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Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal

Nature Neuroscience volume 7, pages 398–403 (2004)Cite this article

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Abstract

Noxious stimuli have motivational power and can support associative learning, but the neural circuitry mediating such avoidance learning is poorly understood. The anterior cingulate cortex (ACC) is implicated in the affective response to noxious stimuli and the motivational properties of conditioned stimuli that predict noxious stimulation. Using conditioned place aversion (CPA) in rats, we found that excitatory amino acid microinjection into the ACC during conditioning produces avoidance learning in the absence of a peripheral noxious stimulus. Furthermore, microinjection of an excitatory amino acid antagonist into the ACC during conditioning blocked learning elicited by a noxious stimulus. ACC lesions made after conditioning did not impair expression of CPA. Thus, ACC neuronal activity is necessary and sufficient for noxious stimuli to produce an aversive teaching signal. Our results support the idea that a shared ACC pathway mediates both pain-induced negative affect and a nociceptor-driven aversive teaching signal.

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Figure 1: ACC lesions after training do not affect expression of place aversion.
Figure 2: Intra-r-ACC microinjection of the ionotropic glutamate receptor antagonist kynurenic acid (KyA) blocks F-CPA.
Figure 3: CPA is produced by glutamatergic stimulation of the r-ACC.

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  • 14 March 2004

    appended aop PDF with erratum PDF (will be corrected for print issue), updated Figure 2, and placed footnote in SGML at all occurrences of Figure 2

Notes

  1. *Note: In the version of this article initially published online, the y-axis label in Fig. 2a is incorrect. The correct label should be (pre-conditioning -- post-conditioning). This error has been corrected for the HTML and print versions of this article.

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Acknowledgements

The authors thank I. Meng for valuable discussions throughout the course of this work. We also thank G. Hjelmstad, J. Levine, J. Mitchell and S. Nicola for reading this manuscript, and C. Evans and C. Bryant for assistance in the completion of this study. Supported by a United States Public Health Service grant NS 21445.

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  1. Joshua P Johansen

    Present address: Interdepartmental Ph.D. Program for Neuroscience, UCLA, Los Angeles, California, 90095, USA

Authors and Affiliations

  1. Departments of Neurology and Physiology, University of California, San Francisco, 513 Parnassus Avenue, S-784, San Francisco, 94143-0453, California, USA

    Joshua P Johansen & Howard L Fields

  2. The W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, 513 Parnassus Avenue, S-784, San Francisco, 94143-0453, California, USA

    Joshua P Johansen & Howard L Fields

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Correspondence to Howard L Fields.

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Johansen, J., Fields, H. Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal. Nat Neurosci 7, 398–403 (2004). https://doi.org/10.1038/nn1207

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