Introduction: Neonatal seizures can cause dysregulation of excitatory synaptic activity that may contribute to the development of cognitive deficits later in life. While the mechanisms underlying this association are not known, one possibility is the regulation of dendritic spines, the postsynaptic structures of most of the excitatory synapses in the mammalian brain. These membranous protrusions function as chemical and electrical micro-compartments, transducing individual signals of excitatory neurotransmitters. Structural plasticity, the ability of spines to change their shape and thus their function in response to synaptic activity, underlies learning and memory, and many neurological diseases defined by altered cognitive abilities display dendritic spine dysgenesis. This shape change requires regulation of actin mesh-

works by actin binding proteins (ABPs) within dendritic spines. Decreased concentrations of functional ABPs induce abnormalities in the density, morphology, and dynamic nature of dendritic spines, resulting in changes in synaptic function such as hindered synaptic signal amplitude. Based upon these studies, we hypothesized that seizure activity causes deficits in the structural plasticity of dendritic spines via depletion of functional ABPs.

Methods: To investigate the molecular physiological consequences of uncontrolled, synaptic excitability on intracellular actin regulation, we used a zero magnesium model to induce in vitro seizure-like activity in rat hippocampal neurons. At multiple time points after zero Mg2+ exposure, we assessed localization of ABPs in dendritic spines using immunocytochemistry and

analyzed the motility of dendritic spines in response to excitatory stimulation using live-cell imaging of GFP-actin transfected neurons.

Results: Preliminary results show a neuronal age and time point dependent decrease in ABP localization and spine motility in dendritic spines after in vitro seizure-like activity.

Conclusions: Taken together, these data indicate that seizure-like activity can alter ABPs and baseline spine dynamics. Ongoing work will examine whether seizure-induced ABPs could affect structural plasticity of dendritic spines to determine the feasibility of ABPs as a therapeutic target to decrease cognitive deficits that can result from early-life seizures.