| Autor: |
Hernan AE; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont, United States of America., Mahoney JM; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont, United States of America., Curry W; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont, United States of America., Richard G; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont, United States of America., Lucas MM; Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America., Massey A; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont, United States of America., Holmes GL; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont, United States of America., Scott RC; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, Vermont, United States of America.; University College London, Institute of Child Health, London, United Kingdom. |
| Abstrakt: |
Neurodevelopmental insults leading to malformations of cortical development (MCD) are a common cause of psychiatric disorders, learning impairments and epilepsy. In the methylazoxymethanol (MAM) model of MCDs, animals have impairments in spatial cognition that, remarkably, are improved by post-weaning environmental enrichment (EE). To establish how EE impacts network-level mechanisms of spatial cognition, hippocampal in vivo single unit recordings were performed in freely moving animals in an open arena. We took a generalized linear modeling approach to extract fine spike timing (FST) characteristics and related these to place cell fidelity used as a surrogate of spatial cognition. We find that MAM disrupts FST and place-modulated rate coding in hippocampal CA1 and that EE improves many FST parameters towards normal. Moreover, FST parameters predict spatial coherence of neurons, suggesting that mechanisms determining altered FST are responsible for impaired cognition in MCDs. This suggests that FST parameters could represent a therapeutic target to improve cognition even in the context of a brain that develops with a structural abnormality. |
