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.

 描述（申请人提供）：禁食后，在重新引入食物后两小时内观察到饱腹感，并伴有大脑不同区域的神经元激活，包括下丘脑室旁核和背内侧核、臂旁核、孤束核（NTS）的内侧和连合亚部，杏仁核中央核（CeA）和终纹床核（BNST），它们都通过影响大脑中的自主神经和奖励中心而与食物摄入的调节相关。除了这些区域，我们在初步研究中观察到丘脑旁核（PSTN）中的cfos激活，这是一个特征不明显的脑核，我们假设它包括饱腹感回路中的一个主要节点。为了验证这一假设，我们将阐明如何refeeding-activated PSTN神经元整合到中枢神经系统使用经典的神经解剖追踪技术（逆行和顺行），并测试这些神经元的功能，在调节食欲，使用DREADD激活或抑制PSTN活动。解剖图将被构建的再喂养激活的PSTN神经元的投射途径，包括在PSTN中的神经元的拓扑结构，投射到已知的食欲调节中心，以及激活的神经元是否有一个单一的，专用的投影场或多个投影场。将通过使用表达与mCherry融合的DREADD的AAV激活或抑制PSTN神经元胞体来测试该回路的功能性，所述mCherry双侧注射到PSTN中，所述mCherry响应于氯氮平-N-氧化物（CNO）的全身施用表达hM 3Dq以激活PSTN神经元或表达hM 4Di以沉默PSTN神经元。使用的行为读数将包括测量食物和水的摄入量和运动活动的自动笼使用禁食再喂养的范例，并通过操作性条件反射研究奖励喂养。我们认为，这些研究将导致对食欲如何被抑制的新见解，并更好地了解食物摄入调节的潜在机制。

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