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OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons

Abstract

The vast diversity of GABAergic interneurons is believed to endow hippocampal microcircuits with the required flexibility for memory encoding and retrieval. However, dissection of the functional roles of defined interneuron types has been hampered by the lack of cell-specific tools. We identified a precise molecular marker for a population of hippocampal GABAergic interneurons known as oriens lacunosum-moleculare (OLM) cells. By combining transgenic mice and optogenetic tools, we found that OLM cells are important for gating the information flow in CA1, facilitating the transmission of intrahippocampal information (from CA3) while reducing the influence of extrahippocampal inputs (from the entorhinal cortex). Furthermore, we found that OLM cells were interconnected by gap junctions, received direct cholinergic inputs from subcortical afferents and accounted for the effect of nicotine on synaptic plasticity of the Schaffer collateral pathway. Our results suggest that acetylcholine acting through OLM cells can control the mnemonic processes executed by the hippocampus.

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Figure 1: Chrna2 is a marker for CA1 OLM interneurons.
Figure 2: OLMα2 cells inhibit interneurons that synapse on pyramidal cell proximal dendrites.
Figure 3: OLMα2 cells suppress LTP in the temporoammonic pathway.
Figure 4: OLMα2 cells enhance LTP in the Schaffer collateral pathway.
Figure 5: OLMα2 cells receive remote cholinergic input.

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Acknowledgements

We thank G. Buzsaki, P. Ascher, B. Lamotte d'Incamps, O. Amaral and E. Hanse for comments on earlier versions of this manuscript. This work was supported by the foundations of Märta och Kjell Beijer, Hållsten and Göran Gustafsson, The Swedish Foundation for International Cooperation in Research and Higher Education, the Brazilian Federal Agency for Support and Evaluation of Graduate Education, the Brazilian National Council of Technological and Scientific Development, the Research Support Agency of the State of Rio Grande do Norte, US National Institutes of Health grant R01EB001963, the Swedish Medical Research Council, the Swedish Brain Foundation, and Uppsala University. K.K. is a Royal Swedish Academy of Sciences Research Fellow supported by a grant from the Knut and Alice Wallenberg Foundation.

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H.G., A. Enjin and K.K. designed and produced the transgenic mice. R.N.L., K.E.L., A.B.L.T., L.M.L. and K.K. designed the experiments. R.N.L., K.E.L., S.M., H.M., K.P. and A. Eriksson performed the experiments. R.N.L., K.E.L., A.B.L.T. and K.K. analyzed data and wrote the paper.

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Correspondence to Richardson N Leão or Klas Kullander.

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Leão, R., Mikulovic, S., Leão, K. et al. OLM interneurons differentially modulate CA3 and entorhinal inputs to hippocampal CA1 neurons. Nat Neurosci 15, 1524–1530 (2012). https://doi.org/10.1038/nn.3235

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