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Cell. 2018 Oct 4;175(2):472-487.e20. doi: 10.1016/j.cell.2018.07.043. Epub 2018 Aug 23.

Anatomically Defined and Functionally Distinct Dorsal Raphe Serotonin Sub-systems.

Author information

1
Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
2
Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
3
Department of Neurology and Neurological Sciences, Stanford, CA 94305, USA.
4
Department of Physics, Stanford University, Stanford, CA 94305, USA.
5
Delivery Technology Core, Massachusetts General Hospital, Cambridge, MA 02139, USA.
6
Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: lluo@stanford.edu.

Abstract

The dorsal raphe (DR) constitutes a major serotonergic input to the forebrain and modulates diverse functions and brain states, including mood, anxiety, and sensory and motor functions. Most functional studies to date have treated DR serotonin neurons as a single population. Using viral-genetic methods, we found that subcortical- and cortical-projecting serotonin neurons have distinct cell-body distributions within the DR and differentially co-express a vesicular glutamate transporter. Further, amygdala- and frontal-cortex-projecting DR serotonin neurons have largely complementary whole-brain collateralization patterns, receive biased inputs from presynaptic partners, and exhibit opposite responses to aversive stimuli. Gain- and loss-of-function experiments suggest that amygdala-projecting DR serotonin neurons promote anxiety-like behavior, whereas frontal-cortex-projecting neurons promote active coping in the face of challenge. These results provide compelling evidence that the DR serotonin system contains parallel sub-systems that differ in input and output connectivity, physiological response properties, and behavioral functions.

KEYWORDS:

5-HT; Tph2; Vglut3; anxiety; central amygdala; depression; dorsal raphe; fiber photometry; iDISCO; orbital frontal cortex; serotonin

PMID:
30146164
PMCID:
PMC6173627
[Available on 2019-10-04]
DOI:
10.1016/j.cell.2018.07.043
[Indexed for MEDLINE]

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