2000 — 2004 |
Coolen, Lique M |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Mechanism Mediatiing Male Behavior @ University of Cincinnati
The long-term goal of the current research is to understand the neural pathways and mechanisms underlying motivated behaviors, and specifically those that mediate the expression of male sexual behavior. Male sexual behavior is a complex behavior dependent on both intrinsic and external factors. While much research has focused on the role of olfactory or hormonal signals, much less is known about the influence of genitosensory or hormonal signals, much less is known about the influence of genitosensory cues in the control of male sexual behavior. The aim of the present proposal is to delineate the neural pathway by which genitosensory input related to population reaches motivation centers in the forebrain, and investigate the functional role of this pathway in male sexual behavior. Previous work from our laboratory has demonstrated the existence of a neural subcircuit in the forebrain that is specifically related to ejaculation in male rats. Our preliminary work has provided strong evidence for a candidate pathway that may relay ejaculation-specific genitosensory input to this subcircuit. This pathway includes a subset of neurons in the lumbar spinal cord that project to a specific thalamic nucleus, which in turn, projects to forebrain regions critical for sexual behavior. The current proposal will confirm the existence of this pathway and address three additional questions: (1) Which peripheral nerves and interneurons convey genitosensory information from the male reproductive organs to the lumbar spinal cord? (2) Does this pathway convey genitosensory stimuli associated specifically with ejaculation? (3) Is relay of this genitosensory information critical for the expression of male sexual behavior? These studies will shed light on an issue of long standing interest and fascination, namely the neurobiological basis of sexual pleasure. The proposed experiments, focusing on pathway conveying afferent genitosensory information, will fill a crucial gap in our understanding of the motivational circuitry mediating sexual behavior. Since neural mechanisms controlling ejaculation in humans are similar to that in the rat, results of these experiments will have relevance to our understanding of human sexual dysfunction and may contribute to the development of new therapeutic approaches.
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0.997 |
2002 — 2006 |
Coolen, Lique M |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Role of Endogenous Opioids in Male Reproductive Behavior @ University of Cincinnati
The goal of this research is to elucidate neural mechanisms by which endogenous opioid peptides coordinate male reproductive behavior. The effects of opiates and opioid peptides on masculine copulatory behavior have been discussed for centuries. Taken together, these studies lead to the hypothesis that endogenous opioid peptides are released during sexual behavior. However, to date, the site(s) of release and action of the endogenous peptides are still unclear. In addition it is unknown which aspect of the behavior causes the release of the peptides, as well as the precise identity of these opioid peptides. Moreover, the behavioral significance of the action of opioids is unclear. Therefore, the current proposal will address these questions. First we will establish a) when during sexual behavior, and b) at which sites opioids are acting during mating. The proposed experiments will investigate internalization of mu opioid receptors in order to understand site-specific changes accompanying the motivational and consummatory responses underlying sexual behavior. Excitingly, preliminary data from our laboratory has already demonstrated internalization of the mu opioid receptor in the male rat preoptic area of the hypothalamus following copulation. Furthermore, the question which endogenous opioid peptides are released during sexual behavior will be addressed using markers for neural activation and electron microscopy to visualize synaptic contacts between opioid peptide terminals and mu opioid receptor neurons. Finally, the behavioral significant of activation of opioid receptors induced by sexual behavior, will be tested using pharmacological manipulations of the receptor, and antisense application to reduce translation of receptor RNA. These studies will provide the first evidence, at a cellular level, for the localization of opioid peptide action during male sexual behavior. This will augment currently available pharmacological effects of opioids on sexual behavior, by providing data on the anatomical specificity of these effects. Moreover, the proposed research will advance our understanding of the involvement of endogenous opioid peptides in a naturally occurring motivated behavior. Since the pathways underlying natural motivated behaviors have striking overlaps with the circuitries involved in substance abuse, studying the role of endogenous opioids for natural motivation may therefore also reveal important information regarding the underlying mechanisms of substance abuse.
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0.997 |
2004 — 2007 |
Coolen, Lique M |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Regulation of Ejaculation @ University of Western Ontario
DESCRIPTION (provided by applicant): Male sexual behavior is a complex behavior consisting of several different components. The mechanisms underlying erectile and ejaculatory function has been subject of investigation in many species, including man. However, the central control of ejaculation remains poorly understood. It is well established that ejaculation is a reflex and the central components necessary to complete this reflex are located in the lumbosacral spinal cord. This spinal ejaculatory neural system is under descending influence from supraspinal centers. However, ejaculatory reflexes remain intact when supraspinal inputs are interrupted, suggesting the existence of a spinal ejaculation generator. Until recently, the precise anatomical location and neurochemical identity of neurons that comprise the ejaculation generator has been unknown. Recently, we provided evidence that a population of lumbar spinothalamic (LSt) neurons plays a pivotal role in generation of ejaculatory behavior, suggesting that these cells form a critical component of the ejaculation generator. Moreover, preliminary data indicates that LSt cells have additional characteristics consistent with their role as a component of an ejaculation generator. In particular, these cells receive sensory inputs related to the onset of ejaculation and in turn project to preganglionic sympathetic and parasympathetic neurons in the lumbosacral spinal cord that mediate components of ejaculation. Thus, LSt cells appear to be in the position to integrate and coordinate inputs during sexual activity and outputs needed to trigger ejaculation. These discoveries provide, for the first time, a rich target for investigating the neural organization of ejaculation. In the current proposal we propose multidisciplinary studies utilizing neuroanatomical, physiological, pharmacological, and behavioral techniques, to further investigate the mating related inputs to LSt cells (Specific Aim 1), the efferent outputs of LSt cells (Specific Aim 2), and the sources of supraspinal influence on LSt neurons (Specific Aim 3). These studies will provide further insight into the spinal mechanisms involved in control of the ejaculatory reflex. Detailed understanding of a spinal ejaculation generator will significantly benefit treatment of sexual dysfunction, in particular related to ejaculation. Moreover, these studies will provide novel insights into the mechanisms regulating coordination of sensory, autonomic, and motor systems in the spinal cord.
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0.997 |
2019 — 2021 |
Coolen, Lique M Steward, Oswald [⬀] |
R25Activity Code Description: For support to develop and/or implement a program as it relates to a category in one or more of the areas of education, information, training, technical assistance, coordination, or evaluation. |
Foundations of Rigorous Neuroscience Research @ Society For Neuroscience
Foundations of Rigorous Neuroscience Research Project Abstract Scientists at all career stages must be well-trained in the foundations of rigorous and reproducible research. Institutions and individual laboratories play a critical role in training researchers in aspects of rigorous laboratory practices, such as experimental design, data analysis, and reporting. However, systemic issues inherent to research culture often hinder scientists? abilities to apply these principles to their work. Factors collectively referred to as the sociology of science include biases that can influence experimentation and interpretation; practices related to data collection, management, and sharing; and incentives that underlie career advancement and the stability of scientists? research programs. The Society for Neuroscience (SfN) proposes to develop resources that focus on the sociology of science through the multimodal training series ? Foundations of Rigorous Neuroscience Research. The proposed program will build on SfN?s previous training efforts in scientific rigor and pursue two specific aims: (1) Develop multimodal platforms that promote awareness of barriers and solutions related to practicing rigorous and reproducible neuroscience research at all career stages. Through in- person workshops, a virtual conference, and online programming (videos, podcast series, case studies, written materials, and online discussions), training will focus on topics such as sources of bias that can influence scientific judgments, data sharing practices, and career advancement incentives. (2) Develop exportable training modules ? digital toolkits ? with quickly digestible, accessible resources to inform and empower researchers at all career stages to enhance rigor and reproducibility in their laboratory practices and professional activities. With content derived from programming under Specific Aim 1, SfN will produce and disseminate four digital ?toolkits? tailored to scientists in distinct career stages: graduate students, postdoctoral trainees, early-career independent investigators, and established investigators. Resources in each toolkit will include formats such as discussion guides, tip sheets, videos, brief downloadable PowerPoint presentations from experts, and ?citable statements? on best practices and opinions that users can deploy at their home institutions to influence opinion. With more than 1,000 disorders of the brain and nervous system resulting in more hospitalizations and lost productivity than any other disease group, it is critical to develop a diverse and well-trained neuroscience research workforce to find new and innovative ways to prevent and treat neurological illnesses. The research in which this workforce engages must be rigorous and reproducible, as other areas of science and scientific discovery will benefit from new discoveries. SfN seeks to develop resources that promote awareness of barriers and solutions related to conducting rigorous research, and to empower researchers at all levels to enhance rigor in their laboratory and professional practices.
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0.912 |