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PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation

Nature Neuroscience volume 19, pages 454–464 (2016)Cite this article

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An Author Correction to this article was published on 16 July 2018

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Abstract

Long-term consolidation of memories depends on processes occurring many hours after acquisition. Whether this involves plasticity that is specifically required for long-term consolidation remains unclear. We found that learning-induced plasticity of local parvalbumin (PV) basket cells was specifically required for long-term, but not short/intermediate-term, memory consolidation in mice. PV plasticity, which involves changes in PV and GAD67 expression and connectivity onto PV neurons, was regulated by cAMP signaling in PV neurons. Following induction, PV plasticity depended on local D1/5 dopamine receptor signaling at 0–5 h to regulate its magnitude, and at 12–14 h for its continuance, ensuring memory consolidation. D1/5 dopamine receptor activation selectively induced DARPP-32 and ERK phosphorylation in PV neurons. At 12–14 h, PV plasticity was required for enhanced sharp-wave ripple densities and c-Fos expression in pyramidal neurons. Our results reveal general network mechanisms of long-term memory consolidation that requires plasticity of PV basket cells induced after acquisition and sustained subsequently through D1/5 receptor signaling.

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Figure 1: Sustained high-PV plasticity required for long-term memory in definite learning.
Figure 2: Sustained low-PV plasticity required for long-term memory consolidation in incremental learning.
Figure 3: PV neuron plasticity sustained through D1/5 dopamine receptor signaling and regulated by cAMP in PV neurons.
Figure 4: Critical late time window of long-term memory consolidation depending on D1/5 receptor signaling.
Figure 5: D1/5 receptor signaling supports long-term memory consolidation through PV plasticity.
Figure 6: D1/5 signaling at +0–5 h modulates PV plasticity strength and memory.
Figure 7: Enhanced ripple density at +12–14 h depending on PV plasticity.
Figure 8: c-Fos expression peak at +12h−14 h depending on PV plasticity.

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Change history

  • 01 February 2016

    In the version of this article initially published online, Charles Quairiaux and Christoph M Michel were listed as being affiliated with the Friedrich Miescher Institut, Basel, Switzerland. The correct affiliation is Neuroscience Department of the Medical Faculty and Center for Biomedical Imaging, University of Geneva, Geneva, Switzerland. The error has been corrected for the print, PDF and HTML versions of this article.

  • 16 July 2018

    In the version of this article initially published, the right panel in Fig. 2b was duplicated from the corresponding panel in Fig. 2c, and some data points in Fig. 3b were duplicated from Fig. 3a. None of the conclusions in the paper are affected. The errors have been corrected in the HTML and PDF versions of the article, and source data have been posted for the revised panels. The original and corrected figures are shown in the accompanying Author Correction.

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Acknowledgements

F. Carvalho (Friedrich Miescher Institut) found that PV plasticity was influenced by cAMP levels in PV neurons, and we acknowledge his contribution to this study. We thank S. Arber (FMI) for valuable comments on the manuscript. This work was supported in part by a Swiss National Fund grant to P.C. and by the NCCR Synapsy. The Friedrich Miescher Institut is part of the Novartis Research Foundation.

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Author notes

  1. Smitha Karunakaran and Ananya Chowdhury: These authors contributed equally to this work.

Authors and Affiliations

  1. Friedrich Miescher Institut, Basel, Switzerland

    Smitha Karunakaran, Ananya Chowdhury, Flavio Donato & Pico Caroni

  2. Neuroscience Department of the Medical Faculty and Center for Biomedical Imaging, University of Geneva, Geneva, Switzerland

    Charles Quairiaux & Christoph M Michel

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Contributions

S.K. devised and carried out the local DA and PV interference and behavior experiments. A.C. carried out detailed time course analyses of hippocampal PV network plasticity following fear conditioning and maze learning, as well as experiments addressing signaling in PV neurons. F.D. carried out the initial pharmacogenetic and ChABC interference, as well as PV analysis experiments. C.Q. and C.M.M. carried out the LFP experiments. P.C. helped to devise the experiments and wrote the manuscript. All of the authors discussed the results and commented the manuscript.

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Correspondence to Pico Caroni.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 D1/5 receptor signaling at acquisition required for PV plasticity and long-term fear memory consolidation.

a. Analysis of vH D1/5 signaling interference during fear memory acquisition. Note low-PV instead of high-PV shift induction (left), unaffected intermediate-term memory (+6.5h) and absence of long-term fear memory (+24h). b. No rescue of PV plasticity or fear memory by D1 agonist delivery at +12h in mice treated with D1/5 antagonist just before acquisition. Note sustainment of low-PV plasticity by D1 agonist at +12h (left), and absence of fear memory (right). Average values from 4-6 mice and 60 PV neurons each; ANOVA, followed by Dunnet’s post-hoc; p <0.001 (***).

Supplementary Figure 2 Specific suppression of long-term memory consolidation by D1/5 receptor antagonist at +12h.

a. Analysis of average center of mass movement (translocation) velocity in mice subjected to cFC, treated with D1/5 receptor antagonist at different times after acquisition (x-axis), and analyzed at +24h in training context. Note how mice with suppressed fear memory (e.g. +13h) do not move faster than untreated control mice (0h), arguing against loss of freezing due to hyper-locomotion. b. Mice that underwent cFC and were treated with D1/5 antagonist at +12h exhibit robust fear memory at +2d when reconditioned at +24h (orange), indicating that D1/5 antagonist at +12h specifically suppressed long-term consolidation of the fear memory induced 12h before (red). c. NE receptor antagonist delivered at +12h to vH does not interfere with long-term consolidation of fear memory. Average values from 4-6 mice.

Supplementary Figure 3 Specific suppression of individual long-term memories by D1/5 receptor antagonist at +12h.

a. Delivery of D1/5 receptor antagonist to vH at +12h suppresses fear memory consolidation regardless of whether acquisition occurred at 09:00, 15:00 or 21:00. b, c. Memory specific requirement for vH D1/5 receptor signaling at +12h for long-term memory consolidation. b: Specific suppression of TR1 or TR2 fear memory by D1/5 receptor antagonist at +12h after corresponding fear conditioning. c: Enhanced high-PV plasticity upon second cFC protocol, and reversal to high-PV levels comparable to those induced by one cFC protocol upon delivery of D1/5 receptor antagonist at +12h. Average values from 4-6 mice and 60 PV neurons each; Student’s t-test; p<0.001 (***).

Supplementary Figure 4 Pharmacogenetic induction of high-PV plasticity in naïve mice not sufficient to induce freezing.

Mice expressing pharmacogenetic activator virus in vH CA3 PV neurons explored context without foot shocks (noUS), where treated with pharmacogenetic ligand at +3h, and tested for freezing in context at +12h or +24. Average values from 4-6 mice and 60 PV neurons each.

Supplementary Figure 5 No detectable expression of cFos in vH CA3b PV neurons 90min after cFC.

Representative example of c-Fos/PV double-labeling experiment in vH CA3b 90min after cFC. Yellow arrows: PV+ neurons. Bar: 50 μm. Average values from 3 mice and 80 PV neurons each.

Supplementary Figure 6 Analysis of dye spread and electrode paths.

a. Left: Mouse brain coronal section with location of vH (DG, CA3, CA1). Numbers: antero-posterior coordinates caudal to bregma. Right: Representative image of Bodipy dye targeted at vH CA3 and its spread from the target site 6h after injection. Bar, 300μm. b. 16 channel Neuronexus probes (LFP experiments) inserted in both vH with 16 contacts covering 0.8mm length at the electrode tip. Example of electrode track position revealed with Dye I (right). Bar, 1500μm. c. Representative images of Nissl stained vH section (50 μm) through the cannula track after dye injection (left). Bar: 200 μm. Infusion site (dotted line) and injector track (black line) (right). Bar 100 μm. d. Injection sites from 8 mice into CA3 region of vH.

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Karunakaran, S., Chowdhury, A., Donato, F. et al. PV plasticity sustained through D1/5 dopamine signaling required for long-term memory consolidation. Nat Neurosci 19, 454–464 (2016). https://doi.org/10.1038/nn.4231

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