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A method for detecting functional activity related expression in gross brain regions, specific brain nuclei and individual neuronal cell bodies and their projections
Biological Procedures Online volume 9, pages 1–8 (2007)
Abstract
We have developed a system to visualize functionally activated neurons and their projections in the brain. This system utilizes a transgenic mouse, fos-tau-lacZ (FTL), which expresses the marker gene, lacZ, in neurons and their processes after activation by many different stimuli. This system allows the imaging of activation from the level of the entire brain surface, through to individual neurons and their projections. The use of this system involves detection of neuronal activation by histochemical or immunohistochemical detection of β-galactosidase (βgal), the product of the lacZ gene. Furthermore, the underlying brain state of the FTL mice determines the basal levels of expression of βgal. Here we describe in detail our protocols for detection of FTL expression in these mice and discuss the main variables which need to be considered in the use of these mice for the detection and mapping of functionally activated neurons, circuits and regions in the brain.
References
Chaudhuri A. Neural activity mapping with inducible transcription factors. Neuroreport 1997; 8:iii-vii.
Herdegen T, Leah JD. Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Rev 1998; 28:370–490.
Morgan JI, Curran T. Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci 1991; 14:421–451.
Herrera DG, Robertson HA. Activation of c-fos in the brain. Prog Neurobiol 1996; 50:83–107.
Callahan CA, Thomas JB. Tau-beta-galactosidase, an axon-targeted fusion protein. Proc Natl Acad Sci USA 1994; 91:5972–5976.
Wilson Y, Nag N, Davern P, Oldfield BJ, McKinley MJ, Greferath U, Murphy M. Visualization of functionally activated circuitry in the brain. Proc Natl Acad Sci USA 2002; 99:3252–3257.
Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates, 2nd ed. (San Diego: Academic Press, 2001).
Smith PD, McLean KJ, Murphy MA, Wilson Y, Murphy M, Turnley AM, Cook MJ. A brightness-area-product-based protocol for the quantitative assessment of antigen abundance in fluorescent immunohistochemistry. Brain Res Brain Res Protoc 2005; 15:21–29.
Greferath U, Nag N, Zele AJ, Bui BV, Wilson Y, Vingrys AJ, Murphy M. Fos-tau-LacZ mice expose light-activated pathways in the visual system. Neuroimage 2004; 23:1027–1038.
Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 2006; 7:697–709.
Murphy M, Greferath U, Nag N, Nithianantharajah J, Wilson YM. Tracing functional circuits using c-fos regulated expression of marker genes targeted to neuronal projections. Front Biosci 2004; 9:40–47.
Cragg B. Preservation of extracellular space during fixation of the brain for electron microscopy. Tissue Cell 1980; 12:63–72.
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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Murphy, M., Greferath, U. & Wilson, Y.M. A method for detecting functional activity related expression in gross brain regions, specific brain nuclei and individual neuronal cell bodies and their projections. Biol. Proced. Online 9, 1–8 (2007). https://doi.org/10.1251/bpo128
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DOI: https://doi.org/10.1251/bpo128