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Septo-hippocampal GABAergic signaling across multiple modalities in awake mice

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Abstract

Hippocampal interneurons receive GABAergic input from the medial septum. Using two-photon Ca2+ imaging of axonal boutons in hippocampal CA1 of behaving mice, we found that populations of septo-hippocampal GABAergic boutons were activated during locomotion and salient sensory events; sensory responses scaled with stimulus intensity and were abolished by anesthesia. We found similar activity patterns among boutons with common putative postsynaptic targets, with low-dimensional bouton population dynamics being driven primarily by presynaptic spiking.

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Figure 1: Functional imaging of SH-GABA boutons in CA1 of behaving mice.
Figure 2: SH-GABA bouton population dynamics.
Figure 3: Factors contributing to bouton population activity patterns.

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Acknowledgements

We thank C. Lacefield for advice on the behavioral apparatus, L. Paninski for advice on the motion correction algorithm, J. Zaremba, N. Danielson, K. Shakman and A. Castro for programming assistance, M. Morishima for help with immunohistochemistry, and B.V. Zemelman for help with mice and viruses. We thank J.C. Magee, S.A. Siegelbaum, L.F. Abbott and T.M. Jessell for comments on the manuscript. The authors thank the GENIE Program and the Janelia Farm Research Campus of the Howard Hughes Medical Institute for the kind gift of the GCaMP variant 354. This work was funded by the Howard Hughes Medical Institute International Student Research Fellowship Program (P.K.), Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarships (P.K. and M.L.-B.), the Searle Scholars Program, the Human Frontier Science Program, and the Kavli Institute at Columbia University (A.L.).

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Authors and Affiliations

Authors

Contributions

P.K. designed and built hardware and software for imaging, behavior and motion-correction, and performed analyses. M.L.-B., G.F.T. and A.L. performed experiments. T.R.R. performed pseudo-type rabies trans-synaptic labeling. All of the authors wrote the manuscript.

Corresponding authors

Correspondence to Patrick Kaifosh or Attila Losonczy.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–12 (PDF 3373 kb)

Supplementary Video 1

The dynamics of GCaMP signals overlayed upon the static tdTomato background can be viewed. Description: Example of time frame images after motion-correction and channel separation detailed in Supplementary Figure 3. (AVI 24412 kb)

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Kaifosh, P., Lovett-Barron, M., Turi, G. et al. Septo-hippocampal GABAergic signaling across multiple modalities in awake mice. Nat Neurosci 16, 1182–1184 (2013). https://doi.org/10.1038/nn.3482

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