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Basal forebrain activation enhances cortical coding of natural scenes

Abstract

The nucleus basalis of the basal forebrain is an essential component of the neuromodulatory system controlling the behavioral state of an animal and it is thought to be important in regulating arousal and attention. However, the effect of nucleus basalis activation on sensory processing remains poorly understood. Using polytrode recording in rat visual cortex, we found that nucleus basalis stimulation caused prominent decorrelation between neurons and marked improvement in the reliability of neuronal responses to natural scenes. The decorrelation depended on local activation of cortical muscarinic acetylcholine receptors, whereas the increased reliability involved distributed neural circuits, as evidenced by nucleus basalis–induced changes in thalamic responses. Further analysis showed that the decorrelation and increased reliability improved cortical representation of natural stimuli in a complementary manner. Thus, the basal forebrain neuromodulatory circuit, which is known to be activated during aroused and attentive states, acts through both local and distributed mechanisms to improve sensory coding.

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Figure 1: Effects of nucleus basalis stimulation on local field activity in V1.
Figure 2: Effect of nucleus basalis stimulation on multiunit activity throughout the depth of cortex.
Figure 3: Nucleus basalis stimulation decreases correlation between cortical neurons during visual stimulation.
Figure 4: Nucleus basalis stimulation increases the reliability of individual neurons in response to natural scenes.
Figure 5: Application of mAChR antagonist diminishes nucleus basalis-induced decorrelation, but does not affect increases in response reliability.
Figure 6: Nucleus basalis stimulation increases response reliability and shifts firing mode in the LGN.
Figure 7: Increased reliability and decreased correlation both contribute to improved coding of natural stimuli.

References

  1. Robbins, T.W. Arousal systems and attentional processes. Biol. Psychol. 45, 57–71 (1997).

    Article  CAS  Google Scholar 

  2. Jones, B.E. Modulation of cortical activation and behavioral arousal by cholinergic and orexinergic systems. Ann. NY Acad. Sci. 1129, 26–34 (2008).

    Article  CAS  Google Scholar 

  3. Berridge, C.W. & Waterhouse, B.D. The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res. Brain Res. Rev. 42, 33–84 (2003).

    Article  Google Scholar 

  4. Steriade, M. & McCarley, R.W. Brainstem Control of Wakefulness and Sleep (Plenum Press, New York, 1990).

  5. Lehmann, J., Nagy, J.I., Atmadia, S. & Fibiger, H.C. The nucleus basalis magnocellularis: the origin of a cholinergic projection to the neocortex of the rat. Neuroscience 5, 1161–1174 (1980).

    Article  CAS  Google Scholar 

  6. Everitt, B.J. & Robbins, T.W. Central cholinergic systems and cognition. Annu. Rev. Psychol. 48, 649–684 (1997).

    Article  CAS  Google Scholar 

  7. 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. Brain Res. Rev. 48, 98–111 (2005).

    Article  CAS  Google Scholar 

  8. Hasselmo, M.E. Neuromodulation and cortical function: modeling the physiological basis of behavior. Behav. Brain Res. 67, 1–27 (1995).

    Article  CAS  Google Scholar 

  9. Kilgard, M.P. & Merzenich, M.M. Cortical map reorganization enabled by nucleus basalis activity. Science 279, 1714–1718 (1998).

    Article  CAS  Google Scholar 

  10. Froemke, R.C., Merzenich, M.M. & Schreiner, C.E. A synaptic memory trace for cortical receptive field plasticity. Nature 450, 425–429 (2007).

    Article  CAS  Google Scholar 

  11. Bakin, J.S. & Weinberger, N.M. Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis. Proc. Natl. Acad. Sci. USA 93, 11219–11224 (1996).

    Article  CAS  Google Scholar 

  12. Lee, M.G., Hassani, O.K., Alonso, A. & Jones, B.E. Cholinergic basal forebrain neurons burst with theta during waking and paradoxical sleep. J. Neurosci. 25, 4365–4369 (2005).

    Article  CAS  Google Scholar 

  13. Jones, B.E. Activity, modulation and role of basal forebrain cholinergic neurons innervating the cerebral cortex. Prog. Brain Res. 145, 157–169 (2004).

    Article  CAS  Google Scholar 

  14. Laplante, F., Morin, Y., Quirion, R. & Vaucher, E. Acetylcholine release is elicited in the visual cortex, but not in the prefrontal cortex, by patterned visual stimulation: a dual in vivo microdialysis study with functional correlates in the rat brain. Neuroscience 132, 501–510 (2005).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Fiser, J., Chiu, C. & Weliky, M. Small modulation of ongoing cortical dynamics by sensory input during natural vision. Nature 431, 573–578 (2004).

    Article  CAS  Google Scholar 

  17. Tsodyks, M., Kenet, T., Grinvald, A. & Arieli, A. Linking spontaneous activity of single cortical neurons and the underlying functional architecture. Science 286, 1943–1946 (1999).

    Article  CAS  Google Scholar 

  18. Poulet, J.F. & Petersen, C.C. Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454, 881–885 (2008).

    Article  CAS  Google Scholar 

  19. Petersen, C.C., Hahn, T.T., Mehta, M., Grinvald, A. & Sakmann, B. Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex. Proc. Natl. Acad. Sci. USA 100, 13638–13643 (2003).

    Article  CAS  Google Scholar 

  20. Wörgotter, F. et al. State-dependent receptive-field restructuring in the visual cortex. Nature 396, 165–168 (1998).

    Article  Google Scholar 

  21. Metherate, R., Cox, C.L. & Ashe, J.H. Cellular bases of neocortical activation: modulation of neural oscillations by the nucleus basalis and endogenous acetylcholine. J. Neurosci. 12, 4701–4711 (1992).

    Article  CAS  Google Scholar 

  22. McCormick, D.A. Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog. Neurobiol. 39, 337–388 (1992).

    Article  CAS  Google Scholar 

  23. Xiang, Z., Huguenard, J.R. & Prince, D.A. Cholinergic switching within neocortical inhibitory networks. Science 281, 985–988 (1998).

    Article  CAS  Google Scholar 

  24. Hsieh, C.Y., Cruikshank, S.J. & Metherate, R. Differential modulation of auditory thalamocortical and intracortical synaptic transmission by cholinergic agonist. Brain Res. 880, 51–64 (2000).

    Article  CAS  Google Scholar 

  25. Gil, Z., Connors, B.W. & Amitai, Y. Differential regulation of neocortical synapses by neuromodulators and activity. Neuron 19, 679–686 (1997).

    Article  CAS  Google Scholar 

  26. Kruglikov, I. & Rudy, B. Perisomatic GABA release and thalamocortical integration onto neocortical excitatory cells are regulated by neuromodulators. Neuron 58, 911–924 (2008).

    Article  CAS  Google Scholar 

  27. Oldford, E. & Castro-Alamancos, M.A. Input-specific effects of acetylcholine on sensory and intracortical evoked responses in the “barrel cortex” in vivo. Neuroscience 117, 769–778 (2003).

    Article  CAS  Google Scholar 

  28. Bazhenov, M., Timofeev, I., Steriade, M. & Sejnowski, T.J. Model of thalamocortical slow-wave sleep oscillations and transitions to activated States. J. Neurosci. 22, 8691–8704 (2002).

    Article  CAS  Google Scholar 

  29. Castro-Alamancos, M.A. Dynamics of sensory thalamocortical synaptic networks during information processing states. Prog. Neurobiol. 74, 213–247 (2004).

    Article  Google Scholar 

  30. Disney, A.A., Aoki, C. & Hawken, M.J. Gain modulation by nicotine in macaque v1. Neuron 56, 701–713 (2007).

    Article  CAS  Google Scholar 

  31. Sillito, A.M. & Kemp, J.A. Cholinergic modulation of the functional organization of the cat visual cortex. Brain Res. 289, 143–155 (1983).

    Article  CAS  Google Scholar 

  32. Müller, C.M. & Singer, W. Acetylcholine-induced inhibition in the cat visual cortex is mediated b7 a GABAergic mechanism. Brain Res. 487, 335–342 (1989).

    Article  Google Scholar 

  33. Sato, H., Hata, Y., Masui, H. & Tsumoto, T. A functional role of cholinergic innervation to neurons in the cat visual cortex. J. Neurophysiol. 58, 765–780 (1987).

    Article  CAS  Google Scholar 

  34. Zinke, W. et al. Cholinergic modulation of response properties and orientation tuning of neurons in primary visual cortex of anaesthetized Marmoset monkeys. Eur. J. Neurosci. 24, 314–328 (2006).

    Article  CAS  Google Scholar 

  35. Herrero, J.L. et al. Acetylcholine contributes through muscarinic receptors to attentional modulation in V1. Nature 454, 1110–1114 (2008).

    Article  CAS  Google Scholar 

  36. Buzsaki, G. et al. Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J. Neurosci. 8, 4007–4026 (1988).

    Article  CAS  Google Scholar 

  37. Blanche, T.J., Spacek, M.A., Hetke, J.F. & Swindale, N.V. Polytrodes: high-density silicon electrode arrays for large-scale multiunit recording. J. Neurophysiol. 93, 2987–3000 (2005).

    Article  Google Scholar 

  38. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates (Academic Press, San Diego, 1998).

  39. Sherman, S.M. Dual response modes in lateral geniculate neurons: mechanisms and functions. Vis. Neurosci. 13, 205–213 (1996).

    Article  CAS  Google Scholar 

  40. Bezdudnaya, T. et al. Thalamic burst mode and inattention in the awake LGNd. Neuron 49, 421–432 (2006).

    Article  CAS  Google Scholar 

  41. Barlow, H. Redundancy reduction revisited. Network 12, 241–253 (2001).

    Article  CAS  Google Scholar 

  42. Roberts, M.J. et al. Acetylcholine dynamically controls spatial integration in marmoset primary visual cortex. J. Neurophysiol. 93, 2062–2072 (2005).

    Article  CAS  Google Scholar 

  43. Zilles, K. et al. Distribution of cholinergic receptors in the rat and human neocortex. EXS 57, 212–228 (1989).

    CAS  PubMed  Google Scholar 

  44. Kimura, F., Fukuda, M. & Tsumoto, T. Acetylcholine suppresses the spread of excitation in the visual cortex revealed by optical recording: possible differential effect depending on the source of input. Eur. J. Neurosci. 11, 3597–3609 (1999).

    Article  CAS  Google Scholar 

  45. Metherate, R. & Ashe, J.H. Nucleus basalis stimulation facilitates thalamocortical synaptic transmission in the rat auditory cortex. Synapse 14, 132–143 (1993).

    Article  CAS  Google Scholar 

  46. Parent, A., Pare, D., Smith, Y. & Steriade, M. Basal forebrain cholinergic and noncholinergic projections to the thalamus and brainstem in cats and monkeys. J. Comp. Neurol. 277, 281–301 (1988).

    Article  CAS  Google Scholar 

  47. Lin, S.C., Gervasoni, D. & Nicolelis, M.A. Fast modulation of prefrontal cortex activity by basal forebrain noncholinergic neuronal ensembles. J. Neurophysiol. 96, 3209–3219 (2006).

    Article  Google Scholar 

  48. Zhang, F., Aravanis, A.M., Adamantidis, A., de Lecea, L. & Deisseroth, K. Circuit-breakers: optical technologies for probing neural signals and systems. Nat. Rev. Neurosci. 8, 577–581 (2007).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  50. Hazan, L., Zugaro, M. & Buzsaki, G. Klusters, NeuroScope, NDManager: a free software suite for neurophysiological data processing and visualization. J. Neurosci. Methods 155, 207–216 (2006).

    Article  Google Scholar 

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Acknowledgements

We thank T. Blanche, D. Feldman, R. Froemke, D. Jones, D. Kleinfeld, C. Niell and A. Vahidnia for technical help and useful discussions. This work was supported by grants from the US National Institutes of Health to Y.D. and a Ruth L. Kirschstein National Research Service Award to M.G. (award number F31NS059258 from the US National Institute of Neurological Disorders and Stroke).

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M.G. conducted all of the experiments. M.G. and Y.D. designed the experiments and wrote the manuscript.

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Correspondence to Yang Dan.

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Supplementary Figures 1–7 and Supplementary Table 1 (PDF 988 kb)

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Goard, M., Dan, Y. Basal forebrain activation enhances cortical coding of natural scenes. Nat Neurosci 12, 1444–1449 (2009). https://doi.org/10.1038/nn.2402

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