotonergic neurons during fMRI scans. We show that endogenous stimulation of serotonin-producing neurons does not affect global brain activity but results in region-specific activation of a set of primary target regions encompassing corticohippocampal and ventrostriatal areas. By contrast, pharmacological boosting of serotonin levels produced widespread fMRI deactivation, plausibly reflecting the mixed contribution of central and perivascular constrictive effects. Our results identify the primary functional targets of endogenous serotonergic stimulation and establish causation between activation of serotonergic neurons and regional fMRI signals.
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