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Parvalbumin-positive CA1 interneurons are required for spatial working but not for reference memory

Abstract

Parvalbumin-positive GABAergic interneurons in cortical circuits are hypothesized to control cognitive function. To test this idea directly, we functionally removed parvalbumin-positive interneurons selectively from hippocampal CA1 in mice. We found that parvalbumin-positive interneurons are dispensable for spatial reference, but are essential for spatial working memory.

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Figure 1: Selective expression of TeLC in parvalbumin-positive interneurons of the hippocampus.
Figure 2: Blocking parvalbumin-positive cell–mediated inhibition in the hippocampus impairs spatial working but not reference memory.

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Acknowledgements

We thank M. Klugmann and T. Kuner for AAV plasmids and technical advice, E. Fuchs and H. Monyer for Pvalb-cre mice, R. Yu for tetanus toxin light chain cDNA, D. Kuhl for the Arc/Arg3.1 cDNA, T. Goetz for bringing the FLEX system to our attention, C. Black for participation in the initial cloning of AAV vectors, P. Teismann and the microscopy core facility at the University of Aberdeen for the use of microscopy equipment, and L. Strachan, A. Plano and S. Deiana for help with surgeries and behavioral testing. We were supported by the Northern Research Partnership (J.-F.S.), Biotechnology and Biological Sciences Research Council grant BB/H001123/1 (P.W.), the Royal Society (M.B. and P.W.), the University of Aberdeen (M.B., W.W. and P.W.), the J. Ernest Tait Estate (W.W.), the Lichtenberg Award (M.B.) and Medical Research Council grants G0800401 (G.R.) and G0601498 (W.W. and P.W.).

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A.J.M., J.-F.S., G.R., L.A., M.B., W.W. and P.W. designed the experiments. A.J.M., J.-F.S., C.M., L.A. and L.C. performed the experiments. Anatomical data were analyzed by A.J.M., L.A. and P.W. Electrophysiological data were analyzed by J.-F.S. and M.B. Behavioral data were analyzed by A.J.M., P.W. and G.R. A.J.M., G.R., J.-F.S., M.B., W.W. and P.W. co-wrote the manuscript.

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Correspondence to William Wisden or Peer Wulff.

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The authors declare no competing financial interests.

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Supplementary Figures 1–8 and Supplementary Methods (PDF 2372 kb)

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Murray, A., Sauer, JF., Riedel, G. et al. Parvalbumin-positive CA1 interneurons are required for spatial working but not for reference memory. Nat Neurosci 14, 297–299 (2011). https://doi.org/10.1038/nn.2751

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