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Head-mounted central venous access during optical recordings and manipulations of neural activity in mice

Nature Protocols volume 19, pages 960–983 (2024)Cite this article

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Abstract

Establishing reliable intravenous catheterization in mice with optical implants allows the combination of neural manipulations and recordings with rapid, time-locked delivery of pharmacological agents. Here we present a procedure for handmade jugular vein catheters designed for head-mounted intravenous access and provide surgical and postoperative guidance for improved survival and patency. A head-mounted vascular access point eliminates the need for a back-mounted button in animals already receiving neural implants, thereby reducing sites of implantation. This protocol, which is readily adoptable by experimenters with previous training and experience in mouse surgery, enables repeated fiber photometry recordings or optogenetic manipulation during drug delivery in adult mice that are awake and behaving, whether head fixed or freely moving. With practice, an experienced surgeon requires ~30 min to perform catheterization on each mouse. Altogether, these techniques facilitate the reliable and repeated delivery of pharmacological agents in mouse models while simultaneously recording at high temporal resolution and/or manipulating neural populations.

Key points

  • This protocol details how to gain head-mounted access to the bloodstream to easily combine recording and/or manipulation of neuronal activity with the reliable delivery of pharmacological agents.

  • Compared with other drug delivery methods, the intravenous technique explored here eliminates the stress and pain caused by needle pokes. The surgical and postoperative guidance provided in the protocol improves animal survival and catheter patency, increasing the reliability and reproducibility of results.

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Fig. 1: Catheter construction.
Fig. 2: Features of forceps to consider based on the task.
Fig. 3: Critical surgical steps.
Fig. 4: Sample data obtained from intravenous infusions during behavior and neural recordings.

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Data availability

All data supporting this protocol are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by National Institutes of Health grants (1R01DA042889, 1R01MH123246), Tobacco-Related Disease Research Program (26IP-0035, T32IR5075), Rita Allen Foundation, Weill Neurohub, One Mind Foundation (047483), NARSAD Young Investigator Award (23543), Brain Research Foundation (BRFSG-2015-7) and Wayne and Gladys Valley Foundation (all to S.L.). S.L. is a Weill Neurohub Investigator, John P. Stock Faculty Fellow and Rita Allen Scholar. C.L. was supported by the NSF Graduate Research Fellowship Program, Search for Hidden Figures Scholarship, UCSF IRACDA Scholars Program and HHMI Gilliam Fellowship. We thank 3rd & Gilman Studios for providing equipment to film the supplementary videos, A. Tose for analysis of fiber photometry recordings, J. M. McIntosh for providing the ArIB antagonist for intrabrain infusions and A. Gordon-Fennell for testing the protocol and providing additional insights to improve the procedure.

Author information

Authors and Affiliations

  1. Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA

    Christine Liu, Daniel J. Freeman & Stephan Lammel

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  1. Christine Liu
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  2. Daniel J. Freeman
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Contributions

C.L. designed the protocol, carried out the in vivo experiments, analysis and figure preparation, and wrote the manuscript. D.J.F. performed video documentation and assisted with the figure preparation. S.L. supervised experiments, gave conceptual support, provided funding and assisted with the manuscript preparation.

Corresponding author

Correspondence to Stephan Lammel.

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The authors declare no competing interests.

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Peer review information

Nature Protocols thanks Tommaso Patriarchi, Lauren Slosky and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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Related links

Key reference using this protocol

Liu, C. et al. Neuron 110, 3018–3035.e7 (2022): https://doi.org/10.1016/j.neuron.2022.07.003

Supplementary information

Supplementary Information

Supplementary Fig. 1

Supplementary Video 1

Making catheters. Construction of custom-made catheters and catheter caps.

Supplementary Video 2

Surgical procedure. Demonstration of key steps during the surgical procedure for the implantation of a jugular vein catheter and the mounting of the vascular access point on the skull.

Supplementary Video 3

Postoperative care. Demonstration of gentle restraint of an animal by hand or with screws on a running wheel for flushing the implanted jugular vein catheter via the head-mounted vascular access point.

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Liu, C., Freeman, D.J. & Lammel, S. Head-mounted central venous access during optical recordings and manipulations of neural activity in mice. Nat Protoc 19, 960–983 (2024). https://doi.org/10.1038/s41596-023-00928-2

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