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Effects of ß-Catenin on Dendritic Morphology and Simulated Firing Patterns in Cultured Hippocampal Neurons

¹ The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, California 92121
² Department of Psychology, George Mason University, Fairfax, Virginia 22030
³ Krasnow Institute for Advanced Study, George Mason University, MS 2A1, Fairfax, Virginia 22030

^* To whom correspondence should be addressed. krichmar{at}nsi.edu

ß-catenin is an intracellular signaling molecule that has been shown to be important in activity-dependent dendritic morphogenesis. Here, we investigate the detailed morphological changes elicited in dendritic arbors of cultured hippocampal neurons by overexpression of ß-catenin, and we simulate the electrophysiological consequences of these changes. Compared to control neurons, cells overexpressing ß-catenin have dendritic arbors with significantly greater surface area and more branches, as well as different topological characteristics. To investigate possible effects of ß-catenin expression on the electrophysiological properties of neurons, we converted confocal images of neurons expressing ß-catenin into computational simulator formats using parameters that evenly distributed voltage-dependent channels across the cells’ membranes. In simulated current clamp experiments, somata were injected with a normalized current such that the observed electrophysiological differences in the neurons would be due only to morphological differences. We found that the morphology of ß-catenin-expressing neurons contributes to significantly smaller action potential amplitude and greater sensitivity than seen in control neurons. As a consequence, ß-catenin-expressing neurons tended to exhibit higher spike rates and needed less excitation to induce firing. These findings show that ß-catenin, by modifying dendritic arborization, could have profound influences on the electrophysiological behavior of neurons.