The Effects of In Vitro Seizure-Like Activity on Actin Capping in Dendritic Spines
Date of Award
Master of Science in Biomedical Sciences
Jocelyn Lippman-Bell, PhD
Heather Montie, PhD
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 the dendritic spine actin cytoskeleton, which is coordinated by actin binding proteins (ABPs). ABPs regulate the density, morphology, and dynamic nature of dendritic spines through actin capping, branching, and turnover of the filamentous actin composing the spinal cytoskeleton.
Seizure activity in early life can cause permanent deficits to the CNS from secondary brain injuries. Early-life seizure (ELS) models demonstrate altered spine morphology as a potential secondary brain injury. ELS can also affect the functionality of ABPs, and a general 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 have depleted Eps8 protein in neurons and exhibit dendritic spine dysgenesis. In general, a loss in function of epidermal growth factor receptor kinase substrate 8 (Eps8) causes dysregulation of dendritic spine morphology and function. In the current study, we investigated the effects of seizure-like activity on Eps8 using an in vitro “seizure model” in rat primary hippocampal neurons.
After exposing neurons to in-vitro seizure-like conditions, we assessed Eps8 localization in apical dendrites, actin monomer mobility, and dendritic spine motility using immunocytochemistry, fluorescent recovery after photo bleaching (FRAP), and live-cell imaging. Our results indicate that seizure-like activity may alter Eps8 localization in apical dendrites of primary hippocampal neurons and deplete the structural plasticity of dendritic spines of the apical dendrites in a developmentally dependent manner. Ongoing work will examine this link further to determine whether Eps8 could be a possible therapeutic target to decrease cognitive deficits that can result from early-life seizures and lead to comorbid disabilities.
Nieder, Cassidy, "The Effects of In Vitro Seizure-Like Activity on Actin Capping in Dendritic Spines" (2020). PCOM Biomedical Studies Student Scholarship. 203.