Bold claims for optogenetics

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Abstract

Arising from J. H. Lee et al. Nature 465, 788–792 (2010)10.1038/nature09108; Lee et al. reply

In a recent Letter to Nature, Lee and colleagues1 combined optogenetic stimulation with functional magnetic resonance imaging (ofMRI) to examine the relationship between pyramidal-cell spiking and the blood oxygenation level dependent (BOLD) signal. To do so, they injected an adeno-associated viral vector into the primary motor cortex (M1) of adult rats to drive the expression of channelrhodopsin (ChR2) in cortical projection neurons, thus making them sensitive to light1. The authors then used combined light stimulation and functional magnetic resonance imaging (fMRI) to examine the effects of selective activation of the light-sensitive pyramidal cells on the BOLD signal, as well as to probe the value of this methodology for mapping brain connectivity. They found that excitation of these neurons induced positive BOLD signals both in the injected M1 region and in remote target thalamic nuclei receiving direct projections from that region, and concluded that ofMRI reliably links positive BOLD signals with increased local neuronal excitation. However, their analysis neglects the almost immediate activation of other circuits that could lead to the generation of BOLD signals through local perisynaptic rather than spiking activity. Their experiments therefore do not pin down the identity of the specific neuronal signals that give rise to the BOLD signal.

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References

  1. 1

    Lee, J. H. et al. Global and local fMRI signals driven by neurons defined optogenetically by type and wiring. Nature 465, 788–792 (2010)

  2. 2

    Douglas, R. J. & Martin, K. A. C. Recurrent neuronal circuits in the neocortex. Curr. Biol. 17, R496–R500 (2007)

  3. 3

    Markram, H. et al. Interneurons of the neocortical inhibitory system. Nature Rev. Neurosci. 5, 793–807 (2004)

  4. 4

    Somogyi, P., Tamas, G., Lujan, R. & Buhl, E. H. Salient features of synaptic organisation in the cerebral cortex. Brain Res. Brain Res. Rev. 26, 113–135 (1998)

  5. 5

    Douglas, R. J., Martin, K. A. & Whitteridge, D. An intracellular analysis of the visual responses of neurones in cat visual cortex. J. Physiol. 440, 659–696 (1991)

  6. 6

    Keller, A. Intrinsic synaptic organization of the motor cortex. Cereb. Cortex 3, 430–441 (1993)

  7. 7

    Sohal, V. S., Zhang, F., Yizhar, O. & Deisseroth, K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459, 698–702 (2009)

  8. 8

    Cardin, J. A. et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459, 663–667 (2009)

  9. 9

    Han, X. et al. Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain. Neuron 62, 191–198 (2009)

  10. 10

    Jueptner, M. & Weiller, C. Review: does measurement of regional cerebral blood flow reflect synaptic activity? Implications for PET and fMRI. Neuroimage 2, 148–156 (1995)

  11. 11

    Phillips, C. G. Actions of antidromic pyramidal volleys on single Betz cells in the cat. Q. J. Exp. Physiol. Cogn. Med. Sci. 44, 1–25 (1959)

  12. 12

    Ferster, D. & Lindstrom, S. Synaptic excitation of neurones in area 17 of the cat by intracortical axon collaterals of cortico-geniculate cells. J. Physiol. 367, 233–252 (1985)

  13. 13

    Okun, M. & Lampl, I. Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities. Nature Neurosci. 11, 535–537 (2008)

  14. 14

    Logothetis, N. K. & Wandell, B. A. Interpreting the BOLD signal. Annu. Rev. Physiol. 66, 735–769 (2004)

  15. 15

    Logothetis, N. K. What we can do and what we cannot do with fMRI. Nature 453, 869–878 (2008)

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Logothetis, N. Bold claims for optogenetics. Nature 468, E3–E4 (2010) doi:10.1038/nature09532

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