Electrophysiological Approaches for Studying Neuronal Circuits In Vivo

  • George Dragoi
Part of the Neuromethods book series (NM, volume 67)


Most of our understanding of the brain activity and its relation to behavior comes from the electrophysiological studies of neuronal activity at different levels. Extracellular recording of spiking and local field potential activity gives the most comprehensive picture of the brain activity at the neuronal ensemble level within a region as well as across brain areas. Juxtacellular recording approach is best suited for investigating the activity of individual classes of neurons that are further characterized in relation to their morphology, molecular content, and axonal projection profile. Intracellular recordings uncover intrinsic and synaptic subthreshold dynamics of individual neurons that are not detectible using the other two techniques. Electrical and optical stimulation of neurons complements the recording techniques and are used to artificially control the neuronal activity with incredibly high temporal resolution. The current work reviews these four approaches for studying neuronal activity in vivo and provides an overview of the most recent advances and trends in this field.

Key words

Local field potential Juxtacellular recordings Intracellular recordings Electrical stimulation Optogenetics 


  1. 1.
    Lee AK, Manns ID, Sakmann B et al (2006) Whole-cell recordings in freely moving rats. Neuron 51(4):399–407PubMedCrossRefGoogle Scholar
  2. 2.
    Harvey CD, Collman F, Dombeck DA et al (2009) Intracellular dynamics of hippocampal place cells during virtual navigation. Nature 461(7266):941–946PubMedCrossRefGoogle Scholar
  3. 3.
    Henze DA, Borhegyi Z, Csicsvari J et al (2000) Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J Neurophysiol 84(1):390–400PubMedGoogle Scholar
  4. 4.
    O’Keefe J, Dostrovsky J (1971) The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res 34(1):171–175PubMedCrossRefGoogle Scholar
  5. 5.
    Hubel DH, Wiesel TN (1959) Receptive fields of single neurones in the cat’s striate cortex. J Physiol 148:574–591PubMedGoogle Scholar
  6. 6.
    Gross CG, Rocha-Miranda CE, Bender DB (1972) Visual properties of neurons in inferotemporal cortex of the Macaque. J Neurophysiol 35(1):96–111PubMedGoogle Scholar
  7. 7.
    Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275(5306):1593–1599PubMedCrossRefGoogle Scholar
  8. 8.
    Gray CM, Maldonado PE, Wilson M et al (1995) Tetrodes markedly improve the reliability and yield of multiple single-unit isolation from multi-unit recordings in cat striate cortex. J Neurosci Methods 63(1–2):43–54PubMedCrossRefGoogle Scholar
  9. 9.
    Bartho P, Hirase H, Monconduit L et al (2004) Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. J Neurophysiol 92(1):600–608PubMedCrossRefGoogle Scholar
  10. 10.
    Kloosterman F, Davidson TJ, Gomperts SN et al (2009) Micro-drive array for chronic in vivo recording: drive fabrication. J Vis Exp (26). pii: 1094. doi: 10.3791/1094Google Scholar
  11. 11.
    Wilson MA, McNaughton BL (1993) Dynamics of the hippocampal ensemble code for space. Science 261(5124):1055–1058PubMedCrossRefGoogle Scholar
  12. 12.
    Siapas AG, Wilson MA (1998) Coordinated interactions between hippocampal ripples and cortical spindles during slow-wave sleep. Neuron 21(5):1123–1128PubMedCrossRefGoogle Scholar
  13. 13.
    Lee AK, Wilson MA (2002) Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36(6):1183–1194PubMedCrossRefGoogle Scholar
  14. 14.
    Ji D, Wilson MA (2007) Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat Neurosci 10(1):100–107PubMedCrossRefGoogle Scholar
  15. 15.
    Harris KD, Csicsvari J, Hirase H et al (2003) Organization of cell assemblies in the hippocampus. Nature 424(6948):552–556PubMedCrossRefGoogle Scholar
  16. 16.
    Harris KD, Henze DA, Csicsvari J (2000) Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements. J Neurophysiol 84(1):401–414PubMedGoogle Scholar
  17. 17.
    Schmitzer-Torbert N, Jackson J, Henze D et al (2005) Quantitative measures of cluster quality for use in extracellular recordings. Neuroscience 131(1):1–11PubMedCrossRefGoogle Scholar
  18. 18.
    O’Keefe J, Recce ML (1993) Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3(3):317–330PubMedCrossRefGoogle Scholar
  19. 19.
    Csicsvari J, Henze DA, Jamieson B et al (2003) Massively parallel recording of unit and local field potentials with silicon-based electrodes. J Neurophysiol 90(2):1314–1323PubMedCrossRefGoogle Scholar
  20. 20.
    Buzsaki G, Buhl DL, Harris KD et al (2003) Hippocampal network patterns of activity in the mouse. Neuroscience 116(1):201–211PubMedCrossRefGoogle Scholar
  21. 21.
    Kocsis B, Bragin A, Buzsaki G (1999) Interdependence of multiple theta generators in the hippocampus: a partial coherence analysis. J Neurosci 19(14):6200–6212PubMedGoogle Scholar
  22. 22.
    Csicsvari J, Jamieson B, Wise KD et al (2003) Mechanisms of gamma oscillations in the hippocampus of the behaving rat. Neuron 37(2):311–322PubMedCrossRefGoogle Scholar
  23. 23.
    Buzsaki G, Horvath Z, Urioste R et al (1992) High-frequency network oscillation in the hippocampus. Science 256(5059):1025–1027PubMedCrossRefGoogle Scholar
  24. 24.
    Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232(2):331–356PubMedGoogle Scholar
  25. 25.
    Moser EI, Krobert KA, Moser MB et al (1998) Impaired spatial learning after saturation of long-term potentiation. Science 281(5385):2038–2042PubMedCrossRefGoogle Scholar
  26. 26.
    Dragoi G, Harris KD, Buzsaki G (2003) Place representation within hippocampal networks is modified by long-term potentiation. Neuron 39(5):843–853PubMedCrossRefGoogle Scholar
  27. 27.
    Buzsaki G, Hsu M, Horvath Z et al (1992) Kindling-induced changes of protein kinase C levels in hippocampus and neocortex. Epilepsy Res Suppl 9:279–283PubMedGoogle Scholar
  28. 28.
    Tepper JM, Martin LP, Anderson DR (1995) GABAA receptor-mediated inhibition of rat substantia nigra dopaminergic neurons by pars reticulata projection neurons. J Neurosci 15(4):3092–3103PubMedGoogle Scholar
  29. 29.
    Deisseroth K (2011) Optogenetics. Nat Methods 8(1):26–29PubMedCrossRefGoogle Scholar
  30. 30.
    Boyden ES, Zhang F, Bamberg E et al (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9):1263–1268PubMedCrossRefGoogle Scholar
  31. 31.
    Zhao S, Cunha C, Zhang F et al (2008) Improved expression of halorhodopsin for light-induced silencing of neuronal activity. Brain Cell Biol 36(1–4):141–154PubMedCrossRefGoogle Scholar
  32. 32.
    Niessing J, Ebisch B, Schmidt KE et al (2005) Hemodynamic signals correlate tightly with synchronized gamma oscillations. Science 309(5736):948–951PubMedCrossRefGoogle Scholar
  33. 33.
    Logothetis NK, Pauls J, Augath M et al (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature 412(6843):150–157PubMedCrossRefGoogle Scholar
  34. 34.
    Tsai HC, Zhang F, Adamantidis A et al (2009) Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science 324(5930):1080–1084PubMedCrossRefGoogle Scholar
  35. 35.
    Szuts TA, Fadeyev V, Kachiguine S et al (2011) A wireless multi-channel neural amplifier for freely moving animals. Nat Neurosci 14(2):263–269PubMedCrossRefGoogle Scholar
  36. 36.
    Pinault D (1996) A novel single-cell staining procedure performed in vivo under electrophysiological control: morpho-functional features of juxtacellularly labeled thalamic cells and other central neurons with biocytin or Neurobiotin. J Neurosci Methods 65(2):113–136PubMedCrossRefGoogle Scholar
  37. 37.
    Duque A, Balatoni B, Detari L et al (2000) EEG correlation of the discharge properties of identified neurons in the basal forebrain. J Neurophysiol 84(3):1627–1635PubMedGoogle Scholar
  38. 38.
    Isomura Y, Harukuni R, Takekawa T et al (2009) Microcircuitry coordination of cortical motor information in self-initiation of voluntary movements. Nat Neurosci 12(12):1586–1593PubMedCrossRefGoogle Scholar
  39. 39.
    Ylinen A, Bragin A, Nadasdy Z et al (1995) Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms. J Neurosci 15(1 Pt 1):30–46PubMedGoogle Scholar
  40. 40.
    Foster DJ, Wilson MA (2006) Reverse replay of behavioural sequences in hippocampal place cells during the awake state. Nature 440(7084):680–683PubMedCrossRefGoogle Scholar
  41. 41.
    Zhang K, Ginzburg I, McNaughton BL et al (1998) Interpreting neuronal population activity by reconstruction: unified framework with application to hippocampal place cells. J Neurophysiol 79(2):1017–1044PubMedGoogle Scholar
  42. 42.
    Davidson TJ, Kloosterman F, Wilson MA (2009) Hippocampal replay of extended experience. Neuron 63(4):497–507PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • George Dragoi
    • 1
  1. 1.Picower Institute for Learning and MemoryMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations