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

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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.