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Investigating perineuronal nets and hippocampal plasticity in early life adversity-induced anxiety

研究早期生活逆境引起的焦虑中的神经周围网和海马可塑性

基本信息

批准号：
9923465
负责人：
Elizabeth Gould
金额：
$ 40.5万
依托单位：
PRINCETON 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：
2018-08-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9923465
关键词：
Address Adult Adverse event Anterior Anxiety Anxiety Disorders Behavior Brain Cell physiology Cells Chemicals Cholecystokinin Confocal Microscopy Data Development Electroencephalography Electron Microscopy Electrophysiology (science)Extracellular Matrix Feedback Female Frequencies Goals Hippocampus (Brain)Human Incidence Individual Differences Interneurons Label Lead Light Link Mental Health Moods Mus Myoepithelial cell Neurons Outcome Parvalbumins Pattern Play Process Psychopathology Regulation Reporting Risk Factors Rodent Role Stress Structure Synapses Testing Transgenic Organisms Treatment Efficacy abuse neglect adult neurogenesis anxiety-like behavior anxious anxious behavior critical period dentate gyrus design early life adversity early life stress excessive anxiety experimental study granule cell in vivo male mouse model nerve supply neuroimaging neuropsychiatric disorder neuropsychiatry novel therapeutics pediatric trauma postnatal prevent retroviral-mediated

项目摘要

PROJECT SUMMARY Early life adversity is associated with an increased incidence of anxiety disorders in adulthood. Understanding the cellular processes that connect early life stress with excessive anxiety may provide clues for the development of new therapies to treat anxiety disorders. Studies in humans and rodents have identified subregions of the hippocampus as important for anxiety regulation. Neuronal oscillations in both theta and gamma frequency ranges in the hippocampus have been linked to anxious behavior and these oscillations are driven by coordinated activity among a specific class of inhibitory interneurons, the parvalbumin positive (PV+) basket cells. Perineuronal nets (PNNs), extracellular matrix structures that modulate plasticity and have been linked to psychopathology, surround many PV+ basket cells. In mice, early life adversity increases PNN formation around PV+ cells in the ventral hippocampus, raising the possibility that this change leads to early life adversity-induced enhancement of neuronal oscillations and anxiety. Adult neurogenesis in the ventral hippocampus is also impacted by early adverse experience and adult-generated granule cells are known to synapse with PV+ basket cells. The possibility that connections between adult-generated neurons and inhibitory interneurons are altered by postnatal stress, potentially through alterations in PNNs, and thus produce enhanced neuronal oscillations and anxiety remains unknown. This proposal is designed to address the gaps in our understanding about how early life stress alters hippocampal PNNs, adult-generated granule cell connections with inhibitory interneurons, neuronal oscillations and anxiety and to explore the connections among these effects. The proposed experiments will use a mouse model of early life stress, manipulations of PNNs in the hippocampus, retroviral labeling of new granule cells in the hippocampus, immunolabeling combined with confocal microscopy and electron microscopy, transgenic and retroviral-mediated manipulation of adult-generated neuron number, in vivo electrophysiology during behavior and anxiety test analyses in adult male and female mice. The studies in this proposal are designed to achieve three significant and related, but not interdependent, aims regarding the influence of early life stress on hippocampal plasticity in adulthood with the long-term goal of understanding the cellular changes that lead to increased neuronal oscillations and anxiety.

项目总结