Abstracts

Rationale: Individuals who have experienced epilepsy in early life have significantly greater rates of learning disabilities and intellectual deficiency than those who have not experienced seizures. Specifically, early life seizures (ELS) have been linked to robust deviations of spatial and temporal coding in both the medial prefrontal cortex (mPFC) and the hippocampus (HPC). However, the method by which ELS leads to the development of cognitive defects is not well characterized. Changes in circuit morphology as a result of ELS also have not been assessed with respect to differences in sex. In addition to concurrent experiments pertaining to electrophysiological alterations in neuronal activity during an active avoidance task as a result of ELS, we hypothesized that those electrophysiological and behavioral differences found in ELS groups would manifest in differential circuit morphology.

Methods: Sprague Dawley rats were split into an ELS group, which were put through a seizure inducing protocol where they were given 50 flurothyl induced seizures from P15 to P25, and a control group which were given no seizures. The animals were then trained on a spatially based active avoidance task, two consecutive training days of 8 ten-minute avoidance sessions. Ability to learn the task and strategies of active avoidance for each rat was evaluated. Electrophysiological recordings of both the mPFC and hippocampus were performed as described in Niedecker et al. 2021. After data was collected, the rats were perfused and their brain tissue was fixed and stained using a Golgi fixative kit to allow for the visualization of dendritic projections. Area CA1 was then imaged in Golgi stained sections. Using the ImageJ/Fiji plugin Simple Neurite Tracer, neurons with a pyramidal cell phenotype were traced throughout their apical and basal dendrites. Sholl analyses were performed on only the apical dendrites and the whole cell, including the basal dendrites, in order to quantify dendritic arborization of CA1 pyramidal neurons.

Results: ELS males exhibited avoidance impairments, whereas female rats were unaffected in comparison to non-ELS controls. ELS males also exhibited a reduced dendritic arborization throughout the extent of the apical dendrites of CA1 pyramical neurons, whereas ELS females showed little difference to male and female controls.

Conclusions: Early life seizures reduce an animal’s capacity for learning a spatially based task when compared to individuals who have not had seizures. Behavioral deficits in male rats as a result of ELS are also correlated with a reduction in the arborization of the apical dendrites of CA1 pyramidal neurons. The future aims of this project are to investigate the seemingly protective effect of the female sex on ELS deficits. Furthermore, we will determine whether the differentiated physiology between male and female ELS groups will affect the efficacy of optogentic restoration of circuit function in ELS males.

Funding: Please list any funding that was received in support of this abstract.: National Institute of Health. Grant Numbers: NS108296, NS108765; National Institute of General Medical Sciences. Grant Number: 8 P30 GM103498; National Center for Research Resources. Grant Number: 5 P30 RR032135.