Role of the Parasubthalamic Nucleus (PSTN) in Appetite Regulation

副丘脑核 (PSTN) 在食欲调节中的作用

• 批准号: 9242683
• 负责人: RONALD Michael LECHAN
• 金额: $ 20.63万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-14 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9242683
• 关键词: Adult; Adverse effects; Affect; Amygdaloid structure; Anatomy; Animals; Anorexia Nervosa; Appetite Disorder; Appetite Regulation; Area; Behavioral; Bilateral; Brain; Cardiovascular system; Cell Nucleus; Child; Clozapine; Desire for food; Development; Dyslipidemias; Eating; Employee Strikes; Fasting; Food; Food Intake Regulation; Glucose Intolerance; Goals; Grant; Health; Homeostasis; Hour; Hypertension; Injectable; Laboratories; Left; Life Style; Location; Maps; Measurable; Measures; Medial; Medial Dorsal Nucleus; Metabolic; Molecular; Morbidity - disease rate; Motor Activity; Neuraxis; Neurobiology; Neurons; Obesity; Operant Conditioning; Output; Oxides; Pathway interactions; Public Health; Regulation; Research; Rewards; Risk; Role; Satiation; Structure of nucleus infundibularis hypothalami; Structure of terminal stria nuclei of preoptic region; Techniques; Testing; Water consumption; designer receptors exclusively activated by designer drugs; environmental change; feeding; hedonic; insight; nonalcoholic steatohepatitis; novel strategies; parabrachial nucleus; paraventricular nucleus; prevent; public health relevance; response

 DESCRIPTION (provided by applicant): Following fasting, satiety is observed within two hours after reintroducing food and accompanied by neuronal activation in distinct areas of the brain including the hypothalamic paraventricular nucleus and dorsomedial nucleus, parabrachial nucleus, medial and commissural subdivisions of the nucleus tractus solitarius (NTS), central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST) that have all been associated with the regulation of food intake by affecting autonomic and reward centers in the brain. In addition to these regions, we observed in our preliminary studies striking cfos activation in the parasubthalamic nucleus (PSTN), a poorly characterized nucleus in the brain that we hypothesize comprises a major node in the satiety circuitry. To test this hypothesis, we will elucidate how refeeding-activated PSTN neurons are integrated into the central nervous system using classic neuroanatomical tracing techniques (retrograde and anterograde), and to test the functionality of these neurons in the regulation of appetite, the use of DREADDs to activate or inhibit PSTN activity. Anatomical maps will be constructed of the projection pathways of refeeding-activated PSTN neurons including the topography of neurons in the PSTN that project to known appetite regulating centers and whether activated neurons have a single, dedicated projection field or multiple projection fields. The functionality of this circuitry will e tested by activating or inhibiting PSTN neuronal perikarya using AAV expressing DREADDs fused to mCherry injected bilaterally into the PSTN that either expresses hM3Dq to activate PSTN neurons or hM4Di to silence PSTN neurons in response to the systemic administration of clozapine-N-oxide (CNO). Behavioral readouts used will include measuring food and water intake and locomotor activity in automated cages using a fasting-refeeding paradigm, and by operant conditioning to study reward feeding. We propose that these studies will lead to new insights about how appetite is suppressed and better understanding about the mechanisms underlying the regulation of food intake.

 DESCRIPTION (provided by applicable): Following fasting, satiety is observed within two hours after reintroducing food and accomplished by neuronal activation in distinct areas of the brain including the hypothalamic paraventricular nucleus and dorsomedial nucleus, parabrachial nucleus, media and commissural subdivisions of the nucleus tractus solidarius (NTS), central nucleus of the amygdala （BNST）（BNST）的（CEA）和床核通过影响大脑中的自主和奖励中心而与食物摄入的调节有关。除了这些区域外，我们在旁皮丘脑核us（PSTN）中引人注目的CFO激活的初步研究中观察到，大脑中的核核核素的特征较差，我们假设我们假设缎带中的主要节点。为了检验这一假设，我们将阐明如何使用经典的神经解剖学跟踪技术（逆行和顺序）将引用激活的PSTN神经元集成到中枢神经系统系统中，并测试这些神经元在食欲调节中的功能，使用deadds的使用，用于激活或抑制PSTN活性。解剖图将由引用激活的PSTN神经元的投影途径构建，包括PSTN中神经元的地形，该神经元在已知的食欲调节中心项目以及激活的神经元是否具有单个，专用的投影场或多个投影场。 The functionality of this circuitry will e tested by activating or inhibiting PSTN neuronal perikarya using AAV expressing DREADDs fused to mCherry injected bilaterally into the PSTN that either expresses hM3Dq to activate PSTN neurons or hM4Di to silence PSTN neurons in response to the systemic administration of clozapine-N-oxide (CNO).所使用的行为读数将包括使用禁食饲料范式在自动笼中测量食物和水的摄入量和运动活动，以及通过操作条件来研究奖励喂养。我们建议这些研究将导致有关如何抑制食欲的新见解，并更好地了解食物摄入调节的机制。

项目成果

Neuronal connections of the central amygdalar nucleus with refeeding-activated brain areas in rats.

大鼠中央杏仁核与再进食激活大脑区域的神经元连接。

• DOI: 10.1007/s00429-017-1501-4
• 发表时间: 2018
• 期刊: Brain structure & function
• 影响因子: 3.1
• 作者: Zséli,Györgyi;Vida,Barbara;Szilvásy-Szabó,Anett;Tóth,Mónika;Lechan,RonaldM;Fekete,Csaba
• 通讯作者: Fekete,Csaba