Elsevier

EBioMedicine

Volume 7, May 2016, Pages 175-190
EBioMedicine

Research Paper
Temporal Coordination of Hippocampal Neurons Reflects Cognitive Outcome Post-febrile Status Epilepticus☆,☆☆

https://doi.org/10.1016/j.ebiom.2016.03.039Get rights and content
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Highlights

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    We induced prolonged febrile seizures in an animal model of febrile status epilepticus (FSE).

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    FSE animals were sorted by those that could learn an active avoidance spatial task and those that could not.

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    Cognitive outcome depended on network ability to temporally organize hippocampal place cells with theta oscillations.

Rats that experienced febrile status epilepticus (FSE) were trained on an active avoidance spatial task and sorted by those that were able to reach task criterion (FSE-L) and those that could not (FSE-NL). We found that the temporal organization of place cells within and between hippocampal subnetworks by local theta oscillations may be a primary determinant of spatial cognition. Differences in levels of temporal organization were evident in both FSE-L and FSE-NL and therefore point to physiological mechanisms that underpin the variability in cognitive outcomes that follow neurological insults experienced in early development and how negative outcomes may be prevented.

Abstract

The coordination of dynamic neural activity within and between neural networks is believed to underlie normal cognitive processes. Conversely, cognitive deficits that occur following neurological insults may result from network discoordination. We hypothesized that cognitive outcome following febrile status epilepticus (FSE) depends on network efficacy within and between fields CA1 and CA3 to dynamically organize cell activity by theta phase. Control and FSE rats were trained to forage or perform an active avoidance spatial task. FSE rats were sorted by those that were able to reach task criterion (FSE-L) and those that could not (FSE-NL). FSE-NL CA1 place cells did not exhibit phase preference in either context and exhibited poor cross-theta interaction between CA1 and CA3. FSE-L and control CA1 place cells exhibited phase preference at peak theta that shifted during active avoidance to the same static phase preference observed in CA3. Temporal coordination of neuronal activity by theta phase may therefore explain variability in cognitive outcome following neurological insults in early development.

Keywords

Cognition
Febrile status epilepticus
Hippocampal network
Temporal coordination

Cited by (0)

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Author Contributions: JB carried out the experiments, JB, GH and TZB designed experiments, KP induced febrile status epilepticus, JB, SS and RS carried out statistical analyses, JB, SB and PLS contributed custom software for data processing. All authors contributed to the writing of the manuscript.

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Acknowledgments: We are very appreciative to Dr. Colin Lever, Dr. John Huxter, Dr. Andre Fenton and Willie Curry for comments on early versions of the manuscript. We thank Dr. John Kleen for coding advice and Jonathan Blumberg for assistance with histology. Funded by National Institutes of Health grant NS073083 and the Michael J. Pietroniro Research Fund to GLH and National Institutes of Health grant NS078279 to GLH and TZB. We declare no conflicts of interest.

© 2016 The Authors. Published by Elsevier B.V.