Olfactory Circuits for Reproduction and Reward

用于繁殖和奖励的嗅觉回路

基本信息

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
项目类别：
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

项目摘要

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.

在人类接触体气味剂中，可以产生特定性别的神经内分泌反应，允许基于主要组织相容性等位基因的差异和性别依赖性激活的气味歧视下丘脑的区域涉及繁殖。但是，未能通过这些信号访问生殖电路阻碍了我们对人类“信息素”如何可能的理解影响行为。此外，尽管有证据表明这种生物学相关的气味可能是自然的奖励，将气味传达到中介多巴胺系统中的气味的路线加固尚未确定。使用小鼠，我们已经确定了主嗅球的直接投影（MOB）到中间杏仁核（ME），该杏仁核（ME）投射到控制繁殖的下丘脑的区域。在人类中保存这一途径可以解释气味如何影响性伴侣的偏好和交配行为。由于小鼠中的主要和辅助嗅觉系统都可以检测到化学信号，因此我们将比较每个系统在调节控制性的嗅觉线索的响应中的参与动力和回报。首先，我们将确定从腹群到Me的直接途径是在两个性别中被男性和女性尿路挥发物差异激活，成年人是否暴露睾丸激素调节此类反应的强度。接下来，我们将确定嗅觉的子集是否表达TRP阳离子通道项目的M5亚型的感觉神经元将由我支配二尖瓣细胞并有选择地响应异性尿挥发物。因为我们已经观察到，许多腹暴徒的投影向ME投影也将分支发送到嗅觉皮层，我们将绘制这些投影的目标，以确定嗅觉皮层中的特定位点是否优先男性和女性支配和不同。 Choi等人（2005年）提出生殖意义的气味小鼠在ME和床核中激活表达转录因子LHX6的神经元电路末端（BNST），然后在腹侧下丘脑核（VMH）中终止。我们将确定在LHX6-中，主要与附属嗅觉输入选择性诱导FOS（神经元活性的标记）的程度在雄性小鼠的ME，BNST和VMH中表达神经元，并确定这些神经元是否发送轴突到腹侧对段区域，中溶液系统的多巴胺能细胞体的位置。最后，我们会的使用条件的地方偏好范式比较由雄性小鼠的主要辅助系统。我们的结果应提供对嗅觉和边缘电路的见解该过程繁殖明显的气味提示，也可能有助于阐明非富特性的机制（视觉，听觉或纯认知）输入控制人类的性伴侣偏好和性唤醒。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
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.