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Protein kinase C acts as a molecular detector of firing patterns to mediate sensory gating in Aplysia

Nature Neuroscience volume 15, pages 1144–1152 (2012)Cite this article

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Abstract

Habituation of a behavioral response to a repetitive stimulus enables animals to ignore irrelevant stimuli and focus on behaviorally important events. In Aplysia, habituation is mediated by rapid depression of sensory synapses, which could leave an animal unresponsive to important repetitive stimuli, making it vulnerable to injury. We identified a form of plasticity that prevents synaptic depression depending on the precise stimulus strength. Burst-dependent protection from depression is initiated by trains of 2–4 action potentials and is distinct from previously described forms of synaptic enhancement. The blockade of depression is mediated by presynaptic Ca2+ influx and protein kinase C (PKC) and requires localization of PKC via a PDZ domain interaction with Aplysia PICK1. During protection from depression, PKC acts as a highly sensitive detector of the precise pattern of sensory neuron firing. Behaviorally, burst-dependent protection reduces habituation, enabling animals to maintain responsiveness to stimuli that are functionally important.

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Figure 1: Bursts of two to four spikes in presynaptic sensory neurons protect against development of HSD and partially reverse previously developed HSD.
Figure 2: Effect of BDP on sensory neuron synapses is stable, distinguishing BDP from PTP.
Figure 3: Initiation of BDP involves presynaptic Ca2+ influx.
Figure 4: Initiation of BDP involves PKC, but not CaMKII.
Figure 5: The Ca2+-activated PKC Apl-I interacts with the PDZ domain protein Aplysia PICK1.
Figure 6: BDP depends on PDZ domain interactions.
Figure 7: Bursts of spikes in siphon sensory neurons reduce habituation of siphon withdrawal response via a homosynaptic mechanism.

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Acknowledgements

We thank W. Sossin, S. Thompson and E. Walters for commenting on an earlier version of this manuscript. We thank P. Shrestha for performing the co-immunoprecipitation and immunoblot experiments. We thank I. Antonov and R. Hawkins for introducing us to their behavioral preparation. This work was supported by US National Institutes of Health grant R01 MH-55880 to T.W.A.

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  1. Qin Wan and Xue-Ying Jiang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Qin Wan, Xue-Ying Jiang, Andreea M Negroiu, Shao-Gang Lu & Thomas W Abrams

  2. Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Kimberly S McKay & Thomas W Abrams

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Contributions

X.-Y.J. and T.W.A. discovered the BDP phenomenon. Q.W., K.S.M. and T.W.A. designed the experiments. Q.W., X.-Y.J., A.M.N. and S.-G.L. carried out the experiments analyzing the mechanism of BDP. K.S.M. performed the behavioral experiments. T.W.A., K.S.M. and Q.W. wrote the paper.

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Correspondence to Thomas W Abrams.

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Wan, Q., Jiang, XY., Negroiu, A. et al. Protein kinase C acts as a molecular detector of firing patterns to mediate sensory gating in Aplysia. Nat Neurosci 15, 1144–1152 (2012). https://doi.org/10.1038/nn.3158

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