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Imaging the Dynamics of Neocortical Population Activity in Behaving and Freely Moving Mammals

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Membrane Potential Imaging in the Nervous System and Heart

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 859))

Abstract

The development of functional imaging techniques applicable to neuroscience and covering a wide range of spatial and temporal scales has greatly facilitated the exploration of the relationships between cognition, behaviour and electrical brain activity. For mammals, the neocortex plays a particularly profound role in generating sensory perception, controlling voluntary movement, higher cognitive functions and planning goal-directed behaviours. Since these remarkable functions of the neocortex cannot be explored in simple model preparations or in anesthetised animals, the neural basis of behaviour must be explored in awake behaving subjects. Because neocortical function is highly distributed across many rapidly interacting regions, it is essential to measure spatiotemporal dynamics of cortical activity in real-time. Extensive work in anesthetised mammals has shown that in vivo Voltage-Sensitive Dye Imaging (VSDI) reveals the neocortical population membrane potential dynamics at millisecond temporal resolution and subcolumnar spatial resolution. Here, we describe recent advances indicating that VSDI is also already well-developed for exploring cortical function in behaving monkeys and mice. The first animal model, the non-human primate, is well-suited for fundamental exploration of higher-level cognitive function and behavior. The second animal model, the mouse, benefits from a rich arsenal of molecular and genetic technologies. In the monkey, imaging from the same patch of cortex, repeatedly, is feasible for a long period of time, up to a year. In the rodent, VSDI is applicable to freely moving and awake head-restrained mice. Interactions between different cortical areas and different cortical columns can therefore now be dynamically mapped through VSDI and related to the corresponding behaviour. Thus by applying VSDI to mice and monkeys one can begin to explore how behaviour emerges from neuronal activity in neuronal networks residing in different cortical areas.

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References

  • Akemann W, Mutoh H, Perron A, Rossier J, Kn­pfel T (2010) Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins. Nat Methods 7:643–649

    Google Scholar 

  • Arieli A, Grinvald A (2002) Combined optical imaging and targeted electrophysiological manipulations in anesthetized and behaving animals. J Neurosci Methods 116:15–28

    Article  PubMed  Google Scholar 

  • Arieli A, Shoham D, Hildesheim R, Grinvald A (1995) Coherent spatio-temporal pattern of on-going activity revealed by real time optical imaging coupled with single unit recording in the cat visual cortex. J Neurophysiol 73:2072–2093

    CAS  PubMed  Google Scholar 

  • Arieli A, Sterkin A, Grinvald A, Aertsen A (1996) Dynamics of ongoing activity: explanation of the large variability in evoked cortical responses. Science 273:1868–1871

    Article  CAS  PubMed  Google Scholar 

  • Arieli A, Grinvald A, Slovin H (2002) Dural substitute for longterm imaging of cortical activity in behaving monkeys and its clinical implications. J Neurosci Methods 114:119–133

    Article  PubMed  Google Scholar 

  • Ataka K, Pieribone VA (2002) A genetically targetable fluorescent probe of channel gating with rapid kinetics. Biophys J 82:509–516

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Berger T, Borgdorff AJ et al (2007) Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex. J Neurophysiol 97:3751–3762

    Article  CAS  PubMed  Google Scholar 

  • Chakrabarti S, Alloway KD (2006) Differential origin of projections from SI barrel cortex to the whisker representations in SII and MI. J Comp Neurol 498:624–636

    Article  PubMed  Google Scholar 

  • Cohen MR, Newsome WT (2004) What electrical microstimulation has revealed about the neural basis of cognition. Curr Opin Neurobiol 14:169–177

    Article  CAS  PubMed  Google Scholar 

  • Crochet S, Petersen CCH (2006) Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nat Neurosci 9:608–610

    Article  CAS  PubMed  Google Scholar 

  • Denk W, Strickler JH, Webb WW (1990) Two-photon laser scanning fluorescence microscopy. Science 248:73–76

    Article  CAS  PubMed  Google Scholar 

  • Derdikman D, Hildesheim R, Ahissar E, Arieli A, Grinvald A (2003) Imaging spatiotemporal dynamics of surround inhibition in the barrels somatosensory cortex. J Neurosci 23:3100–3105

    CAS  PubMed  Google Scholar 

  • Dimitrov D, He Y et al (2007) Engineering and characterization of an enhanced fluorescent protein voltage sensor. PLoS One 2, e440

    Article  PubMed Central  PubMed  Google Scholar 

  • Fekete T, Pitowsky I, Grinvald A, Omer DB (2009) The representational capacity of cortical tissue. Comput Neurosci 178:31–39

    Google Scholar 

  • Ferezou I, Bolea S, Petersen CCH (2006) Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice. Neuron 50:617–629

    Article  CAS  PubMed  Google Scholar 

  • Ferezou I, Haiss F et al (2007) Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice. Neuron 56:907–923

    Article  CAS  PubMed  Google Scholar 

  • Flusberg BA, Cocker ED et al (2005) Fiber-optic fluorescence imaging. Nat Methods 2:941–950

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Flusberg BA, Nimmerjahn A et al (2008) High-speed, miniaturized fluorescence microscopy in freely moving mice. Nat Methods 5:935–938

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Grinvald A, Hildesheim R (2004) VSDI: a new era in functional imaging of cortical dynamics. Nat Rev Neurosci 5:874–885

    Article  CAS  PubMed  Google Scholar 

  • Grinvald A, Anglister L, Freeman JA, Hildesheim R, Manker A (1984) Real-time optical imaging of naturally evoked electrical activity in intact frog brain. Nature 308:848–850

    Article  CAS  PubMed  Google Scholar 

  • Grinvald A, Lieke E, Frostig RD, Gilbert CD, Wiesel TN (1986) Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 324:361–364

    Article  CAS  PubMed  Google Scholar 

  • Grinvald A, Frostig RD et al (1989) Optical imaging of activity in the visual cortex. In: Lam D, Glibert CD (eds). MIT Press, Cambridge, MA

    Google Scholar 

  • Grinvald A, Bonhoeffer T et al (1991) Optical imaging of architecture and function in the living brain. In: Squire L (ed) Memory, organization and locus of change. Oxford University Press, Oxford

    Google Scholar 

  • Grinvald A, Shoham D et al (1999) In-vivo optical imaging of cortical architecture and dynamics. In: Windhorst U, Johansson H (eds) Modern techniques in neuroscience research. Springer, Berlin

    Google Scholar 

  • Hebb D (1949) The organization of behavior. Wiley, New York, NY

    Google Scholar 

  • Hubel DH, Wiesel TN (1962) Receptive fields, binocular interactions and functional architecture in the cat’s visual cortex. J Physiol 160:106–154

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jin L, Han Z, Platisa J, Wooltorton JR, Cohen LB, Pieribone VA (2012) Single action potentials and subthreshold electrical events imaged in neurons with a fluorescent protein voltage probe. Neuron 75:779–785

    Google Scholar 

  • Kenet T, Bibitchkov D, Tsodyks M, Grinvald A, Arieli A (2003) Spontaneously occurring cortical representations of visual attributes. Nature 425:954–956

    Article  CAS  PubMed  Google Scholar 

  • Kleinfeld D, Delaney KR (1996) Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage-sensitive dyes. J Comp Neurol 375:89–108

    Article  CAS  PubMed  Google Scholar 

  • Kralj JM, Douglass AD, Hochbaum DR, Maclaurin D, Cohen AE (2011) Optical recording of action potentials in mammalian neurons using a microbial rhodopsin. Nat Methods 9:90–95

    Google Scholar 

  • Knutsen PM, Pietr M, Ahissar E (2006) Haptic object localization in the vibrissal system: behavior and performance. J Neurosci 26:8451–8464

    Article  CAS  PubMed  Google Scholar 

  • Lampl I, Reichova I, Ferster D (1999) Synchronous membrane potential fluctuations in neurons of the cat visual cortex. Neuron 22:361–374

    Article  CAS  PubMed  Google Scholar 

  • Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature 412:150–157

    Article  CAS  PubMed  Google Scholar 

  • Lundby A, Mutoh H, Dimitrov D, Akemann W, Knöpfel T (2008) Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements. PLoS One 3, e2514

    Article  PubMed Central  PubMed  Google Scholar 

  • Madisen L, Garner AR, Shimaoka D, Chuong AS, Klapoetke NC, Li L, van der Bourg A, Niino Y, Egolf L, Monetti C, Gu H, Mills M, Cheng A, Tasic B, Nguyen TN, Sunkin SM, Benucci A, Nagy A, Miyawaki A, Helmchen F, Empson RM, Kn­pfel T, Boyden ES, Reid RC, Carandini M, Zeng H (2015) Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance. Neuron 85:942–958

    Google Scholar 

  • Mehta SB, Whitmer D, Figueroa R, Williams BA, Kleinfeld D (2007) Active spatial perception in the vibrissa scanning sensorimotor system. PLoS Biol 5, e15

    Article  PubMed Central  PubMed  Google Scholar 

  • Miyawaki A, Llopis J et al (1997) Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388:834–835

    Article  Google Scholar 

  • Mountcastle VB (1957) Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J Neurophysiol 20:408–434

    CAS  PubMed  Google Scholar 

  • Newsome WT, Britten KH, Movshon JA (1989) Neuronal correlates of a perceptual decision. Nature 341:52–54

    Article  CAS  PubMed  Google Scholar 

  • Omer DB, Grinvald A (2008) The dynamics of evoked and ongoing activity in the behaving monkey. Rev Neurosci 19:S50

    Google Scholar 

  • Orbach HS, Cohen LB, Grinvald A (1985) Optical mapping of electrical activity in rat somatosensory and visual cortex. J Neurosci 5:1886–1895

    CAS  PubMed  Google Scholar 

  • Petersen CCH (2007) The functional organization of the barrel cortex. Neuron 56:339–355

    Article  CAS  PubMed  Google Scholar 

  • Petersen CCH, Grinvald A, Sakmann B (2003a) Spatiotemporal dynamics of sensory responses in layer 2/3 of rat barrel cortex measured in vivo by voltage-sensitive dye imaging combined with whole-cell voltage recordings and neuron reconstructions. J Neurosci 23:1298–1309

    CAS  PubMed  Google Scholar 

  • Petersen CCH, Hahn TTG, Mehta M, Grinvald A, Sakmann B (2003b) Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex. Proc Natl Acad Sci U S A 100:13638–13643

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Poulet JFA, Petersen CCH (2008) Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454:881–885

    Article  CAS  PubMed  Google Scholar 

  • Ratzlaff EH, Grinvald A (1991) A tandem-lens epifluorescence macroscope: hundred-fold brightness advantage for wide-field imaging. J Neurosci Methods 36:127–137

    Article  CAS  PubMed  Google Scholar 

  • Sakai R, Repunte-Canonigo V, Raj CD, Knöpfel T (2001) Design and characterization of a DNA-encoded, voltage-sensitive fluorescent protein. Eur J Neurosci 13:2314–2318

    Article  CAS  PubMed  Google Scholar 

  • Seidemann E, Arieli A, Grinvald A, Slovin H (2002) Dynamics of depolarization and hyperpolarization in the frontal cortex and saccade goal. Science 295:862–865

    Article  CAS  PubMed  Google Scholar 

  • Shoham D, Glaser DE et al (1999) Imaging cortical dynamics at high spatial and temporal resolution with novel blue voltage-sensitive dyes. Neuron 24:791–802

    Article  CAS  PubMed  Google Scholar 

  • Siegel MS, Isacoff EY (1997) A genetically encoded optical probe of membrane voltage. Neuron 19:735–741

    Article  CAS  PubMed  Google Scholar 

  • Slovin H, Arieli A, Hildesheim R, Grinvald A (2002) Long-term voltage-sensitive dye imaging reveals cortical dynamics in behaving monkeys. J Neurophysiol 88:3421–3438

    Article  PubMed  Google Scholar 

  • Slovin H, Strick PL, Hildesheim R, Grinvald A (2003) Voltage sensitive dye imaging in the motor cortex I. Intra- and intercortical connectivity revealed by microstimulation in the awake monkey. Soc Neurosci Abstr 554(8)

    Google Scholar 

  • Stosiek C, Garaschuk O, Holthoff K, Konnerth A (2003) In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci U S A 100:7319–7324

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Strick P, Grinvald A, Hildesheim R, Slovin H (2003) Voltage sensitive dye imaging in the motor cortex II. Cortical correlates of Go/No-Go delayed response task. Soc Neurosci Abstr 918(8)

    Google Scholar 

  • St-Pierre F, Marshall JD, Yang Y, Gong Y, Schnitzer MJ, Lin MZ (2014) High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor. Nat Neurosci 17:884-889

    Google Scholar 

  • Tehovnik EJ, Tolias AS, Sultan F, Slocum WM, Logothetis NK (2006) Direct and indirect activation of cortical neurons by electrical microstimulation. J Neurophysiol 96:512–521

    Article  CAS  PubMed  Google Scholar 

  • Trachtenberg JT, Chen BE et al (2002) Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420:788–794

    Article  CAS  PubMed  Google Scholar 

  • Tsodyks M, Kenet T, Grinvald A, Arieli A (1999) The spontaneous activity of single cortical neurons depends on the underlying global functional architecture. Science 286:1943–1946

    Article  CAS  PubMed  Google Scholar 

  • Vincent JL, Patel GH et al (2007) Intrinsic functional architecture in the anaesthetized monkey brain. Nature 447:83–86

    Article  CAS  PubMed  Google Scholar 

  • von Heimendahl M, Itskov PM, Arabzadeh E, Diamond ME (2007) Neuronal activity in rat barrel cortex underlying texture discrimination. PLoS Biol 5, e305

    Article  Google Scholar 

  • Woolsey TA, Van der Loos H (1970) The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res 17:205–242

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

AG’s research was funded by the Weizmann Institute of Science, The Grodetsky Center, the Goldsmith, Glasberg, Heineman and Korber foundations, BMBF, ISF grants, Ms. Enoch and the EU daisy grants. CCHP’s research was funded by grants from the Swiss National Science Foundation and SystemsX.ch.

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Correspondence to Carl C. H. Petersen .

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Grinvald, A., Petersen, C.C.H. (2015). Imaging the Dynamics of Neocortical Population Activity in Behaving and Freely Moving Mammals. In: Canepari, M., Zecevic, D., Bernus, O. (eds) Membrane Potential Imaging in the Nervous System and Heart. Advances in Experimental Medicine and Biology, vol 859. Springer, Cham. https://doi.org/10.1007/978-3-319-17641-3_11

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