RT Journal Article
SR Electronic
T1 Environmental Enrichment Normalizes Hippocampal Timing Coding in a Malformed Hippocampus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 130450
DO 10.1101/130450
A1 Amanda E. Hernan
A1 J. Matthew Mahoney
A1 Willie Curry
A1 Greg Richard
A1 Marcella M. Lucas
A1 Andrew Massey
A1 Gregory L. Holmes
A1 Rod C. Scott
YR 2017
UL http://biorxiv.org/content/early/2017/04/25/130450.abstract
AB Neurodevelopmental insults such as malformations of cortical development (MCD) are a common cause of psychiatric disorders, learning impairments and epilepsy. Animals with MCDs have impairments in spatial cognition that, remarkably, are improved by post-weaning environmental enrichment (EE). To establish the network-level mechanisms responsible for these impacts, 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 MCDs disrupt FST and place-modulated rate coding in hippocampal CA1 and that EE restores both to normal. Moreover, FST parameters predict spatial coherence of neurons, suggesting that mechanisms determining FST are critical for cognition. This suggests that FST parameters could represent a therapeutic target to improve cognition even in the context of a structurally abnormal brain.HIGHLIGHTSEnvironmental enrichment (EE) in rats with cortical malformations improves cognition.EE resolves impaired rate and timing coding of hippocampal pyramidal neurons.Taken together, circuit-level dynamics directly affect quality of the cognitive map.RESEARCH IN CONTEXT Insults during neurodevelopment, particularly those that result in physical malformations in the brain, lead to cognitive impairment, psychiatric disorders and epilepsy. Environmental enrichment (EE) improves cognitive outcome in patients and animal models with brain malformations. Understanding how EE can improve cognition at the level of neural networks can lead to new treatment targets. Remarkably, using an approach that mathematically models neuron firing we show that firing is mistimed in animals with malformations and that EE improves this abnormality. Importantly, timing abnormalities predict abnormalities in cognition at the single neuron level, suggesting that restoring timing could improve learning and memory deficits.