The Behavioral Tale of Two Manipulations: Surgical and Genetic

ISBN-10
1369234082
ISBN-13
9781369234084
Category
Convulsions
Pages
42
Language
English
Published
2016
Author
Daniel P. Petrus

Description

CHAPTER 1 Objective. The objective of this mouse behavior study was to examine if mice with a single neocortical freeze lesion insult developed chronic spontaneous epileptic seizures and, if so, what were the impacts of those seizures on behavior, if any? Methods. A unilateral, Single Freeze Lesion was made on postnatal day 0 – 1 pups to induce single neocortical microgyria in the Right S1 area (SFLS1R). Screw-free intracranial EEG electrode implantation was then performed and continuous 24 hour EEG recordings were made. Mice with (w/) and without (w/o) seizures were blindly tested in an automated behavioral apparatus in a novel open field (OF), light-dark box (L/D), social interaction (SI), and novel object recognition (NOR) tests. Results. The results of the EEG analysis showed that 50% (17/34) of age-matched SFLS1R mice developed chronic spontaneous ictal–discharges, which predominantly occurred during the NREM sleep stage. This behavioral assay revealed statistically significant altered behavior between mice w/ seizures compared to mice w/o seizures. In the OF test mice w/ seizures exhibited a significant reduction in exploratory locomotion. However, in the L/D and SI tests, mice w/ seizures exhibited a significant increase in exploratory activity. Finally, during the NOR test mice w/ seizures spent significantly more time with the familiar object as well as with the novel object. Interpretation. The results of this study show the first report of spontaneous chronic seizures, in vivo, in a rodent freeze lesion model of FCD. Using this model, the cause and effect of the seizures can be studied directly without confounding variables found in human patient populations. This study suggests that abnormal electrical activities occurring during sleep alone may cause major changes in an animal’s cognitive abilities and affective states. To our knowledge, this is the first report of seizure induced behavior changes in the FCD mouse model. CHAPTER 2 Objective. Genome wide association studies (GWAS) strongly implicate Ankyrin - G (ANK3) as a possible risk gene in mental disorders. This study took advantage of a previously developed transgenic mouse line with a targeted genetic disruption of the brain specific ANK3 exon – 1b isoform. The objective of this research was to study the behavior of ANK3 transgenic mice to look for insight into the neural mechanisms underlying ANK3 functions and its possible role in the pathophysiology of mental illness. Methods. This study used 50 day old male mice with three different genotypes: ANK3 wild – type+/+ (WT), heterozygous+/- (HT), and homozygous -/- (HM) mice. The test subjects were blindly tested in an automated behavioral apparatus in a novel open field (OF), light-dark box (L/D), social interaction (SI), and novel object recognition (NOR) tests. Results. The results of the behavioral tests showed that HM and HT mice displayed statistically significant difference in behavior compared to WT mice. HM mice had severe, observable ataxia and significantly less locomotion during the tests compared to WT or HT mice. Also, HT mice had significantly more locomotion during the tests compared to WT or HM mice. The NOR could not be completed due to HM mice complete lack of exploration of the objects. Interpretation. The results of the study show that ANK3 expression in the brain is required for normal locomotion. The presence of only one functional copy of the ANK3 gene showed to be enough to “rescue” normal locomotion, as in the case of the HT mice. Additionally, ANK3 HM mice have a varying degree of ataxia and some suffer from convulsive seizures that sometimes result in death.

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