Abstract
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.
Highlights
Neurodevelopmental insults are common etiologies in many neurological diseases, including epilepsy, schizophrenia, cerebral palsy, and autism spectrum disorders
In order to understand the neural networks underpinning poor spatial cognition and improved cognition after environmental enrichment (EE) in MAM animals, we used in vivo electrophysiological tetrode recording of pyramidal cells in CA1 of the hippocampus (Fig 1)
To corroborate the above findings, and determine whether we identified a comprehensive set of timing parameters, we performed principal component analysis (PCA) on the set of bursty post-spike filters (PSFs)
Summary
Neurodevelopmental insults are common etiologies in many neurological diseases, including epilepsy, schizophrenia, cerebral palsy, and autism spectrum disorders. Malformations of cortical development (MCDs) are one result of an insult during neurodevelopment and are commonly identified in patients with significant cognitive impairments and seizures [1]. Cognitive impairments are a major driver of impaired quality of life and strategies that maximize cognition would be expected to have a major positive impact on outcomes. In the context of epilepsy, the main therapeutic strategies have targeted seizures in order to try to achieve cognitive improvements. This approach has had limited success, raising the issue of whether abnormal neural networks underlying cognitive impairments can be functionally.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
