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"Disruption of neuronal circuitry and the memory engram in young adult mice following neonatal hypoxic-ischemic injury:

“新生小鼠缺氧缺血性损伤后神经元回路和记忆印迹的破坏：

基本信息

批准号：
9892038
负责人：
Jennifer Christine Burnsed
金额：
$ 19.31万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
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/9892038
关键词：
3-Dimensional Affect Animal Model Area Behavior Behavioral Behavioral Mechanisms Brain Brain Hypoxia-Ischemia Cerebral Palsy Cessation of life Child Childhood Chronic Cognition Cognitive Cognitive deficits Computer software Data Developed Countries Development Electroencephalography Epilepsy Exhibits Exposure to Genetic Genetic Recombination Hippocampus (Brain)Hypoxia Hypoxic-Ischemic Brain Injury Image Infant Injury Intellectual functioning disability Intervention Ipsilateral Knowledge Lead Learning Lesion Light Link Lipids Magnetic Resonance Imaging Maps Measures Memory Memory impairment Methods Microscopy Modeling Morbidity - disease rate Mus Neonatal Neurologic Neurologic Examination Neurons Newborn Animals Newborn Infant Play Population Recurrence Research Personnel Resolution Retrieval Risk Rodent Model Role Seizures Short-Term Memory Structure Techniques Testing Transgenic Mice Work base behavioral outcome granule cell hypoxia neonatorum imaging study improved improved outcome individualized medicine infant outcome injured ischemic injury learned behavior mortality mouse model neonatal human neonatal hypoxic-ischemic brain injury neonatal period neonate neuronal circuitry novel postnatal prognostic tool skills spatial memory theories tissue processing young adult

项目摘要

PROJECT SUMMARY Cognitive and behavioral outcomes following neonatal hypoxic-ischemic encephalopathy (HIE) are difficult to predict during the neonatal period. Previous work has established that MRI and neurologic exam in the neonatal period are poor prognostic tools for behavioral and cognitive deficits. Deficits in working and spatial memory exist in young adult mice that were exposed to neonatal hypoxia-ischemia. Examining a well-established neonatal mouse model of hypoxic-ischemic brain injury using novel methods, our preliminary data has found that a subset of young adult mice exhibit interictal spikes and chronic abnormal neuronal activation in the hippocampal-parahippocampal circuit. The concept of a memory engram involves this circuit and that a specific memory is encoded is stored in a specific population of neurons. Therefore, we propose that the memory engram is disrupted by interictal spikes and chronically abnormal neuronal activity in the hippocampal-parahippocampal circuit related to neonatal HIE. First, we will characterize electrographic abnormalities and neuronal activity in the hippocampal circuitry in young adult mice following neonatal hypoxia-ischemia using neuronal activation mapping in lipid cleared transgenic mouse brains and high quality electrographic recordings. We will investigate the link between electrographic abnormalities, abnormal neuronal activity in hippocampal circuitry and disruption of the memory engram in this model.

项目总结