Neural mechanisms of infant attachment

婴儿依恋的神经机制

基本信息

批准号：
10307129
负责人：
Elizabeth A.D. Hammock
金额：
$ 37.58万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10307129
关键词：
Acute Address Adult Affect Afferent Neurons Anatomy Autoradiography Behavior Behavioral Binding Birth Brain Caregivers Clinical Cre-LoxP Data Development Dose Face Female Fiber Foundations Frequencies Future Ganglia Goals Harvest Health Human Milk In Situ Hybridization Individual Differences Infant Infant Behavior Infant Development Knowledge Ligand Binding Link Liquid substance Long-Term Effects Mental Health Mental disorders Messenger RNA Milk Ejection Molecular Mothers Mus Neuroanatomy Neurons Newborn Infant Nociceptors OXT gene Oral Outcome Oxytocin Oxytocin Receptor Peptides Perinatal Peripheral Play Process Production Quality of life Reflex action Research Research Project Grants Risk Role Saliva Sensory Sensory Ganglia Sex Differences Signal Transduction Social Behavior Social Development Social Environment Source Stimulus Structure of trigeminal ganglion Subcellular Anatomy System Testing Trigeminal System Work behavior test brain behavior experimental study immunoreactivity improved insight intergenerational lifetime risk male neonatal mice neonatal period neonate neurobehavioral neuromechanism neuronal cell body novel postnatal preventive intervention receptor relating to nervous system response sensory mechanism social social contact social influence trafficking transmission process

项目摘要

Infant attachment to a caregiver is required for the typical development of social behavior and reduces the lifetime risk for mental illness. The underlying molecular and neural mechanisms of infant attachment to a caregiver are not well-characterized. Oxytocin (OXT) plays an important role in adult social behavior and has been hypothesized to play a role in infant attachment. This proposal will test a specific modulatory role for OXT acting at peripheral OXT receptors (OXTR) in infant attachment-related brain and behavior development. We have recently identified OXTR in the periphery of infant mice, including the face and oronasal cavity. Given the presence of OXT in maternal fluids such as saliva and breast milk, this suggests a simple hypothesis that maternal OXT could bind to infant peripheral OXTR to bias brain and behavioral development toward the social environment. In this proposal, we will determine the brain and behavioral effects of OXT acting upon peripheral OXTR in infant mice. First, we will perform anatomical studies to define the relevant circuitry from the periphery to the brain. Second, we will determine if these peripheral OXTR play a role in social orienting and contact behavior in neonates. Finally, we will determine if these peripheral OXTR influence the development of a key player in later social behavior- the infant’s own OXT production. Individual differences in the levels of OXT contribute to individual differences in social behavior and mental health. However, we know very little about how these individual differences in OXT are influenced by social contact in development or how social stimuli elicit OXT activity the socially naïve infant brain. This proposal will help address these knowledge gaps. Using infant mice, the long-term goals of this project are to understand 1) how social contact is transduced into the infant brain, 2) how the socially naïve neonate responds to exogenous OXT at the level of brain and behavior in the neonatal period, and 3) how social contact influences individual differences in OXT levels in the neonate. In addition, by performing these studies in male and female infant mice, we will ascertain potential sex differences in the acute response to social contact and OXT in the neonatal period. Further, because these experiments will clarify the roles of OXTR in the oronasal cavity, the findings may have broader applicability for understanding the mechanism of action of intranasal delivery of clinical doses of OXT. These experiments will determine the mechanisms of acute change in the neonate, with the potential for future experiments to determine the mechanisms of the long term effects of these changes.

婴儿对照顾者的依恋是典型的社会行为发展所必需的，并且可以降低婴儿一生患精神疾病的风险。催产素（OXT）在婴儿依恋的潜在分子和神经机制中发挥着重要作用。该提案将测试 OXT 在婴儿依恋相关大脑和行为发育中作用于外周 OXT 受体 (OXTR) 的特定调节作用。周边鉴于母体液体（例如唾液和母乳）中存在 OXT，这表明母体 OXT 可以与婴儿外周 OXTR 结合，从而使大脑和行为发育偏向于社会环境。在本提案中，我们将确定 OXT 对婴儿小鼠外周 OXTR 的大脑和行为影响。首先，我们将进行解剖学研究，以确定从外周到大脑的相关电路。其次，我们将确定这些外周是否存在。最后，我们将确定这些外周 OXTR 是否会影响后期社会行为的关键因素——婴儿自身 OXT 产生的个体差异。然而，我们对 OXT 的个体差异如何受到发育过程中的社会接触的影响以及社会刺激如何引发 OXT 活动的了解知之甚少。该提案将有助于解决这些知识差距。使用婴儿小鼠，该项目的长期目标是了解 1) 社会接触如何传导到婴儿大脑中，2) 不懂社交的新生儿在新生儿期如何在大脑和行为水平上对外源性 OXT 做出反应，以及 3 ）社会接触如何影响新生儿 OXT 水平的个体差异此外，通过对雄性和雌性婴儿小鼠进行这些研究，我们将确定新生儿时期对社会接触和 OXT 的急性反应的潜在性别差异。由于这些实验将阐明 OXTR 在口鼻腔中的作用，因此这些发现可能对理解临床剂量的 OXT 鼻内递送的作用机制具有更广泛的适用性。未来的实验有可能确定这些变化的长期影响的机制。