The Effects of In Vitro Seizure‐like Activity on Structural Plasticity of Dendritic Spines

Abstract

Most excitatory synapses in the mammalian brain connect to dendritic spines. These membranous protrusions function as chemical and electrical micro‐compartments, transducing individual signals of excitatory neurotransmitters from axonal boutons. Structural plasticity, the ability of spines to change their shape and thus their function in response to synaptic activity, underlies learning and memory. This shape change requires regulation of actin mesh‐works, which are regulated by actin binding proteins (ABPs) within spines. Decreased concentrations of functional ABPs induce abnormalities in the density, morphology, and dynamic nature of dendritic spines. Early‐life seizure models demonstrate altered spine morphology, and a decrease in ABPs hinders synaptic signal amplitudes. Further, neonatal seizures are linked to cognitive deficits later in life, including autistic‐like behaviors, and patients with autism spectrum disorder express depleted concentrations of endogenous ABPs and exhibit dendritic spine dysgenesis. Based upon these findings, we hypothesized that seizure‐like activity causes deficits in the structural plasticity of dendritic spines via depletion of functional ABPs. To investigate the physiological consequences of uncontrolled, synaptic excitability on intracellular actin regulation at the molecular level, we induced in vitro seizure‐like activity in primary, rat hippocampal neurons using a zero magnesium model. At multiple time points after this event, we assessed localization of ABPs using immunocytochemistry, actin turnover employing fluorescent recovery after photo bleaching, and spine and actin dynamics in response to stimulation utilizing live‐cell imaging in GFP‐actin transfected neurons. Preliminary results show a decrease in localization of ABPs to dendritic spines and an increase in spine motility after in vitro seizure‐like activity in cultured hippocampal neurons. Taken together, these data indicate that seizures may alter ABPs in a model that also shows changes in spine dynamics and structural plasticity. Ongoing work will examine this link further to determine if ABPs could be a possible therapeutic target to decrease cognitive deficits that can result from early‐life seizures and lead to intellectual disabilities.Support or Funding InformationCCDA: Center for Chronic Disorders of Aging