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Head-anchored whole-cell recordings in freely moving rats

Nature Protocols volume 4, pages 385–392 (2009)Cite this article

Abstract

Intracellular recordings are routinely used to study the synaptic and intrinsic properties of neurons in vitro. A key requirement for these recordings is a mechanically very stable preparation; thus their use in vivo had been limited previously to head-restrained animals. We have recently demonstrated that anchoring the electrode rigidly in place with respect to the skull provides sufficient stabilization for long-lasting, high-quality whole-cell recordings in awake, freely moving rats. This protocol describes our procedure in detail, adds specific instructions for targeting hippocampal CA1 pyramidal neurons and updates it with changes that facilitate patching and improve the success rate. The changes involve combining a standard, nonhead-mounted micromanipulator with a gripper to firmly hold the recording pipette during the anchoring process then gently release it afterwards. The procedure from the beginning of surgery to the end of a recording takes ∼5 h. This technique allows new studies of the mechanisms underlying neuronal integration and cellular/synaptic plasticity in identified cells during natural behaviors.

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Figure 1: Overview of the experimental setup.
Figure 2: Arrangement of head-mounted and non–head-mounted equipment.
Figure 3: Anchoring process.
Figure 4: Whole-cell recordings of hippocampal neurons in freely moving rats.

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Acknowledgements

We are grateful for the technical contributions of J. Gassmann at Gassmann Engineering; E. Zech at ABIMEK; A. Brouwer at the Erasmus MC Department of Experimental Medical Instrumentation; and R. Karpinski, B. Geue and A. Stern at Humboldt University. We also thank J. Schiller for recommendations on pipette tip shape and A. Kim for helpful discussions on anesthesia. This work was supported by the Bernstein Center for Computational Neuroscience, Neurocure, a European Molecular Biology Organization Long-Term Fellowship to A.K.L. and a Human Frontier Science Program Long-Term Fellowship to J.E.

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Author notes

  1. Albert K Lee

    Present address: Present address: Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, Virginia 20147, USA.,

  2. Jérôme Epsztein

    Present address: Present address: Institut de Neurobiologie de la Méditerranée, Institut National de la Santé et de la Recherche Médicale U901, Parc Scientifique et Technologique de Luminy, 163 Route de Luminy, 13273 Marseille, Cedex 09, France.,

  3. Albert K Lee and Jérôme Epsztein: These authors contributed equally to this work.

Authors and Affiliations

  1. Bernstein Center for Computational Neuroscience, Humboldt University, Philippstr. 13, House 6, Berlin, 10115, Germany

    Albert K Lee, Jérôme Epsztein & Michael Brecht

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  1. Albert K Lee
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Correspondence to Albert K Lee, Jérôme Epsztein or Michael Brecht.

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Lee, A., Epsztein, J. & Brecht, M. Head-anchored whole-cell recordings in freely moving rats. Nat Protoc 4, 385–392 (2009). https://doi.org/10.1038/nprot.2009.5

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