Developmental Programming of Neural Circuits Impacting Hypothalamic Integration

影响下丘脑整合的神经回路的发育编程

• 批准号: 10617287
• 负责人: RICHARD B SIMERLY
• 金额: $ 51.24万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-03 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617287
• 关键词: Address; Adult; Affect; Architecture; Behavioral; Body Weight; Brain; Brain imaging; Brain region; Calcium; Cell Nucleus; Cerebral cortex; Cues; Data; Development; Endocrine; Environmental Risk Factor; Esthesia; Exposure to; Feeding behaviors; Health; High Fat Diet; Hormones; Hypothalamic structure; Image; Individual; Label; Lactation; Lateral; Leptin; Life; Light; Maternal Exposure; Mediating; Metabolic; Modification; Mus; Neural Pathways; Neurons; Neurophysiology - biologic function; Nucleus solitarius; Obesity; Output; Pathway interactions; Play; Population; Predisposition; Process; Property; Prosencephalon; Recommendation; Regulation; Role; Sensory; Signal Transduction; Stimulus; Structure; Structure of nucleus infundibularis hypothalami; System; Testing; Text; Tissues; Vagus nerve structure; Viral; awake; cell type; developmental neurobiology; energy balance; feeding; fluorescence imaging; in vivo; in vivo imaging; insight; metabolic phenotype; microendoscopy; mother nutrition; neural; neural circuit; neural network; neurobiological mechanism; nutrition; offspring; paraventricular nucleus; perinatal environment; postnatal; postsynaptic neurons; response; transmission process

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Environmental perturbations that occur during early postnatal life, such as exposure to maternal high fat diet during lactation (MHFD), may alter how interosensory signals are centrally processed and transmitted in adulthood, leading to dysregulation of feeding behavior. Although MHFD is known to alter feeding behavior in offspring, the underlying neurobiological mechanisms remain largely unexplored. The overarching premise for the proposed studies is that, MHFD exposure causes significant changes in the organization and activity of neural pathways conveying convergent interoceptive information to key components of neural circuits known to regulate feeding behavior. Because the architecture of neural pathways transmitting interosensory information is a state defining feature of how the brain integrates interoceptive sensation, understanding how MHFD impacts quantitative changes in the input/output structure and activity of these circuits will provide mechanistic insight into developmental programming of metabolic phenotype. Viscerosensory information is transmitted centrally by the vagus nerve to the nucleus of the solitary tract (NTS), which contains neurons known to convey regulatory signals to the hypothalamus, as well as to other brain regions involved in the control of feeding. Similarly, circulating levels of leptin signal the state of systemic energy stores and regulate neurons in multiple brain regions. The arcuate nucleus of the hypothalamus (ARH) contains AgRP neurons, which play a key role in the regulation of feeding and distribute leptin and other metabolic signals to downstream components of feeding circuitry, such as the paraventricular hypothalamic nucleus (PVH). In contrast, the lateral hypothalamus (LHA) shares strong connections with cerebral cortex and plays a key role in consummatory aspects of feeding. For the proposed studies, tissue clearing and light sheet fluorescence imaging will be used to label, image and register the brain-wide distributions of neurons that provide inputs to the ARH, PVH and LHA in order to test the hypothesis that MHFD exposure causes permanent changes in the multiregional convergence of projections to distinct components of feeding circuitry. (Specific Aim 1). Calcium-based microendoscopy will be used to determine how MHFD impacts the ensemble activity of neurons in the PVH, and LHA, within the context of feeding behavior (Specific Aim 2). Together, the studies proposed in this 3-year project will identify neural substrates that integrate diverse metabolic signals required for coordinated control of feeding behavior, as well as contribute to our understanding of the developmental neurobiology of metabolic programming.

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项目成果

A critical period for the trophic actions of leptin on AgRP neurons in the arcuate nucleus of the hypothalamus.

• DOI: 10.1002/cne.24327
• 发表时间: 2018-01-01
• 期刊: The Journal of comparative neurology
• 作者: Kamitakahara A;Bouyer K;Wang CH;Simerly R
• 通讯作者: Simerly R

Organization of neural systems expressing melanocortin-3 receptors in the mouse brain: Evidence for sexual dimorphism.

在小鼠大脑中表达黑素皮质3受体的神经系统的组织：性二态性的证据。

• DOI: 10.1002/cne.25379
• 发表时间: 2022-11
• 期刊: JOURNAL OF COMPARATIVE NEUROLOGY
• 影响因子: 2.5
• 作者: Bedenbaugh, Michelle N.;Brener, Samantha C.;Maldonado, Jose;Lippert, Rachel N.;Sweeney, Patrick;Cone, Roger D.;Simerly, Richard B.
• 通讯作者: Simerly, Richard B.

Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus.

• DOI: 10.7554/elife.59857
• 发表时间: 2020-11-18
• 期刊: eLife
• 影响因子: 7.7
• 作者: Biddinger JE;Lazarenko RM;Scott MM;Simerly R
• 通讯作者: Simerly R