期刊论文详细信息
BMC Bioinformatics
Statistical analysis of dendritic spine distributions in rat hippocampal cultures
Aruna Jammalamadaka1  Sourav Banerjee2  Bangalore S Manjunath1  Kenneth S Kosik2 
[1] Department of Electrical and Computer Engineering, University of California Santa Barbara, Santa Barbara, CA, USA
[2] Department of Molecular and Cellular Neurobiology, University of California Santa Barbara, Santa Barbara, CA, USA
关键词: Neuronal growth;    Point processes;    Spatial statistics;    Morphological modeling;    Linear network K-function;    Rat hippocampal culture;    Dendritic spines;   
Others  :  1087748
DOI  :  10.1186/1471-2105-14-287
 received in 2013-02-07, accepted in 2013-09-16,  发布年份 2013
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【 摘 要 】

Background

Dendritic spines serve as key computational structures in brain plasticity. Much remains to be learned about their spatial and temporal distribution among neurons. Our aim in this study was to perform exploratory analyses based on the population distributions of dendritic spines with regard to their morphological characteristics and period of growth in dissociated hippocampal neurons. We fit a log-linear model to the contingency table of spine features such as spine type and distance from the soma to first determine which features were important in modeling the spines, as well as the relationships between such features. A multinomial logistic regression was then used to predict the spine types using the features suggested by the log-linear model, along with neighboring spine information. Finally, an important variant of Ripley’s K-function applicable to linear networks was used to study the spatial distribution of spines along dendrites.

Results

Our study indicated that in the culture system, (i) dendritic spine densities were "completely spatially random", (ii) spine type and distance from the soma were independent quantities, and most importantly, (iii) spines had a tendency to cluster with other spines of the same type.

Conclusions

Although these results may vary with other systems, our primary contribution is the set of statistical tools for morphological modeling of spines which can be used to assess neuronal cultures following gene manipulation such as RNAi, and to study induced pluripotent stem cells differentiated to neurons.

【 授权许可】

   
2013 Jammalamadaka et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Irwin S, Patel B, Idupulapati M, Harris J, Crisostomo R, Larsen B, Kooy F, Willems P, Cras P, Kozlowski P, et al.: Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: A quantitative examination. Am J Med Genet 2001, 98(2):161-167.
  • [2]Yuste R: Dendritic spines and distributed circuits. Neuron 2011, 71(5):772-781.
  • [3]Harnett M, Makara J, Spruston N, Kath W, Magee J: Synaptic amplification by dendritic spines enhances input cooperativity. Nature 2012, 491:599-602.
  • [4]Harris K, Kater S: Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci 1994, 17:341-371.
  • [5]Kaech S, Banker G: Culturing hippocampal neurons. Nature Protoc 2007, 1(5):2406-2415.
  • [6]Mukai J, Dhilla A, Drew L, Stark K, Cao L, MacDermott A, Karayiorgou M, Gogos J: Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat Neurosci 2008, 11(11):1302-1310.
  • [7]Cheetham C, Hammond M, McFarlane R, Finnerty G: Altered sensory experience induces targeted rewiring of local excitatory connections in mature neocortex. J Neurosci 2008, 28(37):9249-9260.
  • [8]Schratt G, Tuebing F, Nigh E, Kane C, Sabatini M, Kiebler M, Greenberg M: A brain-specific microRNA regulates dendritic spine development. Nature 2006, 439(7074):283-289.
  • [9]Mamaghani MJ, Andersson M, Krieger P: Spatial point pattern analysis of neurons using Ripley’s K-function in 3D. Front Neuroinformatics 2010, 4(0):1-10.
  • [10]Bell M, Grunwald G: Mixed models for the analysis of replicated spatial point patterns. Biostatistics 2004, 5(4):633-648.
  • [11]Millet L, Collens M, Perry G, Bashir R: Pattern analysis and spatial distribution of neurons in culture. Integr Biol 2011, 3(12):1167-1178.
  • [12]Harkness R, Isham V: A bivariate spatial point pattern of ants’ nests. Appl Stat 1983, 32(3):293-303.
  • [13]Mencuccini M, Martinez-Vilalta J, Piñol J, Loepfe L, Burnat M, Alvarez X, Camacho J, Gil D: A quantitative and statistically robust method for the determination of xylem conduit spatial distribution. Am J Bot 2010, 97(8):1247-1259.
  • [14]Yadav A, Gao Y, Rodriguez A, Dickstein D, Wearne S, Luebke J, Hof P, Weaver C: Morphologic evidence for spatially clustered spines in apical dendrites of monkey neocortical pyramidal cells. J Comp Neurol 2012, 520:2888-2902.
  • [15]Okabe A, Yamada I: The K-function method on a network and its computational implementation. Geogr Anal 2001, 33(3):271-290.
  • [16]Zhao C, Teng E, Summers R Jr, Ming G, Gage F: Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 2006, 26:3-11.
  • [17]Banker G, Goslin K: Culturing Nerve Cells. Cambridge, MA USA: MIT press; 1998.
  • [18]Baddeley A, Turner R: Spatstat: an R package for analyzing spatial point patterns. J Stat Softw 2005, 12(6):1-42. [ http://www.jstatsoft.org webcite, ISSN: 1548–7660]
  • [19]Meijering E, Jacob M, Sarria JCF, Steiner P, Hirling H, Unser M: Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images. Cytom Part A 2004, 58(2):167-176.
  • [20]Vallotton P, Lagerstrom R, Sun C, Buckley M, Wang D, Silva MD, Tan SS, Gunnersen J: Automated analysis of neurite branching in cultured cortical neurons using HCA-vision. Cytom Part A 2007, 71(10):889-895.
  • [21]Meijering E: Neuron tracing in perspective. Cytom Part A 2010, 77(7):693-704.
  • [22]Rodriguez A, Ehlenberger D, Dickstein D, Hof P, Wearne S: Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS ONE 2008, 3(4):e1997. doi:10.1371/journal.pone.0001997.
  • [23]Wearne S, Rodriguez A, Ehlenberger D, Rocher A, Hendersion S, Hof P: New Techniques for imaging, digitization and analysis of three-dimensional neural morphology on multiple scales. Neuroscience 2005, 136:661-680.
  • [24]Dumitriu D, Rodriguez A, Morrison J: High-throughput, detailed, cell-specific neuroanatomy of dendritic spines using microinjection and confocal microscopy. Nat Protoc 2011, 6(9):1391-1411.
  • [25]The DIADEM Scientific Challenge http://diademchallenge.org/ webcite. [Accessed: 30/09/2012].
  • [26]McCullagh P, Nelder J: Generalized Linear Models. London: Chapman & Hall/CRC; 1989.
  • [27]Chambers J, Hastie T, et al.: Statistical Models in S. London: Chapman & Hall; 1992.
  • [28]Hilbe J: Logistic Regression Models. London: CRC Press; 2009.
  • [29]Venables WN, Ripley BD: Modern Applied Statistics With S, fourth edition. New York: Springer; 2002. http://www.stats.ox.ac.uk/pub/MASS4 webcite. [ISBN 0-387-95457-0].
  • [30]Kass R, Raftery A: Bayes factors. J Am Stat Assoc 1995, 90(430):773-795.
  • [31]Ripley B: Spatial Statistics, Volume 24. New York, NY, USA: Wiley Online Library; 1981.
  • [32]Wilk M, Gnanadesikan R: Probability plotting methods for the analysis for the analysis of data. Biometrika 1968, 55:1-17.
  • [33]Govindarajan A, Israely I, Huang SY, Tonegawa S: The dendritic branch is the preferred integrative unit for protein synthesis-dependent LTP. Neuron 2011, 69:132-146.
  • [34]Harvey CD, Svoboda K: Locally dynamic synaptic learning rules in pyramidal neuron dendrites. Nature 2007, 450(7173):1195-1200.
  • [35]Ang Q, Baddeley A, Nair G: Geometrically corrected second order analysis of events on a linear network, with applications to ecology and criminology. Scand J Stat 2011, 39:591-617.
  • [36]Diggle PJ: Statistical Analysis of Spatial Point Patterns. New York: Oxford University Press Inc.; 2003.
  • [37]Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodological) 1995, 57(1):289-300.
  • [38]Storey J: A direct approach to false discovery rates. J R Stat Soc: Ser B (Statistical Methodology) 2002, 64(3):479-498.
  • [39]Dabney A, Storey JD, Warnes GR: qvalue: Q-value Estimation for False Discovery Rate Control. http://bioconductor.org/packages/2.12/bioc/html/qvalue.html webcite [R package version 1.28.0].
  • [40]Kvilekval K, Fedorov D, Obara B, Singh A, Manjunath B: Bisque: a platform for bioimage analysis and management. Bioinformatics 2010, 26(4):544-552. http://vision.ece.ucsb.edu/publications/kvilekval_Bioinformatics_2010.pdf webcite
  • [41]Ascoli G, Donohue D, Halavi M: NeuroMorpho. Org: a central resource for neuronal morphologies. J Neurosci 2007, 27(35):9247-9251.
  • [42]Sholl D: Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 1953, 87(Pt 4):387.
  • [43]Baddeley A, Turner R: Practical maximum pseudolikelihood for spatial point patterns. Aust N Z J Stat 2000, 42(3):283-322.
  • [44]Diggle P, Gates D, Stibbard A: A nonparametric estimator for pairwise-interaction point processes. Biometrika 1987, 74(4):763-770.
  • [45]Diggle P, Gratton R: Monte Carlo methods of inference for implicit statistical models. J R Stat Soc Ser B (Methodological) 1984, 46(2):193-227.
  • [46]Qiang L, Fujita R, Yamashita T, Angulo S, Rhinn H, Rhee D, Doege C, Chau L, Aubry L, Vanti W, et al.: Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 2011, 146(3):359-371.
  • [47]Brennand K, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, et al.: Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011, 473(7346):221-225.
  • [48]Egawa N, Kitaoka S, Tsukita K, Naitoh M, Takahashi K, Yamamoto T, Adachi F, Kondo T, Okita K, Asaka I, et al.: Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci Transl Med 2012, 4(145):145ra104-145ra104.
  • [49]Marchetto M, Gage F: Modeling brain disease in a dish: really? Cell Stem Cell 2012, 10(6):642-645.
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