Impact Factor 3.267

The Frontiers in Neuroscience journal series is the 1st most cited in Neurosciences

This article is part of the Research Topic

Neuroanatomy and transgenic technologies

Editorial ARTICLE

Front. Neuroanat., 21 January 2015 | https://doi.org/10.3389/fnana.2014.00157

Neuroanatomy and transgenic technologies

  • 1Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, USA
  • 2Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
  • 3Baylor College of Medicine, Childrens Nutrition Research Ct, Houston, TX, USA
  • 4International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan

Gerald Edelman once wrote: “If someone held a gun to my head and threatened oblivion if I did not identify the single word most significant for understanding the brain, I would say ‘neuroanatomy.’ Indeed, perhaps the most important general observation that can be made about the brain is that its anatomy is the most important thing about it” (Edelman and Tononi, 2000).

Neuroscientists increasingly rely on techniques enabling them to manipulate genes in defined cell populations in the brain. In particular, engineered transgenes, which encode a variety of fluorescent reporter proteins, can be inserted into the genome or delivered into desired brain regions using viral vectors, thereby allowing the labeling of molecularly-defined populations of neurons or glial cells (Callaway, 2005). Transgenic technology can also be used to selectively delete genes in genetically-targeted cell populations (Nagy, 2000) or bi-directionally modulate electrical excitability using optogenetic or chemogenetic techniques (Aston-Jones and Deisseroth, 2013). One of the primary advantages of using transgenic reagents is to simplify the identification of targeted populations of neurons and their projections, which can be laborious using traditional techniques in neuroanatomy. In this research topic, we will be focusing on the application of transgenic technology to neuroanatomical questions and have collected up-to-date reviews and original articles that demonstrate the versatility and power of transgenic tools in advancing our knowledge of the nervous system. Kou et al. (2013) used a GAD67-GFP transgenic mouse to examine changes in components of GABAergic neurotransmission among neuronal populations in the dorsal cochlear nucleus, in a mouse model of noise-induced hearing loss. This was complemented by the article of Zhang et al. (2013), characterizing the efferent projections of adenosine A2A receptor-expressing neurons in the nucleus accumbens using a virally-mediated anterograde tracing method in adenosine A2A receptor-cre mice. In addition to its utility in tagging and tracing targeted neuronal populations, transgenic technology can be applied to the study of morphological and neurochemical changes occurring in the brains of animals lacking a specific gene. For instance, Xu et al. (2014) examined changes in CART expression in neurons of the Edinger–Westphal nucleus in leptin receptor deficient mice.

Needless to say, the study of the peripheral nervous system has also greatly benefited from the aforementioned transgenic tools (Braz et al., 2014). Several articles included in this research topic focused on the peripheral nervous system. We highly recommend the reading of the article by Le Pichon and Chesler (2014), as it is a comprehensive and thoughtful review entirely dedicated to mouse models useful for the manipulation and categorization of somatosensory neurons in the dorsal root ganglion. Many investigators and clinicians are also interested in identifying new ways of delivering transgenes, particularly ones with therapeutic value, to the brain by targeting neurons in the peripheral nervous system. In fact, it has been suggested that virally-mediated gene delivery to the human brain may have the potential to treat numerous neurological diseases (Janson et al., 2002). Three articles in this research topic highlighted the versatility of virally-mediated gene delivery to peripheral pathways. The original articles by Schuster et al. (2014a,b) and Salegio et al. (2014) described the central distribution of intrathecally-delivered adeno-associated viruses expressing reporter proteins. Finally, the article by Jara et al. (2014) focused on approaches for the retrograde labeling of spinal motor neurons using reporter proteins.

In spite of the growing number of sophisticated tools available to neuroscientists, currently available tools greatly limit our ability to collect high resolution images encompassing large areas of the mammalian nervous system (Lichtman and Denk, 2011). The opinion article by Pabba (2013) briefly discussed how the anatomical organization of the central nervous system, with a special emphasis on the amygdaloid complex, has increased in complexity during the course of evolution, while conserving a common basic plan, recognizable across animal species. Henceforth, studying the nervous system of lower organisms is immediately relevant to the understanding of the basic principles governing the anatomical organization of the mammalian nervous system (Amat et al., 2014). This research topic included two original articles focusing on the zebrafish nervous system. Using a zebrafish transgenic line expressing eGFP, Djenoune et al. (2014) described a poorly characterized group of specialized neurons that make contact with the cerebrospinal fluid. This was complemented by an article by Lopez-Schier et al. (Pinto-Teixeira et al., 2013) describing a novel method for the visualization of sensory hair-cell regeneration in the lateral line of transgenic zebrafish larvae using selective plane illumination microscopy (SPIM). The technique described in this latter article offers a unique model for the study of neuroplasticity in a living organism.

In summary, the anatomical complexity of the nervous system remains a subject of tremendous fascination among neuroscientists. Unraveling the myriad cells and circuits in the nervous system is as much a pressing question now as it was over 100 years ago in the time of Cajal and Golgi. In order to tackle this extraordinary complexity, powerful transgenic technologies are continually being developed, improved upon and used in the study of such diverse questions as cell lineage mapping, neural tract tracing, protein trafficking, neuronal excitability and morphological plasticity of dendritic spines and axonal arbors. In addition to giving neuroscientists an update on these rapidly evolving techniques used in neuroanatomy, we hope that the articles included in this research topic will spark new ideas among investigators interested in the “most important thing” about the brain—its anatomy.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

Amat, F., Lemon, W., Mossing, D. P., McDole, K., Wan, Y., Branson, K., et al. (2014). Fast, accurate reconstruction of cell lineages from large-scale fluorescence microscopy data. Nat. Methods 11, 951–958. doi: 10.1038/nmeth.3036

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Aston-Jones, G., and Deisseroth, K. (2013). Recent advances in optogenetics and pharmacogenetics. Brain Res. 1511, 1–5. doi: 10.1016/j.brainres.2013.01.026

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Braz, J., Solorzano, C., Wang, X., and Basbaum, A. I. (2014). Transmitting pain and itch messages: a contemporary view of the spinal cord circuits that generate gate control. Neuron 82, 522–536. doi: 10.1016/j.neuron.2014.01.018

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Callaway, E. M. (2005). Neural substrates within primary visual cortex for interactions between parallel visual pathways. Prog. Brain Res. 149, 59–64. doi: 10.1016/S0079-6123(05)49005-6

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Djenoune, L., Khabou, H., Joubert, F., Quan, F. B., Nunes Figueiredo, S., Bodineau, L., et al. (2014). Investigation of spinal cerebrospinal fluid-contacting neurons expressing PKD2L1: evidence for a conserved system from fish to primates. Front. Neuroanat. 8:26. doi: 10.3389/fnana.2014.00026

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Edelman, G., and Tononi, G. (2000). A Universe of Consciousness: How Matters Becomes Imagination. New York, NY: Basic Books.

Google Scholar

Janson, C., McPhee, S., Bilaniuk, L., Haselgrove, J., Testaiuti, M., Freese, A., et al. (2002). Clinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Hum. Gene Ther. 13, 1391–1412. doi: 10.1089/104303402760128612

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Jara, J. H., Genc, B., Klessner, J. L., and Ozdinler, P. H. (2014). Retrograde labeling, transduction, and genetic targeting allow cellular analysis of corticospinal motor neurons: implications in health and disease. Front. Neuroanat. 8:16. doi: 10.3389/fnana.2014.00016

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Kou, Z. Z., Qu, J., Zhang, D. L., Li, H., and Li, Y. Q. (2013). Noise-induced hearing loss is correlated with alterations in the expression of GABAB receptors and PKC gamma in the murine cochlear nucleus complex. Front. Neuroanat. 7:25. doi: 10.3389/fnana.2013.00025

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Le Pichon, C. E., and Chesler, A. T. (2014). The functional and anatomical dissection of somatosensory subpopulations using mouse genetics. Front. Neuroanat. 8:21. doi: 10.3389/fnana.2014.00021

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Lichtman, J. W., and Denk, W. (2011). The big and the small: challenges of imaging the brain's circuits. Science 334, 618–623. doi: 10.1126/science.1209168

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Nagy, A. (2000). Cre recombinase: the universal reagent for genome tailoring. Genesis 26, 99–109. doi: 10.1002/(SICI)1526-968X(200002)26:2<99::AID-GENE1>3.0.CO;2-B

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Pabba, M. (2013). Evolutionary development of the amygdaloid complex. Front. Neuroanat. 7:27. doi: 10.3389/fnana.2013.00027

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Pinto-Teixeira, F., Muzzopappa, M., Swoger, J., Mineo, A., Sharpe, J., and Lopez-Schier, H. (2013). Intravital imaging of hair-cell development and regeneration in the zebrafish. Front. Neuroanat. 7:33. doi: 10.3389/fnana.2013.00033

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Salegio, E. A., Streeter, H., Dube, N., Hadaczek, P., Samaranch, L., Kells, A. P., et al. (2014). Distribution of nanoparticles throughout the cerebral cortex of rodents and non-human primates: implications for gene and drug therapy. Front. Neuroanat. 8:9. doi: 10.3389/fnana.2014.00009

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Schuster, D. J., Belur, L. R., Riedl, M. S., Schnell, S. A., Podetz-Pedersen, K. M., Kitto, K. F., et al. (2014b). Supraspinal gene transfer by intrathecal adeno-associated virus serotype 5. Front. Neuroanat. 8:66. doi: 10.3389/fnana.2014.00066

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Schuster, D. J., Dykstra, J. A., Riedl, M. S., Kitto, K. F., Belur, L. R., McIvor, R. S., et al. (2014a). Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse. Front. Neuroanat. 8:42. doi: 10.3389/fnana.2014.00042

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Xu, L., Janssen, D., van der Knaap, N., Roubos, E. W., Leshan, R. L., Myers, M. G. Jr., et al. (2014). Integration of stress and leptin signaling by CART producing neurons in the rodent midbrain centrally projecting Edinger-Westphal nucleus. Front. Neuroanat. 8:8. doi: 10.3389/fnana.2014.00008

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Zhang, J. P., Xu, Q., Yuan, X. S., Cherasse, Y., Schiffmann, S. N., de Kerchove d'Exaerde, A., et al. (2013). Projections of nucleus accumbens adenosine A2A receptor neurons in the mouse brain and their implications in mediating sleep-wake regulation. Front. Neuroanat. 7:43. doi: 10.3389/fnana.2013.00043

Pubmed Abstract | Pubmed Full Text | CrossRef Full Text | Google Scholar

Keywords: mouse models, transgenic, tracing, morphology, neurochemistry

Citation: Jackson AC, Liu C, Fukuda M, Lazarus M and Gautron L (2015) Neuroanatomy and transgenic technologies. Front. Neuroanat. 8:157. doi: 10.3389/fnana.2014.00157

Received: 25 November 2014; Accepted: 02 December 2014;
Published online: 21 January 2015.

Edited and reviewed by: Javier DeFelipe, Cajal Institute, Spain

Copyright © 2015 Jackson, Liu, Fukuda, Lazarus and Gautron. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: laurent.gautron@utsouthwestern.edu