Effects of beta-catenin on dendritic morphology and simulated firing patterns in cultured hippocampal neurons.
Beta-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 beta-catenin, and we simulate the electrophysiological consequences of these changes. Compared to control neurons, cells overexpressing beta-catenin have dendritic arbors with significantly greater surface area and more branches, as well as different topological characteristics. To investigate possible effects of beta-catenin expression on the electrophysiological properties of neurons, we converted confocal images of neurons expressing beta-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 beta-catenin-expressing neurons contributes to significantly smaller action potential amplitude and greater sensitivity than seen in control neurons. As a consequence, beta-catenin-expressing neurons tended to exhibit higher spike rates and needed less excitation to induce firing. These findings show that beta-catenin, by modifying dendritic arborization, could have profound influences on the electrophysiological behavior of neurons.
Krichmar
Jeffrey L
JL
The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, California 92121, USA. krichmar@nsi.edu
Velasquez
David
D
Ascoli
Giorgio A
GA
D003198:Computer Simulation; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology*; D008954:Models, Biological; D009415:Nerve Net / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D051176:beta Catenin