Dissecting the modulatory function of hypothalamic neurons in the temporarily restricted emission of vocalizations by neonatal mice

剖析下丘脑神经元在新生小鼠发声暂时受限中的调节功能

• 批准号: 10267760
• 负责人: Marcelo Dietrich
• 金额: $ 60.84万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267760
• 关键词: ART protein; Age; Angelman Syndrome; Architecture; Attention; Automobile Driving; Axon; Behavior; Behavior Control; Brain; Brain Mapping; Brain region; Calcium; Caregivers; Caring; Cells; Cessation of life; Coupled; Development; Disease; Electrical Stimulation of the Brain; Goals; Health behavior; Human; Hypothalamic structure; Impairment; Laboratories; Lead; Life; Light; Mammals; Mediating; Monitor; Motivation; Mus; Neonatal; Neurobiology; Neurodevelopmental Disorder; Neurons; Neurosciences; Opioid; Output; Peptides; Population; Presynaptic Terminals; Pro-Opiomelanocortin; Role; Signal Transduction; Software Tools; Specific qualifier value; Structure of nucleus infundibularis hypothalami; Testing; Transgenic Mice; Weaning; autism spectrum disorder; base; behavioral response; beta-Endorphin; developmental neurobiology; experimental study; fascinate; in vivo; insight; loss of function; mouse development; mu opioid receptors; neglect; neonatal brain; neonatal mice; neonate; neural circuit; neurobiological mechanism; neuronal circuitry; novel; nutrition; offspring; optogenetics; postnatal; postnatal development; postnatal period; primary caregiver; response; social; tool; vocal control; vocalization

PROJECT SUMMARY Vocalization (i.e., cry) is the first and most intense behavior manifestation in the life of a neonate. Neonates vocalize when isolated from their primary caregivers, attracting their attention to receive comfort, care, and nutrition. In humans, atypical cry behavior is symptomatic of neurodevelopmental disorders, such as autism and Angelman syndrome. However, how the immature neonatal brain controls vocal behavior is a fascinating question in developmental neurobiology that remains unsolved. The goal of this proposal is to elucidate neural circuits that transiently modulate the emission of vocalizations in neonatal mammals. The hypothalamus is a region in the bottom of the mammalian brain suggested to mediate vocalization based on experiments using electric stimulation of this brain region. In the hypothalamus, there is a region called the arcuate nucleus, which contains two populations of neurons that produce either Agouti-related peptide (Agrp) or Proopiomelanocortin (POMC). Our preliminary experiments suggest these two populations of neurons exert a modulatory role in the emission of neonatal vocalizations. Thus, in this proposal, we will use state-of-the-art approaches in circuit neurosciences applied to the neonatal brain to investigate the mechanistic details involved in the control of neonatal vocal behavior by Agrp and POMC neurons. At its conclusion, this project will reveal novel neuronal circuits that control precise behavior outputs in the developing mammalian brain. This project will also shed new light on how vocal behavior dynamically changes during early postnatal life. In addition to illuminating fundamental principles of behavior control early in life, the mechanistic insights revealed in this project might also aid the understanding of impaired vocal behavior in several neurodevelopmental diseases.

项目总结 发声(即哭声)是新生儿生活中第一个也是最强烈的行为表现。新生儿 在与主要照顾者隔绝时发声，吸引他们的注意力，以获得舒适、关怀和 营养。在人类中，非典型的哭闹行为是神经发育障碍的症状，如自闭症。 和安吉尔曼综合症。然而，未成熟的新生儿大脑如何控制发声行为是一个令人着迷的问题 发育神经生物学中仍未解决的问题。这项提议的目的是阐明神经细胞 暂时性调节新生哺乳动物发声的回路。下丘脑是一种 哺乳动物大脑底部的区域提示，根据实验，使用 电刺激对这一大脑区域的电刺激在下丘脑中，有一个叫做弓状核的区域，它 包含两组神经元，它们产生Agti相关肽(AgRP)或前阿片黑素皮质素 (POMC)。我们的初步实验表明，这两类神经元在 新生儿发声。因此，在这项提案中，我们将在巡回比赛中使用最先进的方法 神经科学应用于新生儿大脑，以研究参与控制的机制细节 AgRP和POMC神经元对新生儿发声行为的影响最后，这个项目将揭示新的神经元 在发育中的哺乳动物大脑中控制精确行为输出的电路。这一项目也将摆脱 发声行为如何在出生后早期发生动态变化的新视角。除了照亮外 早期行为控制的基本原则，这个项目中揭示的机械洞察力可能 也有助于理解几种神经发育疾病中受损的发声行为。