A Standardized Protocol for Stereotaxic Intrahippocampal Administration of Kainic Acid Combined with Electroencephalographic Seizure Monitoring in Mice.

Pascal Bielefeld,Pascal Bielefeld,Mirjana Maletic-Savatic,Anne Anderson,Amanda Sierra,Amanda Sierra,Anne Anderson,Carlos P Fitzsimons,Amanda Sierra,Juan M Encinas,Carlos P Fitzsimons,Juan M Encinas,Anne Anderson,Juan M Encinas

doi:10.3389/fnins.2017.00160

Pascal Bielefeld, Pascal Bielefeld + Show 12 more

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https://doi.org/10.3389/fnins.2017.00160

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Lack of scientific reproducibility is a growing concern and weak experimental practices may contribute to irreproducibility. Here, we describe an optimized and versatile protocol for stereotaxic intrahippocampal administration of Kainic Acid (KA) in mice with a C57Bl6 background. In this protocol, KA administration is combined with in vivo recording of neuronal activity with wired and wireless setups. Following our protocol, KA administration results in a robust dose-dependent induction of low-level epileptiform activity or Status Epilepticus (SE) and induces previously characterized hallmarks of seizure-associated pathology. The procedure consists of three main steps: Craniotomy, stereotaxic administration of KA, and placement of recording electrodes in intrahippocampal, and subdural locations. This protocol offers extended possibilities compared to the systemic administration of KA, as it allows the researcher to accurately regulate the local dose of KA and resulting seizure activity, and permits the use and study of convulsive and non-convulsive KA doses, resulting in higher reproducibility and lower inter-individual variability and mortality rates. Caution should be taken when translating this procedure to different strains of mice as inter-strain sensitivity to KA has been described before. The procedure can be performed in ~1 h by a trained researcher, while intrahippocampal administration of KA without placing recording electrodes can be done in 25 min, and can be easily adapted to the titrated intrahippocampal administration of other drugs.

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Many available animal models of Mesial Temporal lobe epilepsy, and in particular systemic kainic acid (KA) administration, are induced by acute treatments that often are associated with high mortality and experimental variability rates (Hellier et al, 1998; McLin and Steward, 2006; Kienzler-Norwood et al, 2017)
Delivered KA may act on KA and AMPA receptors located both preand post-synaptically in pyramidal and granule cells, regulating neurotransmission (Vincent and Mulle, 2009), In contrast, systemic convulsants may act on the whole brain and target different circuits in brain regions enriched in KA receptors, including the cerebral cortex or the amygdala (Vincent and Mulle, 2009)
In our intrahippocampal administration model, we have observed largely the same effects independently of small differences in the coordinates used to inject KA into the dentate gyrus (DG), supporting the idea that a common circuit is activated

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Introduction

Many available animal models of Mesial Temporal lobe epilepsy (mTLE), and in particular systemic KA administration, are induced by acute treatments that often are associated with high mortality and experimental variability rates (Hellier et al, 1998; McLin and Steward, 2006; Kienzler-Norwood et al, 2017). It describes the local administration of KA into the mouse hippocampus using stereotaxic injection and simultaneous recording of EEG activity.

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