Abstract
Patients with neuropsychiatric and neurological disorders often express limbic circuit abnormalities and deficits in information processing. While these disorders appear to have diverse etiologies, their common features suggest neurodevelopmental origins. Neurodevelopment is a prolonged process of diverse events including neurogenesis/apoptosis, axon pathfinding, synaptogenesis, and pruning, to name a few. The precise timing of the neurodevelopmental insult to these processes likely determines the resulting functional outcome. We used the epilepsy and schizophrenia-related gestational day 17 methylazoxymethanol acetate model to examine the impact of this timed neurodevelopmental insult on principal cell morphology and synaptic network function of the dorsal hippocampus (dHPC) circuit. Our observed structural and functional alterations in dHPC are compartment specific, indicating that adverse global exposure during gestation can produce specific alterations and distort information processing in neural circuits that underlie cognitive abilities.
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Acknowledgements
This work was supported by NIH-R01MH084038 and NIH-R25NS080686-06. The authors would like to thank Drs. Hsin-Yi Kao and Edith Lesburgueres for help generating control and GD17-MAM rats. We would also like to thank Yi-Wen Chen and Dr. Chiye Aoki for assistance with the Golgi studies. Preliminary reports of these data have been present at the Annual meetings for Society for Neuroscience (2016) and the Canadian Association for Neuroscience (2016).
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KCO, AVP, and MIP collected data, KCO and ERJL performed analyses, and KCO and AAF designed research and wrote the manuscript.
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All methods complied with Public Health and Service Policy on Humane Care and Use of Laboratory Animals and were approved by the New York University Animal Welfare Committee.
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O’Reilly, K.C., Levy, E.R.J., Patino, A.V. et al. Sub-circuit alterations in dorsal hippocampus structure and function after global neurodevelopmental insult. Brain Struct Funct 223, 3543–3556 (2018). https://doi.org/10.1007/s00429-018-1704-3
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DOI: https://doi.org/10.1007/s00429-018-1704-3