Abstract
The patch-clamp technique and the whole-cell measurements derived from it have greatly advanced our understanding of the coding properties of individual neurons by allowing for a detailed analysis of their excitatory/inhibitory synaptic inputs, intrinsic electrical properties, and morphology. Because such measurements require a high level of mechanical stability they have for a long time been limited to in vitro and anesthetized preparations. Recently, however, a considerable amount of effort has been devoted to extending these techniques to awake restrained/head-fixed preparations allowing for the study of the input–output functions of neurons during behavior. In this chapter we describe a technique extending patch-clamp recordings to awake animals free to explore their environments.
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References
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100
Pei X, Volgushev M, Vidyasagar TR, Creutzfeldt OD (1991) Whole cell recording and conductance measurements in cat visual cortex in-vivo. Neuroreport 2:485–488
Ferster D, Jagadeesh B (1992) EPSP-IPSP interactions in cat visual cortex studied with in vivo whole-cell patch recording. J Neurosci 12:1262–1274
Borg-Graham L, Monier C, Fregnac Y (1996) Voltage-clamp measurement of visually-evoked conductances with whole-cell patch recordings in primary visual cortex. J Physiol Paris 90: 185–188
Margrie TW, Brecht M, Sakmann B (2002) In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflugers Arch 444:491–498
Wehr M, Zador AM (2003) Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426:442–446
Bruno RM, Sakmann B (2006) Cortex is driven by weak but synchronously active thalamocortical synapses. Science 312:1622–1627
Covey E, Kauer JA, Casseday JH (1996) Whole-cell patch-clamp recording reveals subthreshold sound-evoked postsynaptic currents in the inferior colliculus of awake bats. J Neurosci 16:3009–3018
Aksay E, Gamkrelidze G, Seung HS, Baker R, Tank DW (2001) In vivo intracellular recording and perturbation of persistent activity in a neural integrator. Nat Neurosci 4:184–193
Wilson RI, Turner GC, Laurent G (2004) Transformation of olfactory representations in the Drosophila antennal lobe. Science 303: 366–370
Crochet S, Petersen CC (2006) Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nat Neurosci 9: 608–610
Harvey CD, Collman F, Dombeck DA, Tank DW (2009) Intracellular dynamics of hippocampal place cells during virtual navigation. Nature 461:941–946
Maimon G, Straw AD, Dickinson MH (2010) Active flight increases the gain of visual motion processing in Drosophila. Nat Neurosci 13: 393–399
Domnisoru C, Kinkhabwala AA, Tank DW (2013) Membrane potential dynamics of grid cells. Nature 495:199–204
Schmidt-Hieber C, Häusser M (2013) Cellular mechanisms of spatial navigation in the medial entorhinal cortex. Nat Neurosci 16: 325–331
Haider B, Häusser M, Carandini M (2013) Inhibition dominates sensory responses in the awake cortex. Nature 493:97–100
Long MA, Lee AK (2012) Intracellular recording in behaving animals. Curr Opin Neurobiol 22:34–44
Margrie TW, Meyer AH, Caputi A, Monyer H, Hasan MT, Schaefer AT, Denk W, Brecht M (2003) Targeted whole-cell recordings in the mammalian brain in vivo. Neuron 39: 911–918
Gentet LJ, Avermann M, Matyas F, Staiger JF, Petersen CC (2010) Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice. Neuron 65:422–435
Polack PO, Friedman J, Golshani P (2013) Cellular mechanisms of brain state-dependent gain modulation in visual cortex. Nat Neurosci 16:1331–1339
Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412
Hölscher C, Schnee A, Dahmen H, Setia L, Mallot HA (2005) Rats are able to navigate in virtual environments. J Exp Biol 208: 561–569
Chen G, King JA, Burgess N, O’Keefe J (2013) How vision and movement combine in the hippocampal place code. Proc Natl Acad Sci U S A 110:378–383
Ravassard P, Kees A, Willers B, Ho D, Aharoni D, Cushman J, Aghajan ZM, Mehta MR (2013) Multisensory control of hippocampal spatiotemporal selectivity. Science 340: 1342–1346
Lee AK, Manns ID, Sakmann B, Brecht M (2006) Whole-cell recordings in freely moving rats. Neuron 51:399–407
Lee AK, Epsztein J, Brecht M (2009) Head-anchored whole-cell recordings in freely moving rats. Nat Protoc 4:385–392
Lee AK, Epsztein J, Brecht M (2008) Whole-cell recordings of hippocampal CA1 place cell activity in freely moving rats. Soc Neurosci Abstr 690:21
Epsztein J, Lee AK, Brecht M (2010) Impact of spikelets on hippocampal CA1 pyramidal cell activity during spatial exploration. Science 327:474–477
Epsztein J, Brecht M, Lee AK (2011) Intracellular determinants of hippocampal CA1 place and silent cell activity in a novel environment. Neuron 70:109–120
Lee D, Lin BJ, Lee AK (2012) Hippocampal place fields emerge upon single-cell manipulation of excitability during behavior. Science 337:849–853
Long MA, Jin DZ, Fee MS (2010) Support for a synaptic chain model of neuronal sequence generation. Nature 468:394–399
Horikawa K, Armstrong WE (1988) A versatile means of intracellular labeling: injection of biocytin and its detection with avidin conjugates. J Neurosci Methods 25:1–11
Acknowledgments
This work was supported by an EMBO Long Term Fellowship and HHMI (to A. K. L.); a Human Frontier Science Program Long Term Fellowship, INSERM, Agence Nationale de la Recherche (grant ANR-09-BLAN-0259-01 and ANR-10-R11014AA), Région PACA (project EPIVIRT), A*MIDEX project (ANR-11-IDEX-0001-02) funded by the «Investissements d’Avenir» French Government program (to J.E.); Humboldt Universität zu Berlin, the Bernstein Center for Computational Neuroscience Berlin, the German Federal Ministry of Education and Research (BMBF, Förderkennzeichen 01GQ1001A), NeuroCure, a European Research Council grant, and the Gottfried Wilhelm Leibniz Prize of the DFG (to M.B).
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Lee, A.K., Epsztein, J., Brecht, M. (2014). Whole-Cell Patch-Clamp Recordings in Freely Moving Animals. In: Martina, M., Taverna, S. (eds) Patch-Clamp Methods and Protocols. Methods in Molecular Biology, vol 1183. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1096-0_17
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DOI: https://doi.org/10.1007/978-1-4939-1096-0_17
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