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Séminaire - Minmin LuoReward signaling by the dorsal raphe

Abstract :

Une invitation de Giovanni Marsicano du Neurocentre Magendie


The dorsal raphe nucleus (DRN) is the major source of 5-HT for the forebrain.
The 5-HT signaling pathway has been implicated in numerous behavioral processes related to cognition, emotion, mood, sensory processing, and motor activity. However, the exact behavioral functions of DRN neurons remain mysterious. Here, I will describe our recent data that demonstrate the capability of DRN neurons to provide strong reward signals. Optogenetic stimulation of DRN Pet-1 neurons potently reinforces animal behavior, efficiently guide animal learning, and rapidly reshape the activity pattern of cortical neurons. Recordings from head-fixed mice and freely behaving mice reveal that DRN neurons encode both reward expectation and consumption. Although DRN Pet-1 neurons are commonly associated with 5-HT, they release both glutamate and 5-HT. In addition, behavioral assays on mutant mice show that both glutamate and 5-HT contribute to reward signaling. These results suggest that the DRN is a key brain center for reward processing, and shed new lights into the reward theory and therapeutic interventions of depression and anhedonia. 

Selected publications

Dorsal raphe neurons signal reward through 5-HT and glutamate.
Liu Z, Zhou J, Li Y, Hu F, Lu Y, Ma M, Feng Q, Zhang JE, Wang D, Zeng J, Bao J, Kim JY, Chen ZF, El Mestikawy S, Luo M.
Neuron. 2014 Mar 19;81(6):1360-74. doi: 10.1016/j.neuron.2014.02.010.

Selective activation of cholinergic basal forebrain neurons induces immediate sleep-wake transitions.
Han Y, Shi YF, Xi W, Zhou R, Tan ZB, Wang H, Li XM, Chen Z, Feng G, Luo M, Huang ZL, Duan S, Yu YQ.
Curr Biol. 2014 Mar 17;24(6):693-8. doi: 10.1016/j.cub.2014.02.011. Epub 2014 Mar 6.

Pharmacogenetic activation of midbrain dopaminergic neurons induces hyperactivity.
Wang S, Tan Y, Zhang JE, Luo M.
Neurosci Bull. 2013 Oct;29(5):517-24. doi: 10.1007/s12264-013-1327-x. Epub 2013 Mar 20.

Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively.
Zhan C, Zhou J, Feng Q, Zhang JE, Lin S, Bao J, Wu P, Luo M.
J Neurosci. 2013 Feb 20;33(8):3624-32. doi: 10.1523/JNEUROSCI.2742-12.2013.

Scientific focus :

http://www.nibs.ac.cn/en/pi/luominmin.html

The mammalian central nervous system is broadly innervated by many aminergic modulatory neurotransmitters, the malfunctions of which are closely related to many human psychiatric disorders. My laboratory studies the physiological mechanisms underlying the regulation of reward, learning, anxiety, movement, arousal level, and sleep behaviors by dopamine, 5-HT, norepinephrine, and acetylcholine neurons in the brainstem. By combining electrophysiology, optogenetics, mouse genetics, and behavioral assays, we investigate how the modulatory neurons change their activity patterns during different behavioral contexts and how manipulating neuronal activity influences animal behaviors. To dissect the molecular and cellular mechanisms underlying the modulation of these 'modulatory neurons', we also record the physiological and pharmacological properties of these neurons in acute brain slices. Our studies not only have the potentials of contributing to the understanding of neural mechanisms of some fundamental animal behaviors but also may facilitate clinical efforts toward the cure of human psychiatric disorders.

 

Giovanni Marsicano (giovanni.marsicano @ googlemail.com)