期刊论文详细信息
Neural Development
Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures
Stephen J Eglen4  Seth GN Grant1  Andrew Morton2  Ellese Cotterill4  Paul Charlesworth3 
[1]Centre for Clinical Brain Sciences and Centre for Neuroregeneration, Chancellors Building, Edinburgh University, 49 Little France Crescent, Edinburgh, EH16 4SB, UK
[2]Current address: Centre for Integrative Physiology, University of Edinburgh School of Biomedical Sciences, Edinburgh, EH8 9XD, UK
[3]Current address: Department of Physiology, Development and Neuroscience, Physiological Laboratory, Downing Street, Cambridge, CB2 3EG, UK
[4]Cambridge Computational Biology Institute, University of Cambridge, Wilberforce Road, Cambridge, CB3 0WA, UK
关键词: Classification tree;    Support vector machine;    Principal component analysis;    Hippocampus;    Cortex;    Spontaneous activity;    Multielectrode array;   
Others  :  1146001
DOI  :  10.1186/s13064-014-0028-0
 received in 2014-10-01, accepted in 2014-12-11,  发布年份 2015
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【 摘 要 】

Background

Neural circuits can spontaneously generate complex spatiotemporal firing patterns during development. This spontaneous activity is thought to help guide development of the nervous system. In this study, we had two aims. First, to characterise the changes in spontaneous activity in cultures of developing networks of either hippocampal or cortical neurons dissociated from mouse. Second, to assess whether there are any functional differences in the patterns of activity in hippocampal and cortical networks.

Results

We used multielectrode arrays to record the development of spontaneous activity in cultured networks of either hippocampal or cortical neurons every 2 or 3 days for the first month after plating. Within a few days of culturing, networks exhibited spontaneous activity. This activity strengthened and then stabilised typically around 21 days in vitro. We quantified the activity patterns in hippocampal and cortical networks using 11 features. Three out of 11 features showed striking differences in activity between hippocampal and cortical networks: (1) interburst intervals are less variable in spike trains from hippocampal cultures; (2) hippocampal networks have higher correlations and (3) hippocampal networks generate more robust theta-bursting patterns. Machine-learning techniques confirmed that these differences in patterning are sufficient to classify recordings reliably at any given age as either hippocampal or cortical networks.

Conclusions

Although cultured networks of hippocampal and cortical networks both generate spontaneous activity that changes over time, at any given time we can reliably detect differences in the activity patterns. We anticipate that this quantitative framework could have applications in many areas, including neurotoxicity testing and for characterising the phenotype of different mutant mice. All code and data relating to this report are freely available for others to use.

【 授权许可】

   
2015 Charlesworth et al.; licensee BioMed Central.

【 预 览 】
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【 参考文献 】
  • [1]Blankenship AG, Feller MB: Mechanisms underlying spontaneous patterned activity in developing neural circuits. Nat Rev Neurosci 2010, 11:18-29.
  • [2]Leinekugel X, Khazipov R, Cannon R, Hirase H, Ben-Ari Y, Buzsáki G: Correlated bursts of activity in the neonatal hippocampus in vivo. Science 2002, 296:2049-52.
  • [3]Khazipov R, Sirota A, Leinekugel X, Holmes GL, Ben-Ari Y, Buzsáki G: Early motor activity drives spindle bursts in the developing somatosensory cortex. Nature 2004, 432:758-61.
  • [4]Hanganu IL, Ben-Ari Y, Khazipov R: Retinal waves trigger spindle bursts in the neonatal rat visual cortex. J Neurosci 2006, 26:6728-36.
  • [5]Seelke AMH, Blumberg MS: Developmental appearance and disappearance of cortical events and oscillations in infant rats. Brain Res 2010, 1324:34-42.
  • [6]Colonnese MT, Khazipov R: Slow activity transients’ in infant rat visual cortex: a spreading synchronous oscillation patterned by retinal waves. J Neurosci 2010, 30:4325-37.
  • [7]Johnstone AFM, Gross GW, Weiss DG, Schroeder OHU, Gramowski A, Shafer TJ: Microelectrode arrays: a physiologically based neurotoxicity testing platform for the 21st century. Neurotoxicology 2010, 31:331-50.
  • [8]Wagenaar DA, Pine J, Potter SM: An extremely rich repertoire of bursting patterns during the development of cortical cultures. BMC Neurosci 2006, 7:11. BioMed Central Full Text
  • [9]Rolston JD, Wagenaar DA, Potter SM: Precisely timed spatiotemporal patterns of neural activity in dissociated cortical cultures. Neuroscience 2007, 148:294-303.
  • [10]Soriano J, Rodríguez Martínez M, Tlusty T, Moses E: Development of input connections in neural cultures. Proc Natl Acad Sci USA 2008, 105:13758-63.
  • [11]Gullo F, Manfredi I, Lecchi M, Casari G, Wanke E, Becchetti A: Multi-electrode array study of neuronal cultures expressing nicotinic β2-V287L subunits, linked to autosomal dominant nocturnal frontal lobe epilepsy. An in vitro model of spontaneous epilepsy. Front Neural Circuits 2014, 8:87.
  • [12]Lisman JE: Bursts as a unit of neural information: making unreliable synapses reliable. Trends Neurosci 1997, 20:38-43.
  • [13]Eytan D, Marom S: Dynamics and effective topology underlying synchronization in networks of cortical neurons. J Neurosci 2006, 26:8465-76.
  • [14]Cutts CS, Eglen SJ: Detecting pairwise correlations in spike trains: an objective comparison of methods and application to the study of retinal waves. J Neurosci 2014, 34:14288-303.
  • [15]Wong RO, Meister M, Shatz CJ: Transient period of correlated bursting activity during development of the mammalian retina. Neuron 1993, 11:923-38.
  • [16]Godfrey KB, Eglen SJ: Theoretical models of spontaneous activity generation and propagation in the developing retina. Mol Biosyst 2009, 5:1527-35.
  • [17]Buzsáki G: Theta oscillations in the hippocampus. Neuron 2002, 33:325-40.
  • [18]James G, Witten D, Hastie T, Tibshirani R: An Introduction to Statistical Learning: With Applications in R. Springer, New York; 2014.
  • [19]Ito S, Yeh FC, Hiolski E, Rydygier P, Gunning DE, Hottowy P, et al.: Large-scale, high-resolution multielectrode-array recording depicts functional network differences of cortical and hippocampal cultures. PLoS One 2014, 9:e105324.
  • [20]Okamoto K, Ishikawa T, Abe R, Ishikawa D, Kobayashi C, Mizunuma M, et al.: Ex vivo cultured neuronal networks emit in vivo-like spontaneous activity. J Physiol Sci 2014, 64:421-31.
  • [21]Maccione A, Hennig MH, Gandolfo M, Muthmann O, van Coppenhagen J, Eglen SJ, et al.: Following the ontogeny of retinal waves pan-retinal recordings of population dynamics in the neonatal mouse. J Physiol 2013, 592:1545-63.
  • [22]Gramowski A, Jügelt K, Weiss DG, Gross GW: Substance identification by quantitative characterization of oscillatory activity in murine spinal cord networks on microelectrode arrays. Eur J Neurosci 2004, 19:2815-25.
  • [23]Mack CM, Lin BJ, Turner JD, Johnstone AFM, Burgoon LD, Shafer TJ: Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes. Neurotoxicology 2014, 40:75-85.
  • [24]MacLaren EJ, Charlesworth P, Coba MP, Grant SGN: Knockdown of mental disorder susceptibility genes disrupts neuronal network physiology in vitro. Mol Cell Neurosci 2011, 47:93-9.
  • [25]Mann EO, Kohl MM, Paulsen O. Distinct roles of GABAA and GABAB receptors in balancing and terminating persistent cortical activity. J Neurosci. 2009; 29:7513–18.
  • [26]Mao BQ, Hamzei-Sichani F, Aronov D, Froemke RC, Yuste R: Dynamics of spontaneous activity in neocortical slices. Neuron 2001, 32:883-98.
  • [27]Potter SM, DeMarse TB: A new approach to neural cell culture for long-term studies. J Neurosci Methods 2001, 110:17-24.
  • [28]Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, Friman O, et al.: CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol 2006, 7:R100. BioMed Central Full Text
  • [29]Nex Technologies. NeuroExplorer Manual. 2012. [http://www.neuroexplorer.com/downloads/NeuroExplorerManual.pdf]
  • [30]Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 1995, 57:289-300.
  • [31]R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria; 2014. [http://www.r-project.org]
  • [32]Eglen SJ, Weeks M, Jessop M, Simonotto J, Jackson T, Sernagor E: A data repository and analysis framework for spontaneous neural activity recordings in developing retina. Gigascience 2014, 3:3. BioMed Central Full Text
  • [33]Genes to Cognition: Hippocampus vs Cortex project. [http://github.com/sje30/g2chvc]
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