Abstract
In this study, the effect of protein Tuberous sclerosis 2 (TSC2) on the dendritic spine density and length was demonstrated by using TSC2-RNA inactivation. In addition, the role of rapamycin, an antagonist of the molecular target of rapamycin, in the morphological changes of spine caused by TSC2 silencing was investigated. The features were extracted from high-resolution three-dimensional image stacks collected by two-photon laser scanning microscopy of green fluorescing pyramidal cells expressing TSC2-RNA interference (RNAi), or TSC2-RNAi and rapamycin treatment in rat hippocampal slice cultures. We proposed to apply the lognormal distribution method for feature extraction. The extracted features of three cases under investigation, namely, (1) green-fluorescent protein GFP vs TSC2-RNAi, (2) GFP vs TSC2-RNAi and rapamycin, and (3) TSC2-RNAi vs TSC2-RNAi and rapamycin, were analyzed by mutual information-based feature selection and evaluated by three classifiers, K-nearest neighbor, Perceptron, and two-layer neural networks. The results showed that both the spine density and length have significant morphological changes after TSC2-RNAi treatment. However, rapamycin treatment could reverse the effect of TSC2-RNAi on spine length but not on spine density. These results are consistent with the results reported in the scientific literature. Finally, we explored the application of pattern recognition method in a small sample with richer feature properties, namely bootstrap mutual information estimation and a mutual information-based feature selection method.
Similar content being viewed by others
References
Battiti, R. (1994) Using mutual information for selecting features in supervised neural net learning. IEEE Trans. Neural Netw. 5, 537–550.
Cover, T. M. and Thomas J. A. (1991) Elements of Information Theory. Wiley, New York.
Daniel, W. W. (1999) Biostatistics: A Foundation For Analysis in the Health Sciences. Wiley, New York.
Denk, W. and Svoboda, K. (1997) Photon upmanship: why multiphoton imaging is more than a gimmick. Neuron 18, 351–357.
Dougherty, E. R. (2001) Small sample issues for microarray-based classification. Comp. Functional Genom. 2, 28–34.
Duda, R. O., Hart, P. E., and Stork, D. G. (2001) Pattern Classification (2nd ed). John Wiley and Sons, New York.
Garey, L. J., Ong, W. Y., Patel, T. S., et al. (1998) Reduced dendritic spinedensity on cerebral cortical pyramidal neurons in schizophrenia, J. Neurol. Neurosurg. Psychiatry 65, 446–453.
Inoki, K., Li, Y., Zhu, T., Wu, J., and Guan, K. L. (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signaling. Nat. Cell Biol. 4, 648–657.
Irwin, S. A., Patel, B., Idupulapati, M., Harris, J. B., and Crisostomo, R. A. (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am. J. Med. Genet. 98, 161–167.
Koh, I. Y., Lindquist, W. B., Zito, K., Nimchinsky, E. A., and Svoboda, K. (2002) An image analysis algorithm for dendritic spines. Neural Comput. 14, 1283–1310.
Lendvai, B., Stern, E. A., Chen, B., and Svoboda, K. (2000) Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404, 876–881.
Lo, D. C., McAllister, A. K., and Katz, L. C. (1994) Neuronal transfection in brain slices using particle-mediated gene transfer. Neuron 13, 1263–1268.
Machado-Salas, J. P. (1984) Abnormal dendritic patterns and aberrant spine development in Bourneville's disease—a Golgi survey. Clin. Neuropathol. 3, 52–58.
Marin-Padilla, M. (1976) Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome, A Golgi Study. J. Comp. Neurol. 167, 63–81.
McManus, E. J. and Alessi, D. R. (2002) TSC1-TSC2: a complex tale of PKB-mediated S6K regulation. Nat. Cell Biol. 4, E214-E216.
Moser, M. B., Trommald, M., and Anderson, P. (1994) An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc. Natl. Acad. Sci. USA 91, 12,673–12,675.
Nimchinsky, E. A., Sabatini, B. L., and Svoboda, K. (2002) Structure and function of dendritic spines. Ann. Rev. Physiol. 64, 313–353.
Potter, C. J., Pedraza, L. G., and Xu, T. (2002) Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4, 658–665.
Rudelli, R. D., Brown, W. T., Wisniewski, K., et al. (1985) Adult fragile X syndrome. Cliniconeuropathologic findings. Acta Neuropathol. 67, 289–295.
Stoppini, L., Buchs, P. A., and Muller, D. (1991) A simple method for organotypic cultures of nervous tissue. J. Neurosci. Methods 37, 173–182.
Tavazoie, S. F., Alvarez, V. A., Ridenour, D. A., Kwiatkowski, D. J., and Sabatini, B. L. (2005) Regulation of neuronal morphology and function by the tumor suppressors TSC1 and TSC2. Nat. Neurosci. 8(12), 1727–1734.
Troyanskaya, O., Cantor, M., Sherlock, G., et al. (2001) Missing value estimation methods for DNA microarrays. Bioinformatics 17, 520–525.
Yuste, R. and Denk, W. (1995) Dendritic spines as basic functional units of neuronal integration. Nature 375, 682–684.
Zhou, X., Wang, X., and Dougherty, E. R. (2003a) Binarization of microarray data based on a mixture model. Mol. Cancer Ther. 2, 679–684.
Zhou, X., Wang, X., and Dougherty, E. R. (2003b) Missing value estimation based on linear and nonlinear regression with Bayesian gene selection. Bioinformatics 19, 2302–2307.
Zhou, X., Wang, X., and Dougherty, E. R. (2004) Nonlinear-probit gene classification using mutual-information and wavelet based feature selection. J. Biol. Syst. 12, 371–386.
Zhou, X., Cao, X., Perlman, Z., and Wong, S. T. C. (2005a) A computerized cellular imaging system for high content analysis in Monastrol suppressor screens. J. Biomedical Informat., 38 (in Press).
Zhou, X., Liu, K. L., Bradley, P., Perrimon, N., and Wong, S. T. C. (2005b) Towards automated cellular image segmentation for RNAi genome-wide screening. Lecture Notes in Computer Science (MICCAI2005), 3749, 885–892.
Zoubir, A. M. and Boashash, B. (1998) The bootstrap and its application in signal processing. IEEE Signal Process. Magazine 15, 56–76.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhou, X., Zhu, J., Liu, KY. et al. Mutual information-based feature selection in studying perturbation of dendritic structure caused by TSC2 inactivation. Neuroinform 4, 81–94 (2006). https://doi.org/10.1385/NI:4:1:81
Issue Date:
DOI: https://doi.org/10.1385/NI:4:1:81