"In the central nervous system, 5-hydroxytryptamine (5-HT, or serotonin) acts as a neuromodulator and is synthetized by a specific population of neurons. 5-HT is released in nearly all subdivisions of the CNS and is involved in a wide array of brain functions as well as in several disorders. Although current hypotheses regarding the role of central 5-HT remain wide-ranging, a prominent view has progressively emerged from previous studies. A primary function of 5-HT might be to dampen sensory information processing while facilitating motor output. This ""sensorimotor gating"" hypothesis is supported by indirect evidence and has never been tested directly. This proposal aims at investigating the influence of 5-HT on olfactory performance. By using mice expressing a recently developed light-gated cation channel (Channelrhodopsin-2) in serotonergic neurons, we will be able to excite serotonergic afferents to the olfactory bulb through a fiber optic interface. Using this innovative method, we will interfere with the native modulation pattern of these afferents during olfactory discrimination. The effects of this manipulation will be assessed directly at the behavioral level. This novel experimental paradigm offers tremendous improvements compared to previous ones and is expected to provide unprecedented insights into the role of central 5-HT in sensory processing."
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