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: 10449282
• 负责人: Marcelo Dietrich
• 金额: $ 60.05万
• 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/10449282
• 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.

项目概要 发声（即哭泣）是新生儿生命中第一个也是最强烈的行为表现。新生儿 当与主要照顾者隔离时发出声音，吸引他们的注意力以接受安慰、照顾和帮助 营养。在人类中，非典型哭泣行为是神经发育障碍的症状，例如自闭症 和天使综合症。然而，不成熟的新生儿大脑如何控制声音行为是一个令人着迷的问题。 发育神经生物学中尚未解决的问题。该提案的目标是阐明神经网络 瞬时调节新生哺乳动物发声的电路。下丘脑是一个 根据使用的实验表明，哺乳动物大脑底部的区域可以介导发声 电刺激该大脑区域。在下丘脑中，有一个区域称为弓状核，它负责 包含两个神经元群，可产生刺豚鼠相关肽 (Agrp) 或阿片黑皮素原 （POMC）。我们的初步实验表明这两个神经元群体在 新生儿发声的发射。因此，在本提案中，我们将在电路中使用最先进的方法 将神经科学应用于新生儿大脑，以研究控制神经元的机制细节 Agrp 和 POMC 神经元的新生儿发声行为。最后，该项目将揭示新的神经元 控制发育中的哺乳动物大脑中精确行为输出的电路。该项目还将棚 关于产后早期声音行为如何动态变化的新见解。除了照明之外 生命早期行为控制的基本原则，该项目揭示的机械见解可能 还有助于了解几种神经发育疾病中声音行为受损的情况。