Olfactory Circuits for Reproduction and Reward

用于繁殖和奖励的嗅觉回路

• 批准号: 8374412
• 负责人: JAMES A. CHERRY
• 金额: $ 28.29万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-05 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8374412
• 关键词: Accessory Olfactory Bulbs; Adult; Affect; Afferent Neurons; Alleles; Amygdaloid structure; Animals; Area; Auditory; Axon; Behavior; Biological Preservation; Brain; Brain Part; Brain region; Cations; Cell Nucleus; Cells; Cholera Toxin; Cognitive; Cues; Data; Discrimination; Dopaminergic Cell; Dorsal; Environment; Estrus; Exposure to; Failure; Female; Fiber; Future; Goals; Gonadal Steroid Hormones; Heterogeneity; Histocompatibility; Hormones; Human; Human Pheromones; Human body; Hypothalamic structure; Image; Incentives; Injection of therapeutic agent; Label; Laboratories; Lesion; Link; Location; Mammals; Maps; Medial; Mediating; Motivation; Mus; Neural Pathways; Neurons; Neurosecretory Systems; Nose; Odors; Olfactory Cortex; Olfactory Epithelium; Olfactory Pathways; Partner in relationship; Pathway interactions; Pattern; Peripheral; Preparation; Process; Prosencephalon; Psychological reinforcement; Reporting; Reproduction; Research; Rewards; Route; Sensory; Sex Characteristics; Sexual Arousal; Sexual Partners; Signal Transduction; Site; Social Perception; Stereotyping; Stimulus; Structure of terminal stria nuclei of preoptic region; System; TRPM5 gene; Testing; Testosterone; Time; Tracer; Ventral Tegmental Area; Visual; Woman; base; exposed human population; insight; male; men; mesolimbic system; neuronal cell body; olfactory bulb; preference; relating to nervous system; reproductive; response; sensor; sex; social communication; transcription factor; urinary; ventromedial hypothalamic nucleus

In humans exposure to body odorants can produce sex-specific neuroendocrine responses, permit the discrimination of scents based on differences in major histocompatibility alleles, and sex-dependently activate regions of the hypothalamus involved in reproduction. However, failure to identify the neural pathways through which such signals access reproductive circuits has impeded our understanding of how human "pheromones" may affect behavior. Moreover, despite evidence in animals that such biologically relevant odors may act as natural rewards, the routes through which odors are conveyed to the mesolimbic dopamine system that mediates reinforcement have yet to be identified. Using mice, we have identified a direct projection of the main olfactory bulb (MOB) to the medial amygdala (Me), which projects to areas in the hypothalamus that control reproduction. Preservation of this pathway in humans could explain how odors influence sex partner preference and mating behavior. As chemosignals can be detected by both the main and accessory olfactory systems in the mouse, we will compare the involvement of each system in regulating responses to olfactory cues that control sexual motivation and reward. First, we will determine whether the direct pathway from the ventral MOB to the Me is differentially activated by male and female urinary volatiles in the two sexes and whether adult exposure to testosterone modulates the intensity of such responses. Next we will determine whether a subset of olfactory sensory neurons that express the M5 subtype of a TRP cation channel project to MOB glomeruli that are innervated by Me projecting mitral cells and selectively respond to opposite-sex urinary volatiles. Because we have observed that many of the ventral MOB projections to the Me also send branches to the olfactory cortex, we will map the targets of these projections to determine if specific sites in the olfactory cortex are preferentially innervated and differ in males and females. Choi et al (2005) suggested that odors of reproductive significance in mice activate a circuit of neurons that express the transcription factor, Lhx6, in the Me and bed nucleus of the stria terminalis (BNST) and then terminate in the ventromedial hypothalamic nucleus (VMH). We will determine the extent to which main vs accessory olfactory inputs selectively induce Fos (a marker of neuronal activity) in Lhx6- expressing neurons in the Me, BNST and VMH of male mice, and determine whether these neurons send axons to the ventral tegmental area, the location of dopaminergic cell bodies of the mesolimbic system. Finally, we will use a conditioned place preference paradigm to compare the incentive qualities of body odorants detected by the main vs accessory systems in male mice. Our results should provide insight into the olfactory and limbic circuits that process reproductively salient odor cues, and may also help elucidate the mechanism whereby non-olfactory (visual, auditory, or purely cognitive) inputs control sex partner preference and sexual arousal in humans.

在人体暴露于体味可以产生特定性别的神经内分泌反应，允许

项目成果

A sex comparison of the anatomy and function of the main olfactory bulb-medial amygdala projection in mice.

• DOI: 10.1016/j.neuroscience.2010.11.003
• 发表时间: 2011-01-13
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Kang, N.;McCarthy, E. A.;Cherry, J. A.;Baum, M. J.
• 通讯作者: Baum, M. J.

DREADD-induced silencing of the medial amygdala reduces the preference for male pheromones and the expression of lordosis in estrous female mice.

• DOI: 10.1111/ejn.13636
• 发表时间: 2017-08
• 期刊: The European journal of neuroscience
• 作者: McCarthy EA;Maqsudlu A;Bass M;Georghiou S;Cherry JA;Baum MJ
• 通讯作者: Baum MJ

Optogenetic Activation of Accessory Olfactory Bulb Input to the Forebrain Differentially Modulates Investigation of Opposite versus Same-Sex Urinary Chemosignals and Stimulates Mating in Male Mice.

前脑辅助嗅球输入的光遗传学激活差异调节异性与同性尿液化学信号的研究并刺激雄性小鼠的交配。

• DOI: 10.1523/eneuro.0010-17.2017
• 发表时间: 2017
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Kunkhyen,Tenzin;McCarthy,ElizabethA;Korzan,WayneJ;Doctor,Danielle;Han,Xue;Baum,MichaelJ;Cherry,JamesA
• 通讯作者: Cherry,JamesA

A comparison of the effects of male pheromone priming and optogenetic inhibition of accessory olfactory bulb forebrain inputs on the sexual behavior of estrous female mice.

• DOI: 10.1016/j.yhbeh.2016.12.011
• 发表时间: 2017-03
• 期刊: Hormones and behavior
• 影响因子: 3.5
• 作者: McCarthy EA;Kunkhyen T;Korzan WJ;Naik A;Maqsudlu A;Cherry JA;Baum MJ
• 通讯作者: Baum MJ

Either main or accessory olfactory system signaling can mediate the rewarding effects of estrous female chemosignals in sexually naive male mice.

• DOI: 10.1037/a0033945
• 发表时间: 2013-10
• 期刊: BEHAVIORAL NEUROSCIENCE
• 影响因子: 1.9
• 作者: Korzan, Wayne J.;Freamat, Mihael;Johnson, Adam G.;Cherry, James A.;Baum, Michael J.
• 通讯作者: Baum, Michael J.