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实验室

10:00-11:00, Tuesday, October 23, 2018


Speaker: Jing Ren, Ph.D.

Biology Department, Stanford University

Topic: Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems

Host:  Minmin Luo, Ph.D.

Abstract

The serotonin system powerfully modulates physiology and behavior in health and disease. It is the most widely used pharmacological target for treating depression and anxiety, and depression has become the leading cause of disability. However, a physiological and circuitry-based theory of how the serotonin system is organized to carry out its diverse functions remains elusive. The dorsal raphe (DR) nucleus is the predominant source of serotonergic innervation of the forebrain and modulates diverse functions and brain states. Most functional studies to date have treated DR serotonin neurons as a single population, and a consensus on the primary functions of the DR serotonin system is lacking.

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.