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?

对后代的母性护理需要快速的神经行为变化，包括专门电路内的可塑性 处理婴儿信号（例如哭泣）对于神经可塑性很重要。 肽激素催产素的释放从下丘脑释放，对于 分娩和哺乳期，催产素也会作用于大脑，据信它可以增加社会的显着性。 信息，增强夫妻关系和母亲行为。临床研究表明催产素是一种很有前途的药物。 代理，患者有时能够更成功地参与社交互动。 虐待和忽视儿童的比率，但教家长发现和忽视儿童的培训计划和干预措施 对社会信号的反应已经取得了一些成功，这些疗法将受益于理解。 婴儿社交线索、催产素调节和与母亲行为相关的神经可塑性之间的相互作用。 在本提案中，我们将研究催产素对神经回路、可塑性和行为的影响。 我们研究了小鼠对婴儿超声波发声的神经行为反应。 母亲的照顾者，这需要与幼崽相处的经验，并由催产素促进。 基于听觉的母性行为序列首先由与母亲共同居住的幼崽雌性表达 中心假设是与母鼠或幼崽的社会接触会释放催产素，与幼崽互动。 我们将使用体内记录和成像，并结合行为来诱导听觉皮层的可塑性。 和光遗传学，以我们过去的工作为基础，研究皮质如何被催产素和幼崽叫声改变 在目标 1 中，我们测量共同居住期间听觉皮层的活动，并将其与皮质可塑性和调节相关。 在目标 2 中，我们研究了催产素如何调节兴奋性和抑制性。 最后，在目标 3 中，我们询问催产素如何合适。 婴儿暗示释放，启动这些听觉皮层变化并塑造新的母亲行为 母鼠。 综上所述，这里我们将使用行为实验结合光遗传学和体内记录 询问催产素如何释放并影响听觉皮层，使母亲能够识别婴儿的求救信号。 这些实验将提供有关神经回路和功能的基本且迫切需要的数据。 在一个长期存在的深刻问题的背景下，催产素信号在哺乳动物大脑中的后果 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？