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Acetylcholine contributes through muscarinic receptors to attentional modulation in V1

Abstract

Attention exerts a strong influence over neuronal processing in cortical areas1,2. It selectively increases firing rates2,3,4 and affects tuning properties1,5, including changing receptive field locations and sizes3,6. Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca mulatta) performed a task that demanded top-down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1.

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Figure 1: Drug effects on attentional modulation.
Figure 2: Acetylcholine effects on attentional modulation.
Figure 3: Effect of the muscarinic antagonist scopolamine on attentional modulation.
Figure 4: Effect of the nicotinic antagonist mecamylamine on attentional modulation.

References

  1. 1

    Spitzer, H., Desimone, R. & Moran, J. Increased attention enhances both behavioral and neuronal performance. Science 240, 338–340 (1988)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Treue, S. & Maunsell, J. H. R. Attentional modulation of visual motion processing in cortical areas MT and MST. Nature 382, 539–541 (1996)

    ADS  CAS  Article  Google Scholar 

  3. 3

    Reynolds, J. H., Chelazzi, L. & Desimone, R. Competitive mechanisms subserve attention in macaque areas V2 and V4. J. Neurosci. 19, 1736–1753 (1999)

    CAS  Article  Google Scholar 

  4. 4

    Roelfsema, P. R., Lamme, V. A. & Spekreijse, H. Object-based attention in the primary visual cortex of the macaque monkey. Nature 395, 376–381 (1998)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Roberts, M., Delicato, L. S., Herrero, J., Gieselmann, M. A. & Thiele, A. Attention alters spatial integration in macaque V1 in an eccentricity-dependent manner. Nature Neurosci. 10, 1483–1491 (2007)

    CAS  Article  Google Scholar 

  6. 6

    Womelsdorf, T., Anton-Erxleben, K., Pieper, F. & Treue, S. Dynamic shifts of visual receptive fields in cortical area MT by spatial attention. Nature Neurosci. 9, 1156–1160 (2006)

    CAS  Article  Google Scholar 

  7. 7

    Corbetta, M. & Shulman, G. L. Control of goal-directed and stimulus-driven attention in the brain. Nature Rev. Neurosci. 3, 201–215 (2002)

    CAS  Article  Google Scholar 

  8. 8

    Moore, T. & Armstrong, K. M. Selective gating of visual signals by microstimulation of frontal cortex. Nature 421, 370–373 (2003)

    ADS  CAS  Article  Google Scholar 

  9. 9

    Russchen, F. T., Amaral, D. G. & Price, J. L. The afferent connections of the substantia innominata in the monkey, Macaca fascicularis . J. Comp. Neurol. 242, 1–27 (1985)

    CAS  Article  Google Scholar 

  10. 10

    Sarter, M., Hasselmo, M. E., Bruno, J. P. & Givens, B. Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Res. Rev. 48, 98–111 (2005)

    CAS  Article  Google Scholar 

  11. 11

    Furey, M. L., Pietrini, P., Haxby, J. V. & Drevets, W. C. Selective effects of cholinergic modulation on task performance during selective attention. Neuropsychopharmacology 33, 913–923 (2008)

    CAS  Article  Google Scholar 

  12. 12

    Robbins, T. W. Chemistry of the mind: neurochemical modulation of prefrontal cortical function. J. Comp. Neurol. 493, 140–146 (2005)

    CAS  Article  Google Scholar 

  13. 13

    Parikh, V., Kozak, R., Martinez, V. & Sarter, M. Prefrontal acetylcholine release controls cue detection on multiple timescales. Neuron 56, 141–154 (2007)

    CAS  Article  Google Scholar 

  14. 14

    Nelson, C. L., Sarter, M. & Bruno, J. P. Prefrontal cortical modulation of acetylcholine release in posterior parietal cortex. Neuroscience 132, 347–359 (2005)

    CAS  Article  Google Scholar 

  15. 15

    McGaughy, J., Dalley, J. W., Morrison, C. H., Everitt, B. J. & Robbins, T. W. Selective behavioral and neurochemical effects of cholinergic lesions produced by intrabasalis infusions of 192 IgG-saporin on attentional performance in a five-choice serial reaction time task. J. Neurosci. 22, 1905–1913 (2002)

    CAS  Article  Google Scholar 

  16. 16

    Nobili, L. & Sannita, W. G. Cholinergic modulation, visual function and Alzheimer’s dementia. Vision Res. 37, 3559–3571 (1997)

    CAS  Article  Google Scholar 

  17. 17

    Thiele, A., Delicato, L. S., Roberts, M. J. & Gieselmann, M. A. A novel electrode-pipette design for simultaneous recording of extracellular spikes and iontophoretic drug application in awake behaving monkeys. J. Neurosci. Methods 158, 207–211 (2006)

    CAS  Article  Google Scholar 

  18. 18

    Reynolds, J. H., Pasternak, T. & Desimone, R. Attention increases sensitivity of V4 neurons. Neuron 26, 703–714 (2000)

    CAS  Article  Google Scholar 

  19. 19

    Goldman-Rakic, P. S., Muly, E. C. & Williams, G. V. D1 receptors in prefrontal cells and circuits. Brain Res. Rev. 31, 295–301 (2000)

    CAS  Article  Google Scholar 

  20. 20

    Witte, E. A., Davidson, M. C. & Marrocco, R. T. Effects of altering brain cholinergic activity on covert orienting of attention: comparison of monkey and human performance. Psychopharmacology (Berl.) 132, 324–334 (1997)

    CAS  Article  Google Scholar 

  21. 21

    Davidson, M. C. & Marrocco, R. T. Local infusion of scopolamine into intraparietal cortex slows covert orienting in rhesus monkeys. J. Neurophysiol. 83, 1536–1549 (2000)

    CAS  Article  Google Scholar 

  22. 22

    Disney, A. A., Domakonda, K. V. & Aoki, C. Differential expression of muscarinic acetylcholine receptors across excitatory and inhibitory cells in visual cortical areas V1 and V2 of the macaque monkey. J. Comp. Neurol. 499, 49–63 (2006)

    CAS  Article  Google Scholar 

  23. 23

    Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560–1563 (2001)

    ADS  CAS  Article  Google Scholar 

  24. 24

    Luck, S. J., Chelazzi, L., Hillyard, S. A. & Desimone, R. Neural mechanisms of spatial selective attention in areas V1, V2, and V4 of macaque visual cortex. J. Neurophysiol. 77, 24–42 (1997)

    CAS  Article  Google Scholar 

  25. 25

    Disney, A. A., Aoki, C. & Hawken, M. J. Gain modulation by nicotine in macaque V1. Neuron 56, 701–713 (2007)

    CAS  Article  Google Scholar 

  26. 26

    McAdams, C. J. & Reid, R. C. Attention modulates the responses of simple cells in monkey primary visual cortex. J. Neurosci. 25, 11023–11033 (2005)

    CAS  Article  Google Scholar 

  27. 27

    Thiel, C. M., Zilles, K. & Fink, G. R. Nicotine modulates reorienting of visuospatial attention and neural activity in human parietal cortex. Neuropsychopharmacology 30, 810–820 (2005)

    CAS  Article  Google Scholar 

  28. 28

    Yu, A. J. & Dayan, P. Uncertainty, neuromodulation, and attention. Neuron 46, 681–692 (2005)

    CAS  Article  Google Scholar 

  29. 29

    Fournier, G. N., Semba, K. & Rasmusson, D. D. Modality- and region-specific acetylcholine release in the rat neocortex. Neuroscience 126, 257–262 (2004)

    CAS  Article  Google Scholar 

  30. 30

    von Engelhardt, J., Eliava, M., Meyer, A. H., Rozov, A. & Monyer, H. Functional characterization of intrinsic cholinergic interneurons in the cortex. J. Neurosci. 27, 5633–5642 (2007)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The work was supported by the BBSRC (BBS/B/09325), the Wellcome Trust (070380/Z/03/Z) and the Gatsby Charitable Foundation.

Author Contributions J.L.H., M.J.R., L.S.D. and M.A.G. performed the experimental work; A.T. and P.D. did the project planning; A.T., J.L.H. and M.J.R. did the data analysis; A.T. and P.D. wrote the manuscript.

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Correspondence to A. Thiele.

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Herrero, J., Roberts, M., Delicato, L. et al. Acetylcholine contributes through muscarinic receptors to attentional modulation in V1. Nature 454, 1110–1114 (2008). https://doi.org/10.1038/nature07141

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