Home-cage monitoring ascertains signatures of ictal and interictal behavior in mouse models of generalized seizures

Epilepsy is a significant contributor to worldwide disability. In epilepsy, disability can be broadly divided into two components: ictal (pertaining to the burden of unpredictable seizures and associated medical complications including death) and interictal (pertaining to more pervasive debilitating...

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Bibliographic Details
Published in:	PloS one Vol. 14; no. 11; p. e0224856
Main Authors:	Jankovic, Miranda J, Kapadia, Paarth P, Krishnan, Vaishnav
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 07-11-2019 Public Library of Science (PLoS)
Subjects:	Analysis Animal models Animals Anticonvulsants - therapeutic use Anxiety Autism Behavior Behavior, Animal Biology and Life Sciences Cages Cognitive ability Comorbidity Complications Convulsions & seizures Death Disabilities Disease Models, Animal Drinking water Electroencephalography Emotional behavior Epilepsies, Myoclonic - pathology Epilepsy House mouse Humidity Latency Medical schools Medicine Medicine and Health Sciences Mice Monitoring, Physiologic Mortality Mutation NAV1.1 Voltage-Gated Sodium Channel - metabolism Neurology Nocturnal Pentylenetetrazole Pentylenetetrazole - administration & dosage Research and Analysis Methods Seizures Seizures (Medicine) Seizures - pathology Sheltering behavior Sleep Social Sciences Sodium channels (voltage-gated) United States > US
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Summary:	Epilepsy is a significant contributor to worldwide disability. In epilepsy, disability can be broadly divided into two components: ictal (pertaining to the burden of unpredictable seizures and associated medical complications including death) and interictal (pertaining to more pervasive debilitating changes in cognitive and emotional behavior). In this study, we objectively and noninvasively appraise aspects of ictal and interictal behavior in mice using instrumented home-cage chambers designed to assay kinematic and appetitive behavioral measures. Through daily intraperitoneal injections of the chemoconvulsant pentylenetetrazole (PTZ) applied to C57BL/6J mice, we coordinately measure how "behavioral severity" (complex dynamic changes in movement and sheltering behavior) and convulsive severity (latency and occurrence of convulsive seizures) evolve or kindle with repeated injections. By closely studying long epochs between PTZ injections, we identify an interictal syndrome of nocturnal hypoactivity and increased sheltering behavior which remits with the cessation of seizure induction. We observe elements of this interictal behavioral syndrome in seizure-prone DBA/2J mice and in mice with a pathogenic Scn1a mutation (modeling Dravet syndrome). Through analyzing their responses to PTZ, we illustrate how convulsive severity and "behavioral" severity are distinct and independent aspects of the overall severity of a PTZ-induced seizure. Our results illustrate the utility of an ethologically centered automated approach to quantitatively appraise murine expressions of disability in mouse models of seizures and epilepsy. In doing so, this study highlights the very unique psychopharmacological profile of PTZ.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0224856