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

项目摘要 发声（即，哭）是新生儿生命中第一个也是最强烈的行为表现。新生儿 当与他们的主要照顾者隔离时发声，吸引他们的注意力以获得安慰，照顾， 营养在人类中，非典型的哭泣行为是神经发育障碍的症状，如自闭症 和安格尔曼综合征然而，不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。 这是发育神经生物学中尚未解决的问题。这项提案的目的是阐明神经 在新生哺乳动物中短暂调节发声的电路。下丘脑是一个 哺乳动物大脑底部的一个区域，根据使用 电刺激这个大脑区域。在下丘脑中，有一个叫做弓状核的区域， 包含两个神经元群体，产生Agouti相关肽（Agrp）或前阿黑皮素 （POMC）。我们的初步实验表明，这两个群体的神经元发挥调节作用，在 新生儿发声。因此，在本提案中，我们将在电路中使用最先进的方法 神经科学应用于新生儿大脑，以调查参与控制的机械细节。 Agrp和POMC神经元的发声行为。在其结论，该项目将揭示新的神经元 控制哺乳动物大脑发育中精确行为输出的回路。该项目还将 关于发声行为在出生后早期如何动态变化的新见解。除了启发 生命早期行为控制的基本原则，在这个项目中揭示的机械见解可能 也有助于理解几种神经发育疾病中受损的发声行为。

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.