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Self-modulation of neocortical pyramidal neurons by endocannabinoids

Abstract

Control of pyramidal neuron excitability is vital for the functioning of the neocortex. Somatodendritic slow self-inhibition (SSI) allows inhibitory neurons to regulate their own activity, but the existence of similar mechanisms in excitatory cells has not been shown. We found that in rodents endocannabinoids mediated SSI and long-term modulation of inhibitory connections in layer 2/3 pyramidal neurons with a distinct dendritic morphology, suggesting that a glutamatergic network in cortical circuits is self-regulated.

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Figure 1: Endocannabinoid-mediated slow self-inhibition in neocortical layer 2/3 pyramidal neurons.
Figure 2: SSI is mediated by persistent CB1R activation and is mimicked by CB1R agonists.
Figure 3: SSI identifies a morphological subtype of neocortical pyramidal neurons.

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Acknowledgements

We thank N. Berretta (Fondazione Santa Lucia) for insightful discussion, and P. Mendez-Garcia (European Brain Research Institute) and J. Lourenço (INSERM) for critically reading the manuscript. We are grateful to M. Ammassari-Teule (CNR–Institute of Neuroscience and Fondazione Santa Lucia) for the use of Neurolucida, and to M. Watanabe (Hokkaido University School of Medicine) for the gift of CB1 antibody. This work was supported by the Giovanni Armenise-Harvard Foundation (Career Development Award to A.B.), the European Commission (a Marie Curie International Reintegration Grant to A.B.), the European Research Council (ERC) under the European Community's 7th Framework Programme (FP7/2007-2013, ERC grant agreement number 200808, A.B.), the Italian Institute of Technology (A.B.), Avenir INSERM (in partnership with the Fondation Bettencourt-Schueller, G.M.), Agence National de la Rechereche (G.M.), Region Aquitaine (G.M.), the European Commission Coordination Action ENINET (contract number LSHM-CT-2005-19063 to A.B. and G.M.). A.B. is the 2007/2008 National Alliance for Research on Schizophrenia and Depression Henry and William Test Investigator.

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Authors

Contributions

S.M. and A.B. designed the experiments, S.M. conducted all of the electrophysiological experiments, and S.P. performed the immunhistochemistry and morphological analyses. S.M., S.P. and A.B. analyzed the data. A.C. and G.M. performed the in situ hybridization and provided the mutant mice. S.M., G.M. and A.B. wrote the manuscript.

Corresponding author

Correspondence to Alberto Bacci.

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Supplementary Figures 1–4, Supplementary Tables 1, 2 and Supplementary Methods (PDF 3289 kb)

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Marinelli, S., Pacioni, S., Cannich, A. et al. Self-modulation of neocortical pyramidal neurons by endocannabinoids. Nat Neurosci 12, 1488–1490 (2009). https://doi.org/10.1038/nn.2430

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