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    Amanda Hernan, PhD

    Research Scientist

    Nemours Children's Hospital, Delaware 1600 Rockland Road Wilmington, DE 19803

    Biography

    One in every 26 people will be diagnosed with epilepsy some time in their life, many of these diagnoses happen in children. We have found that seizures during the early life period are associated with significant impairments in learning and memory and attention deficits that persist to adulthood. These learning and memory impairments are the result of abnormal firing patterns in the brain in specific brain regions, such as the hippocampus and the prefrontal cortex. I have previously shown that ACTH, a hormone that is an endogenous part of the HPA axis, can prevent cognitive impairment in the context of early life seizures. I believe this is through a mechanism that involves ACTH acting as a neuropeptide on a specific set of receptors in the brain. My lab uses state-of-the-art single neuron recording techniques to examine how circuits control behavior and how abnormal neural processing can lead to cognitive impairment in neurodevelopmental diseases, such as pediatric epilepsy. Specific projects in my lab involve using in vivo single unit and local field potential recordings to record neural networks within and between the prefrontal cortex and the hippocampus simultaneously during tasks that require working memory and executive attention to: 1) examine the long-lasting effects of early life insults (like seizures) on specific neural network parameters that underlie cognition, and 2) test the protective role of early treatment with neuropeptide modulators (like the melanocortin peptides) on cognition and the underlying neural firing patterns. My lab is also interested in 3) the acute role these neuropeptides play in modulating developing neural networks. Many neuropeptide receptors, including those for the melanocortins, are located on both neurons and glia. We are interested in how glia and neurons interact dynamically during development, how this interaction can be affected by seizures, and how neuropeptide modulators can alter this interaction. My work is poised to challenge a particular dogma of pediatric epilepsy treatment, namely that treating seizures is the only effective way to prevent deleterious cognitive outcomes. The potential findings of this research, therefore, have huge implications for the way physicians treat epilepsy in children.

    Education

    • BS, BA - Case Western Reserve University, Biology, Psychology, 2007
    • PhD - Dartmouth College, Experimental and Molecular Medicine (Neuroscience), 2013

    • Attention
    • Cognition
    • Early Life Seizures
    • Epilepsy
    • Prefrontal Cortex

    • Network‐based analysis predicts interacting genetic modifiers from a meta‐mapping study of spike–wave discharge in mice; Genes, Brain and Behavior; (2024).

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    • Mechanisms for Cognitive Impairment in Epilepsy: Moving Beyond Seizures; Frontiers in Neurology; (2022).

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    • Differential regulation of gene expression pathways with dexamethasone and ACTH after early life seizures; bioRxiv; (2022).

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    • Fine Spike Timing in Hippocampal-Prefrontal Ensembles Predicts Poor Encoding and Underlies Behavioral Performance in Healthy and Malformed Brains; Cerebral Cortex; (2021).

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    • Distributed dynamic coding for spatial working memory in hippocampal-prefrontal networks; bioRxiv; (2019).

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    • Environmental enrichment normalizes hippocampal timing coding in a malformed hippocampus; PLoS ONE; (2018).

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    • Environmental Enrichment Normalizes Hippocampal Timing Coding in a Malformed Hippocampus; bioRxiv; (2017).

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    • Methodological standards and functional correlates of depth in vivo electrophysiological recordings in control rodents. A TASK1-WG3 report of the AES/ILAE Translational Task Force of the ILAE; Epilepsia; (2017).

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    • ACTH prevents deficits in fear extinction associated with early life seizures; Frontiers in Neurology; (2016).

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    • Antiepileptic drug treatment strategies in neonatal epilepsy; Progress in Brain Research; (2016).

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    • Short-range temporal interactions in sleep; Hippocampal spike avalanches support a large milieu of sequential activity including replay; PLoS ONE; (2016).

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    • Stimulation of glutamate receptors in the ventral tegmental area is necessary for serotonin-2 receptor-induced increases in mesocortical dopamine release; Neuroscience; (2015).

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    • Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide; Neurobiology of Disease; (2015).

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    • Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH; PLoS ONE; (2014).

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    • Focal epileptiform activity in the prefrontal cortex is associated with long-term attention and sociability deficits; Neurobiology of Disease; (2014).

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    • Altered short-term plasticity in the prefrontal cortex after early life seizures; Neurobiology of Disease; (2013).

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    • Thrombin facilitates seizures through activation of persistent sodium current; Annals of Neurology; (2012).

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    • Early-life seizures produce lasting alterations in the structure and function of the prefrontal cortex; Epilepsy and Behavior; (2011).

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