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MRI-guided stereotaxic brain surgery in the infant and adult common marmoset

Abstract

In the past decade, the New World common marmoset (Callithrix jacchus) has taken a seminal position in neurobiological research, fueled in part by its smooth cortical sheet, which allows cortical areas to be easily accessed by current technologies on the dorsal surface of the brain. In this protocol, we describe a method for the precision placement of agents (e.g., tracers or neurotoxins) into small brain regions of the infant and adult marmoset, using an MRI-guided approach. This strategy uses a protocol for prolonged anesthesia without the need for intubation that we have recently developed, alongside appropriate analgesia and monitoring. The protocol can be readily adapted to be used together with advanced research techniques, such as two-photon microscopy and optical imaging. Including a 5-d postoperative care plan, this protocol takes 7 d to complete. The protocol requires a team of personnel experienced in marmoset care and handling, and small-animal neurosurgery; an assistant for monitoring the animal and assisting with anesthesia; and an MRI technician.

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Figure 1: Cranial fiducial marker.
Figure 2: Infant gaseous anesthesia induction box.
Figure 3: Custom-built MRI-compatible stereotaxic frame, injection and MRI equipment and facemask for marmoset neurosurgery.
Figure 4: Method of calculation of stereotaxic coordinates from T2 MRI images for intracerebral injection.
Figure 5: Examples of MRI images and photomicrographs of an infant and adult marmosets demonstrating accuracy of MRI-guided stereotaxic injection of various agent.

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References

  1. Missler, M. et al. Developmental biology of the common marmoset: proposal for a 'postnatal staging'. J. Med. Primatol. 21, 285–298 (1992).

    CAS  PubMed  Google Scholar 

  2. Schultz-Darken, N., Braun, K.M. & Emborg, M.E. Neurobehavioral development of common marmoset monkeys. Dev. Psychobiol. 58, 141–158 (2016).

    Article  Google Scholar 

  3. Sasaki, E. et al. Generation of transgenic non-human primates with germline transmission. Nature 459, 523–527 (2009).

    Article  CAS  Google Scholar 

  4. Sasaki, E. Prospects for genetically modified non-human primate models, including the common marmoset. Neurosci. Res. 93, 110–115 (2015).

    Article  CAS  Google Scholar 

  5. Rensing, S. & Oerke, A.-K. Husbandry and management of New World species: marmosets and tamarins. Lab. Primate 145–162 (2005).

  6. Flecknell, P.A. 7 - Anaesthesia of common laboratory species. In Laboratory Animal Anaesthesia 2nd edn. (ed. Flecknell, P.A.) 159–223 (Academic Press, 1996).

  7. Whelan, G., James, M.F., Samson, N.A. & Wood, N.I. Anaesthesia of the common marmoset (Callithrix jacchus) using continuous intravenous infusion of alphaxalone/alphadalone. Lab. Anim. 33, 24–29 (1999).

    Article  CAS  Google Scholar 

  8. Bakker, J. et al. Comparison of three different sedative-anaesthetic protocols (ketamine, ketamine-medetomidine and alphaxalone) in common marmosets (Callithrix jacchus). BMC Vet. Res. 9, 113 (2013).

    Article  Google Scholar 

  9. Warner, C.E. et al. Preservation of vision by the pulvinar following early-life primary visual cortex lesions. Curr. Biol. 25, 424–434 (2015).

    Article  CAS  Google Scholar 

  10. Warner, C.E., Kwan, W.C. & Bourne, J.A. The early maturation of visual cortical area MT is dependent on input from the retinorecipient medial portion of the inferior pulvinar. J. Neurosci. 32, 17073–17085 (2012).

    Article  CAS  Google Scholar 

  11. Teo, L. & Bourne, J.A. A reproducible and translatable model of focal ischemia in the visual cortex of infant and adult marmoset monkeys. Brain Pathol. 24, 459–474 (2014).

    Article  Google Scholar 

  12. Mitchell, J.F., Reynolds, J.H. & Miller, C.T. Active vision in marmosets: a model system for visual neuroscience. J. Neurosci. 34, 1183–1194 (2014).

    Article  CAS  Google Scholar 

  13. Mitchell, J.F. & Leopold, D.A. The marmoset monkey as a model for visual neuroscience. Neurosci. Res. 93, 20–46 (2015).

    Article  Google Scholar 

  14. Marmoset Genome, S. & Analysis, C. The common marmoset genome provides insight into primate biology and evolution. Nat. Genet. 46, 850–857 (2014).

    Article  Google Scholar 

  15. Paxinos, G., Watson, C., Petrides, M., Rosa, M.G. & Tokuno, H. The Marmoset Brain in Stereotaxic Coordinates 1st edn., 324 (Elsevier Academic Press, 2012).

  16. Stephan, H., Baron, G. & Schwerdtfeger, W.K. The Brain of the Common Marmoset (Callithrix jacchus) 1st edn. (Springer-Verlag, 1980).

  17. Palazzi, X. & Bordier, N. The Marmoset Brain in Stereotaxic Coordinates 1st edn., IV, 60, (Springer-Verlag, 2008).

  18. Tokuno, H., Tanaka, I., Umitsu, Y., Akazawa, T. & Nakamura, Y. Web-accessible digital brain atlas of the common marmoset (Callithrix jacchus). Neurosci. Res. 64, 128–131 (2009).

    Article  Google Scholar 

  19. Newman, J.D. et al. A combined histological and MRI brain atlas of the common marmoset monkey, Callithrix jacchus. Brain Res. Rev. 62, 1–18 (2009).

    Article  Google Scholar 

  20. Krauze, M.T. et al. Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents. J. Neurosurg. 103, 923–929 (2005).

    Article  Google Scholar 

  21. Gill, T. et al. In vitro and in vivo testing of a novel recessed-step catheter for reflux-free convection-enhanced drug delivery to the brain. J. Neurosci. Methods 219, 1–9 (2013).

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank W. Kwan and Q. Wu for their assistance with surgeries and imaging, respectively, and A. Gibbon and T. Tecirlioglu for their assistance with the postsurgical monitoring sheet. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. This work was supported by an NHMRC Project Grant (APP1042893) and by ARC SRI (Stem Cells Australia). J.A.B. is supported by an NHMRC Senior Research Fellowship (APP1077677).

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Authors

Contributions

I.-C.M. designed the MRI-guided protocol, performed the surgeries and wrote the manuscript; P.A.F. co-designed the anesthesia regimen and edited the manuscript; J.A.B. mentored the other authors, designed the protocol, obtained funding, performed the surgeries and wrote the manuscript.

Corresponding author

Correspondence to James A Bourne.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Supplementary Table 1 (PDF 144 kb)

Supplementary Data 1

Supplementary Data 1 - 3D facemask (ZIP 240 kb)

Supplementary Data 2

Supplementary Data 2 - 3D facemask (PDF 178 kb)

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Mundinano, IC., Flecknell, P. & Bourne, J. MRI-guided stereotaxic brain surgery in the infant and adult common marmoset. Nat Protoc 11, 1299–1308 (2016). https://doi.org/10.1038/nprot.2016.076

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