Neural Circuitry and Plasticity for Maternal Behavior

母亲行为的神经回路和可塑性

• 批准号: 9308448
• 负责人: Robert Crooks Froemke
• 金额: $ 40.3万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308448
• 关键词: Affect; Animals; Antibodies; Area; Auditory; Auditory area; Axon; Behavior; Behavioral; Biological; Brain; Caregivers; Caring; Cells; Child; Child Abuse and Neglect; Child Development; Child Rearing; Childbirth; Clinical Research; Crying; Cues; Data; Distress; Educational Intervention; Electrophysiology (science); Female; Goals; Home environment; Hormones; Housing; Human; Hypothalamic structure; Image; Infant; Infant Care; Lactation; Left; Libraries; Maternal Behavior; Measures; Mothers; Mus; Neuronal Plasticity; Neurons; Neurosciences; Neurosecretory Systems; Oxytocin; Oxytocin Receptor; Pair Bond; Parent-Child Relations; Parents; Patients; Peptides; Pharmacology Study; Physiological; Postpartum Depression; Postpartum Period; Psyche structure; Retrieval; Sensory; Shapes; Signal Transduction; Social Behavior; Social Interaction; Stimulus; Synapses; Synaptic plasticity; System; Testing; Therapeutic; Therapeutic Agents; Training Programs; Ultrasonics; Whole-Cell Recordings; Work; auditory processing; autism spectrum disorder; awake; base; behavioral response; behavioral study; child neglect; experience; experimental study; improved; in vivo; information processing; neglect; neural circuit; neurobehavioral; neuroregulation; offspring; optogenetics; paraventricular nucleus; peptide hormone; pup; receptor; relating to nervous system; response; sensory input; social; social anxiety; social cognition; sound; success; treatment strategy; two-photon; vocalization

Maternal care of offspring requires rapid neurobehavioral changes, including plasticity within circuits specialized for processing infant cues such as crying. Neuroendocrine signals are important for neuroplasticity, including release of the peptide hormone oxytocin. Oxytocin is released from the hypothalamus and is important for childbirth and lactation. Oxytocin also acts in the brain where it is believed to increase the salience of social information, enhancing pair bonding and maternal behavior. Clinical studies suggest that oxytocin is a promising therapeutic agent, with patients sometimes engaging more successfully in social interactions. There is a high rate of child maltreatment and neglect, but training programs and interventions that teach parents to detect and respond to social signals have had some success. These therapies would benefit from understanding the interactions between infant social cues, oxytocin modulation, and neuroplasticity relevant for maternal behaviors. In this proposal, we will study the neural circuitry, plasticity, and behavioral effects of oxytocin in the context of maternal behavior in mice. We study neurobehavioral responses to infant ultrasonic vocalizations by maternal caregivers, which requires experience with pups and is facilitated by oxytocin. We will study the sequence of auditory-based maternal behaviors first expressed by pup-naïve females co-housed with mothers and pups. The central hypothesis is that social contact with dam or pups releases oxytocin, interacting with pup calls to induce plasticity in auditory cortex. We will use in vivo recording and imaging, combined with behavior and optogenetics to examine how cortex is modified by oxytocin and pup call sounds, building on our past work on cortical plasticity and modulation. In Aim 1 we measure activity in auditory cortex during co-housing, relating retrieval behavior to cortical plasticity. In Aim 2, we examine the how oxytocin modulates excitatory and inhibitory cells and synapses for processing auditory social signals. Finally in Aim 3 we ask how oxytocin is appropriately released by infant cues, to initiate these auditory cortical changes and shape maternal behavior in newly- maternal mice. In summary, here we will use behavioral experiments combined with optogenetics and in vivo recordings to ask how oxytocin is released and affects auditory cortex, to enable maternal recognition of infant distress calls. These experiments will provide fundamental and urgently-needed data on the neural circuitry and functional consequences of oxytocin signaling in the mammalian brain, in the context of a deep and long-standing question in neuroscience: how are specific neural circuits specialized for sensory processing and maternal behavior?

母亲照顾后代需要迅速的神经行为变化，包括专门回路内的可塑性 来处理婴儿的线索比如哭泣神经内分泌信号对神经可塑性很重要，包括 释放缩氨酸荷尔蒙催产素。催产素是从下丘脑释放出来的， 分娩和哺乳。催产素也在大脑中起作用，据信它可以增加社交活动的显著性。 信息，增强配对和母性行为。临床研究表明催产素是一种很有前途的 治疗剂，患者有时会更成功地参与社交互动。存在高 虐待和忽视儿童的比率，但培训方案和干预措施，教父母发现和 对社交信号的反应已经取得了一些成功。这些疗法将受益于了解 婴儿的社会线索，催产素调制和神经可塑性之间的相互作用与母亲的行为。 在这个建议中，我们将研究催产素在大脑中的神经回路、可塑性和行为效应。 小鼠的母性行为。我们研究了婴儿超声波发声的神经行为反应， 产妇护理人员，这需要有照顾幼崽的经验，并通过催产素来促进。我们会研究 一系列基于行为的母性行为首先由与母亲共同居住的幼鼠首次表达 和小狗核心假设是，与母鼠或幼鼠的社会接触会释放催产素，与幼鼠相互作用。 来诱导听觉皮层的可塑性。我们将使用活体记录和成像，结合行为 和光遗传学来研究大脑皮层是如何被催产素和幼崽的叫声所改变的， 大脑皮层的可塑性和调节在目标1中，我们测量了共同居住期间听觉皮层的活动， 提取行为与皮层可塑性的关系。在目标2中，我们研究了催产素如何调节兴奋性和抑制性 处理听觉社交信号的细胞和突触。最后，在目标3中，我们问催产素如何适当地 婴儿的暗示释放，启动这些听觉皮层的变化，并塑造母亲的行为在新的- 母鼠 综上所述，在这里我们将使用行为实验结合光遗传学和体内记录 研究催产素是如何释放并影响听觉皮层的，从而使母亲能够识别婴儿的求救信号。 这些实验将提供基本的和迫切需要的数据的神经电路和功能 哺乳动物大脑中催产素信号的后果，在一个深刻而长期的问题的背景下， 神经科学：特定的神经回路如何专门用于感觉处理和母性行为？