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Early Influences: Seizures during Infancy Influence Behavior in Young Adult Mice

Commentary There have been a number of large-scale epidemiologic studies that have associated childhood epilepsy with a variety of neurobehavioral comorbidities including cognitive delay, depression, anxiety, attention-deficit/hyperactivity disorder as well as autism spectrum disorder (e.g., [1, 2]). While some headway has been made into the neurobiological substrates that may contribute to seizure-related cognitive impairments, there have been relatively few studies that have attempted to address additional comorbidities. In addition, little is known to what extent seizure events that occur very early in life might impact cognition later in life. A recent study by Lugo et al. suggests that early-life seizures can produce fairly specific deficits in spatial learning, and alterations in the way that adult mice interact socially. In this study, seizures were induced repeatedly in young mice over the course of 5 days using the volatile convulsant flurothyl. Seizures were induced beginning at 7 days of age to emulate seizure activity in children less than 1 year old. Mice were subsequently tested as young adults (60 days old) in a variety of behavioral tasks designed to assess cognitive capacity and autistic-like behaviors. Consistent with previous work (3), Lugo et al. found that early-life seizures impair performance in the Morris water maze in which mice are trained to find an escape platform that is submerged just below the surface of the pool. Mice that had experienced early-life seizures took significantly longer to find the hidden platform during training and exhibited a less-selective search strategy 30 minutes following training during a probe trail in which the platform was removed. Of importance, mice in the early-life seizure group were able to learn the location of the platform when it was clearly marked, demonstrating that the deficits in the hidden platform version were not due to alterations in motor performance or visual acuity required to perform the task. In contrast, early-life seizures did not produce deficits in associative learning as assessed by Pavlovian fear conditioning. Mice in the early-life seizure group were able to learn that an auditory conditioned stimulus (CS) was predictive of a foot-shock. Unlike the Morris water maze, this form of learning, commonly referred to as cued conditioning, can be accomplished even when the functional integrity of the hippocampus has been compromised. Although the authors did not assess the impact of early-life seizures on the hippocampal-dependent form of fear conditioning, where context is used as the CS, the water maze data and cued conditioning data taken collectively suggest that the early-life seizures selectively impact hippocampal-dependent memory formation. In addition to selective deficits in spatial memory, mice in the early-life seizure group also exhibited deficits in social Early-Life Seizures Result in Deficits in Social Behavior and Learning.