Early life seizures project

Early-life status epilepticus produces a high-functioning autism-like phenotype: deficit in social interaction and vocalization, enhanced anxiety, no cognitive impairment and altered functional connectivity within the hippocampus (CA3-CA1) and between the hippocampus and prefrontal cortex. In this study, we used a social memory paradigm to evaluate social memory and social motivation, high demand cognitive tasks (Barnes and Octagonal mazes) to evaluate working memory, reference memory and cognitive flexibility followed by gene and protein expression of molecules related to social behavior, reward system and synapse function. At postnatal day 9, male Wistar rats were subjected to pilocarpine-induced early-life status epilepticus (380mg/kg, i.p.) and the control group received 0.9% saline (0.1 ml/10 g). In adulthood, animals were probed to social recognition memory and cognitive function followed by gene and protein expressions in hypothalamus, hippocampus, amygdala and striatum. In social recognition paradigm, experimental animals spent lower time interacting with the same conspecific, with no enhancement as the familiar animal was replaced by a novel one. In training phase of Barnes maze, the latency to get into the escape cage did not differ between groups. In test phase, as the escape cage has been removed, the time to reach the escape hole did not differ between groups, but the experimental group distributed more evenly the time exploring the peripheral zones the maze, rather than the control group that stayed next to the target hole. In training (TRP) and test phases (TP) of the octagonal maze task, both groups spent similar time to complete the task, but the experimental group exhibited fewer working memory errors during TP with no difference in reference memory errors. The gene expression for oxytocin, oxytocin receptors, dopamine receptors (DR1 and DR2), synapsin and NT3 did not change in experimental group that exhibited higher level of oxytocin in hypothalamus and lower expression of its receptor in hippocampus.