Brain-wide Mapping of Endogenous Serotonergic Transmission via Chemogenetic fMRI

• DOI: 10.1016/j.celrep.2017.09.087
• Publication Date: 2017-10-26T14:20:33Z
• Authors: Andrea Giorgi; Sara Migliarini; Alberto Galbusera; Giacomo Maddaloni; Maddalena Mereu; Giulia Margiani; Marta Gritti; Silvia Landi; Francesco Trovato; Sine Mandrup Bert...; Andrea Armirotti; Gian Michele Ratto; Maria Antonietta ...; Raffaella Tonini; Alessandro Gozzi; Massimo Pasqualetti
• Keywords: Brain mapping

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 drugs (DREADD)-based chemogenetics magnetic resonance imaging (fMRI), an approach we term "chemo-fMRI," to causally probe the brain-wide substrates modulated describe generation of a conditional knockin mouse line that, crossed with serotonin-specific Cre-recombinase mice, allowed us remotely stimulate during fMRI scans. show that stimulation serotonin-producing does not affect activity but results in region-specific activation set primary target encompassing corticohippocampal ventrostriatal areas. By contrast, pharmacological boosting serotonin levels produced widespread deactivation, plausibly reflecting mixed contribution central perivascular constrictive effects. Our identify targets establish causation between signals.