Abstract
Visual experience during a critical period early in postnatal development can change connections within mammalian visual cortex. In a kitten at the peak of the critical period (∼P28–42), brief monocular deprivation can lead to complete dominance by the open eye, an ocular dominance shift. This process is driven by activity from the eyes, and depends on N-methyl-D-aspartate (NMDA) receptor activation. The components of the intracellular signaling cascade underlying these changes have not all been identified. Here we show that inhibition of protein kinase A (PKA) by Rp-8-Cl-cAMPS blocks ocular dominance shifts that occur following monocular deprivation early in the critical period. Inhibition of protein kinase G by Rp-8-Br-PET-cGMPS had no effect, indicating a specificity for the PKA pathway. Enhancement of PKA activity late in the critical period with Sp-8-Cl-cAMPS did not increase plasticity. PKA is a necessary component of the pathway leading to cortical plasticity during the critical period.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Dubnau, J. & Tully, T. Gene discovery in Drosophila: new insights for learning and memory. Annu. Rev. Neurosci. 21, 407–444 (1998).
Abel, T. & Kandel, E. R. Positive and negative regulatory mechanisms that mediate long-term memory storage. Brain Res. Rev. 26, 360–378 (1998).
Brandon E. P., Idzerda R. L. & McKnight, G. S. PKA isoforms, neural pathways, and behaviour: making the connection. Curr. Opin. Neurobiol. 7, 397–403 (1997).
Weisskopf, M. G., Castillo, P. E., Zalutsky, R. A. & Nicoll, R. A. Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP. Science 265, 1878–1882 (1994).
Wong, S. T. et al. Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP. Neuron 23, 787–798 (1999).
Tzounopoulos, T., Janz, R., Südhof, T. C., Nicoll, R. A. & Malenka, R. C. A role for cAMP in long-term depression at hippocampal mossy fiber synapses. Neuron 21, 837–845 (1998).
Dixon, D. & Atwood, H. L. Adenylate cyclase system is essential for long-term facilitation at the crayfish neuromuscular junction. J. Neurosci. 9, 4246–4252 (1989).
Trudeau, L.-E., Emery, D. G. & Haydon, P. G. Direct modulation of the secretory machinery underlies PKA-dependent synaptic facilitation in hippocampal neurons. Neuron 17, 789–797 (1996).
Chavez-Noriega, L. E. & Stevens, C. F. Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices. J. Neurosci. 14, 310–317 (1994).
Greengard, P., Jen, J., Nairn, A. C. & Stevens, C. F. Enhancement of the glutamate response by cAMP-dependent protein kinase in hippocampal neurons. Science 253, 1135–1138 (1991).
Wang, L.-Y., Salter, M. W. & MacDonald, J. F. Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases. Science 253, 1132–1134 (1991).
Montminy, M. Transcriptional regulation by cyclic AMP. Annu. Rev. Biochem. 66, 807–822 (1997).
Wiesel, T. N. & Hubel, D. H. Single cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol. 26, 1003–1017 (1963).
Shatz, C. J. & Stryker, M. P. Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation. J. Physiol. (Lond.) 281, 267–283 (1978).
Bear, M. F., Kleinschmidt, A., Gu, Q. & Singer, W. Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist. J. Neurosci. 10, 909–925 (1990).
Daw, N. W. et al. Injection of MK-801 affects ocular dominance shifts more than visual activity. J. Neurophysiol. 81, 204–215 (1999).
Reid, S. N., Daw, N. W., Gregory, D. S. & Flavin, H. cAMP levels increased by activation of metabotropic glutamate receptors correlate with visual plasticity. J. Neurosci. 16, 7619–7626 (1996).
Mower, G. D. The effect of dark rearing on the time course of the critical period in cat visual cortex. Dev. Brain Res. 58, 151–158 (1991).
Hensch T. K. et al. Comparison of plasticity in vivo and in vitro in the developing visual cortex of normal and protein kinase A RIβ-deficient mice. J. Neurosci. 18, 2108–2117 (1998).
Amieux, P. S. et al. Compensatory regulation of RIα protein levels in protein kinase A mutant mice. J. Biol. Chem. 272, 3993–3998 (1997).
Dostmann, R. G. et al. Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3′,5′-cyclic phosphorothioates. J. Biol. Chem. 265, 10484–10491 (1990).
Bois, P., Renaudon, B., Baruscotti, M., Lenfant, J. & DiFrancesco, D. Activation of f-channels by cAMP analogues in macropatches from rabbit sino-atrial node myocytes. J. Physiol. (Lond.) 501, 565–571 (1997).
Kramer, R. H. & Tibbs, G. R. Antagonists of cyclic nucleotide-gated channels and molecular mapping of their site of action. J. Neurosci. 16, 1285–1293 (1996).
Zhuo, M., Hu, Y., Schultz, C., Kandel, E. R. & Hawkins, R. D. Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation. Science 269, 635–639 (1994).
Gage, A. T., Reyes, M. & Stanton, P. K. Nitric-oxide-guanylyl-cyclase-dependent and -independent components of multiple forms of long-term synaptic depression. Hippocampus 7, 286–295 (1997).
Butt, E., Pöhler, D., Genieser, H.-G., Huggins, J. P. & Bucher, B. Inhibition of cyclic GMP-dependent protein kinase-mediated effects by (Rp)-8-bromo-PET-cyclic GMPS. Br. J. Pharmacol. 116, 3110–3116 (1995).
Wei, J.-Y., Cohen, E. D., Yan, Y.-Y., Geniesser, H.-G. & Barnstable, C. J. Identification of competitive antagonists of the rod photoreceptor cGMP-gated cation channel: β-phenyl-1, N2 –etheno-substituted cGMP analogues of probes of the cGMP binding site. Biochemistry 35, 16815–16823 (1996).
Olson, C. R. & Freeman, R. D. Profile of the sensitive period for monocular deprivation in kittens. Exp. Brain Res. 39, 17–21 (1980).
Reid, S. N., Daw, N. W., Czepita, D., Flavin, H. J. & Sessa, W. C. Inhibition of nitric oxide synthase does not alter ocular dominance shifts in kitten visual cortex. J. Physiol. (Lond.) 494, 511–517 (1996).
Ruthazer, E. S., Gillespie, D. C., Dawson, T. M., Snyder, S. H. & Stryker, M. P. Inhibition of nitric oxide synthase does not prevent ocular dominance plasticity in kitten visual cortex. J. Physiol. (Lond.) 494, 519–527 (1996).
Gordon, B., Daw, N. W. & Parkinson, D. The effect of age on binding of MK-801 in the cat visual cortex. Brain Res. Dev. Brain Res. 62, 61–67 (1991).
Chetkovich, D. M., Gray, R., Johnston, D. & Sweatt, J. D. N-methyl-d-aspartate receptor activation increases cAMP levels and voltage gated Ca2+ channel activity in area CA1 of hippocampus. Proc. Natl. Acad. Sci. USA 88, 6467–6471 (1991).
Roberson, E. D. & Sweatt, J. D. Transient activation of cyclic AMP-dependent protein kinase during hippocampal long-term potentiation. J. Biol. Chem. 271, 30436–30441 (1996).
Bear, M. F. & Singer, W. Modulation of visual cortical plasticity by acetylcholine and noradrenaline. Nature 320, 172–176 (1986).
Cerne, R., Rusin, K. I. & Randic, M. Enhancement of the N-methyl-d-aspartate response in spinal dorsal horn neurons by cAMP-dependent protein kinase. Neurosci. Lett. 161, 124–128 (1993).
Blackstone, C., Murphy, T. H., Moss, S. J., Baraban, J. M. & Huganir, R. L. Cyclic AMP and synaptic activity dependent phosphorylation of AMPA-preferring glutamate receptors. J. Neurosci. 14, 7585–7593 (1994).
Kano, M. & Konnerth, A. Potentiation of GABA-mediated currents by cAMP-dependent protein kinase. Neuroreport 3, 563–566 (1992).
Poisbeau, P., Cheney, M. C., Browning, M. D. & Mody, I. Modulation of synaptic GABAA receptor function by PKA and PKC in adult hippocampal neurons. J. Neurosci. 19, 674–683 (1999).
Pham, T. A., Impey, S., Storm, D. R. & Stryker, M. P. CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period. Neuron 22, 63–72 (1999).
Mower, G. D. & Kaplan, I. V. Fos expression during the critical period in visual cortex: differences between normal and dark reared cats. Brain Res. Dev. Brain Res. 64, 264–269 (1999).
Imamura, K., Kasamatsu, T., Shirokawa, T. & Ohashi, T. Restoration of ocular dominance plasticity mediated by adenosine 3′,5′-monophosphate in adult visual cortex. Proc. R. Soc. (Lond.) B Biol. Sci. 266, 1507–1516 (1999).
Bach, M. E. et al. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc. Natl. Acad. Sci. USA 96, 5280–5285 (1999).
Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. (Lond.) 160, 106–154 (1962).
Acknowledgements
This work was supported by Public Service Grant # RO1 EY00053. Core facilities in the department are supported by Research to Prevent Blindness. The authors thank A. Roe and D. Mitchell for comments on the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Beaver, C., Ji, Q., Fischer, Q. et al. Cyclic AMP-dependent protein kinase mediates ocular dominance shifts in cat visual cortex. Nat Neurosci 4, 159–163 (2001). https://doi.org/10.1038/83985
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/83985
This article is cited by
-
Laminar analysis of the role of GluR1 in experience-dependent and synaptic depression in barrel cortex
Nature Neuroscience (2008)
-
Cytoskeleton as a potential target in the neuropathology of maple syrup urine disease: Insight from animal studies
Journal of Inherited Metabolic Disease (2007)
-
Protein kinase A regulates calcium permeability of NMDA receptors
Nature Neuroscience (2006)
-
Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex
Nature Neuroscience (2005)
-
Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development
Nature Neuroscience (2003)