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A neuronal analogue of state-dependent learning

Nature volume 403, pages 549–553 (2000)Cite this article

Abstract

State-dependent learning is a phenomenon in which the retrieval of newly acquired information is possible only if the subject is in the same sensory context and physiological state as during the encoding phase1. In spite of extensive behavioural and pharmacological characterization2, no cellular counterpart of this phenomenon has been reported. Here we describe a neuronal analogue of state-dependent learning in which cortical neurons show an acetylcholine-dependent expression of an acetylcholine-induced functional plasticity. This was demonstrated on neurons of rat somatosensory ‘barrel’ cortex, whose tunings to the temporal frequency of whisker deflections were modified by cellular conditioning. Pairing whisker stimulation with acetylcholine applied iontophoretically yielded selective lasting modification of responses, the expression of which depended on the presence of exogenous acetylcholine. Administration of acetylcholine during testing revealed frequency-specific changes in response that were not expressed when tested without acetylcholine or when the muscarinic antagonist, atropine, was applied concomitantly. Our results suggest that both acquisition and recall can be controlled by the cortical release of acetylcholine.

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Figure 1: Plasticity of cortical responses expressed during ACh application in four different units.
Figure 2: Statistical analysis of ACh-induced response modifications for all tested units.
Figure 3: Reorganization of TFTCs expressed with ACh after pairing.
Figure 4: Atropine blocks the ACh-dependent expression of plasticity.

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References

  1. Izquierdo, I. in Neurobiology of Learning and Memory (eds Lynch, G., McGaugh, J. L. & Weinberger, N. M.) 333–358 (Guilford, New York, 1984).

    Google Scholar 

  2. Gordon, W. C. & Klein, R. L. in Animal Learning and Cognition (ed. Mackintosh, N. J.) 255–279 (Academic, San Diego, 1994).

    Book  Google Scholar 

  3. Mesulam, M. M., Mufson, E. J., Wainer, B. H. & Levey, A. I. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1–Ch6). Neuroscience 10, 1185–1201 (1983).

    Article  CAS  Google Scholar 

  4. Richardson, R. T. & DeLong, M. R. A reappraisal of the functions of the nucleus basalis of Meynert. Trends Neurosci. 11, 264–267 ( 1988).

    Article  CAS  Google Scholar 

  5. Singer, W. in Brain Organization and Memory: Cells, Systems, and Circuits (eds McGaugh, J. L., Weinberger, N. M. & Lynch, G.) 211–233 (Oxford Univ. Press, New York, 1990).

    Google Scholar 

  6. Ahissar, E. & Ahissar, M. Plasticity in auditory cortical circuitry. Curr. Opin. Neurobiol. 4, 580– 587 (1994).

    Article  CAS  Google Scholar 

  7. Weinberger, N. M. Dynamic regulation of receptive fields and maps in the adult sensory cortex. Annu. Rev. Neurosci. 18, 129– 158 (1995).

    Article  CAS  Google Scholar 

  8. Dykes, R. Mechanisms controlling neuronal plasticity in somatosensory cortex. Can. J. Physiol. Pharmacol. 75, 535–545 (1997).

    Article  CAS  Google Scholar 

  9. Edeline, J. M. Learning-induced physiological plasticity in the thalamo-cortical sensory systems: a critical evaluation of receptive field plasticity, map changes and their potential mechanisms. Prog. Neurobiol. 57 , 165–224 (1999).

    Article  CAS  Google Scholar 

  10. Metherate, R. & Weinberger, N. M. Acetylcholine produces stimulus-specific receptive field alterations in cat auditory cortex. Brain Res. 480, 372–377 ( 1989).

    Article  CAS  Google Scholar 

  11. Edeline, J. -M., Hars, B., Maho, C. & Hennevin, E. Transient and prolonged facilitation of tone-evoked responses induced by basal forebrain stimulations in the rat auditory cortex. Exp. Brain Res. 97, 373–386 (1994).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  13. Kilgard, M. P. & Merzenich, M. M. Plasticity of temporal information processing in the primary auditory cortex. Nature Neurosci. 8, 727–731 (1998).

    Article  Google Scholar 

  14. Rasmusson, D. D. & Dykes, R. W. Long-term enhancement of evoked potentials in cat somatosensory cortex produced by co-activation of the basal forebrain and cutaneous receptors. Exp. Brain Res. 70, 276–286 ( 1988).

    Article  CAS  Google Scholar 

  15. Jacobs, S. E. & Juliano, S. L. The impact of basal forebrain lesions on the ability of rats to perform a sensory discrimination task involving barrel cortex. J. Neurosci. 15, 1099– 1109 (1995).

    Article  CAS  Google Scholar 

  16. Baskerville, K. A., Schweitzer, J. B. & Herron, P. Effects of cholinergic depletion on experience-dependent plasticity in the cortex of the rat. Neurosci. 80, 1159–1169 (1997).

    Article  CAS  Google Scholar 

  17. Maalouf, M., Miasnikov, A. A. & Dykes, R. W. Blockade of cholinergic receptors in rat barrel cortex prevents long-term changes in the evoked potential during sensory preconditioning. J. Neurophysiol. 80, 529– 545 (1998).

    Article  CAS  Google Scholar 

  18. Sachdev, R. N., Lu, S. M., Wiley, R. G. & Ebner, F. F. Role of the basal forebrain cholinergic projection in somatosensory cortical plasticity. J. Neurophysiol. 79, 3216–3228 (1998).

    Article  CAS  Google Scholar 

  19. Woolsey, T. A. & Van der Loos, H. 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 (1970).

    Article  CAS  Google Scholar 

  20. Carvel, G. E. & Simons, D. J. Biometric analyses of vibrissal tactile discrimination in the rat. J. Neurosci. 10, 2638–2648 (1990).

    Article  Google Scholar 

  21. Ahissar, E., Haidarliu, S. & Zacksenhouse, M. Decoding temporally encoded sensory input by cortical oscillations and thalamic phase comparators. Proc. Natl Acad. Sci. USA 94, 11633–11638 ( 1997).

    Article  ADS  CAS  Google Scholar 

  22. Webster, H. H. et al. Long-term enhancement of evoked potentials in racoon somatosensory cortex following co-activation of the nucleus basalis of Meynert complex and cutaneous receptors. Brain Res. 545, 292 –296 (1991).

    Article  CAS  Google Scholar 

  23. Howard, M. A. & Simons, D. J. Physiologic effects of nucleus basalis magnocellularis stimulation on rat barrel cortex neurons. Exp. Brain Res. 102, 21–33 (1994).

    Article  Google Scholar 

  24. Ahissar, E., Haidarliu, S. & Shulz, D. E. Possible involvement of neuromodulatory systems in cortical Hebbian-like plasticity. J. Physiol. (Paris) 90, 353–360 (1996).

    Article  CAS  Google Scholar 

  25. Delacour, J., Houcine, O. & Costa, J. C. Evidence for a cholinergic mechanism of “learned” changes in the responses of barrel field neurons of the awake and undrugged rat. Neuroscience 34, 1– 8 (1990).

    Article  CAS  Google Scholar 

  26. Shulz, D. E., Cohen, S., Haidarliu, S. & Ahissar, E. Differential effects of acetylcholine on neuronal activity and interactions in the auditory cortex of the guinea-pig. Eur. J. Neurosci. 9, 396–409 (1997).

    Article  CAS  Google Scholar 

  27. Haidarliu, S. & Ahissar, E. Spatial organization of facial vibrissae and cortical barrels in the guinea pig and golden hamster. J. Comp. Neurol. 385, 515–527 ( 1997).

    Article  CAS  Google Scholar 

  28. Haidarliu, S. An anatomically adapted, injury-free headholder for guinea pigs. Physiol. Behav. 60, 111–114 (1996).

    Article  CAS  Google Scholar 

  29. Haidarliu, S., Shulz, D. E. & Ahissar, E. A multi-electrode array for combined microiontophoresis and multiple single-unit recordings. J. Neurosci. Meth. 56, 125–131 (1995).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Y. Dudai, Y. Frégnac, H. Markram, P. Salin and M. Segal for helpful comments, and A. Bagady for help with statistical analysis. V.E. and D.E.S. were supported by the French Embassy in Israel during their visits to the laboratory of E.A. where the experiments were done. This work was supported by PICS CNRS, Ministère des Affaires Etrangères Français, AFIRST, HFSP, US-Israel Binational Science Foundation, Israel and the MINERVA Foundation, Germany.

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Authors and Affiliations

  1. Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel

    R. Sosnik, S. Haidarliu & E. Ahissar

  2. Equipe Cognisciences, UNIC, Institut A. Fessard, CNRS, 91198 Gif sur Yvette, France

    D. E. Shulz & V. Ego

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  1. D. E. Shulz
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  4. S. Haidarliu
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Correspondence to D. E. Shulz.

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Shulz, D., Sosnik, R., Ego, V. et al. A neuronal analogue of state-dependent learning. Nature 403, 549–553 (2000). https://doi.org/10.1038/35000586

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