Layer-specific excitatory circuits differentially control recurrent network dynamics in the neocortex

Abstract

In the absence of external stimuli, the mammalian neocortex shows intrinsic network oscillations. These dynamics are characterized by translaminar assemblies of neurons whose activity synchronizes rhythmically in space and time. How different cortical layers influence the formation of these spontaneous cellular assemblies is poorly understood. We found that excitatory neurons in supragranular and infragranular layers have distinct roles in the regulation of intrinsic low-frequency oscillations in mice in vivo. Optogenetic activation of infragranular neurons generated network activity that resembled spontaneous events, whereas photoinhibition of these same neurons substantially attenuated slow ongoing dynamics. In contrast, light activation and inhibition of supragranular cells had modest effects on spontaneous slow activity. This study represents, to the best of our knowledge, the first causal demonstration that excitatory circuits located in distinct cortical layers differentially control spontaneous low-frequency dynamics.

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Figure 1: Optogenetic activation of a subpopulation of layer V pyramidal neurons generates network up state–like transitions.
Figure 2: Stimulation of layer II/III principal neurons results in population events that differ from spontaneous up states.
Figure 3: Rhythmic stimulation of a minority of layer V pyramidal neurons entrains ongoing population activity.
Figure 4: Rhythmic stimulation of layer II/III cells does not entrain spontaneous population activity.
Figure 5: Inhibition of a subpopulation of layer V pyramidal neurons attenuates recurrent spontaneous activity.
Figure 6: Inhibition of layer II/III does not affect spontaneous population activity.
Figure 7: Differential spread of excitation after initial activation of subpopulations of layer V and layer II/III pyramids.

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Acknowledgements

We thank J. Assad, A. Bacci, F. Benfenati, A. Blau and G. Carmignoto for critical reading and helpful comments on the manuscript. We thank C. Gerfen (US National Institute of Mental Health) for Rbp4-cre mice, K. Deisseroth (Stanford University) for pAAV-EF1a.DIO.hChR2(H134R)-EYFP.WPRE.hGH (Addgene 20298), pAAV-EF1.dflox.hChR2(H134R)-mCherry.WPRE.hGH (Addgene 20297) and pAAV-EF1a.DIO.eNpHR-eYFP.WP.hGH (Addgene 20949), K. Svoboda (Howard Hughes Medical Institute, Janelia Farm) for pCAGGS-ChR2-Venus (Addgene 15753), E. Boyden (Massachusetts Institute of Technology) for pAAV-CAG-ArchT-GFP (Addgene 29777), FCK-Arch-GFP (Addgene 22217) and AAV2/1.flex.CBA.Arch-GFP.WPRE.SV40 (Addgene 22222) and S. Guazzi for subcloning and amplification of some of the plasmids used in this study. This work was supported by the Italian Institute of Technology and grants from San Paolo “Programma in Neuroscienze”, MIUR FIRB (RBAP11X42L) and Telethon-Italy (GGP10138) to T.F.

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R.B., G.D., M.D.M., P.F. and T.F. performed all experiments and analysis presented in this manuscript. S.B. and T.F. performed viral injections. Y.C. performed initial in utero electroporation experiments. R.B., Y.C., D.D.P.T. and T.F. designed in utero electroporation experiments. G.L. and V.T. provided assistance with EEG recordings on behaving animals. D.D.P.T. provided reagents. T.F. conceived and coordinated the project. T.F. wrote the paper. All authors approved the final version of the manuscript.

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Correspondence to Tommaso Fellin.

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Beltramo, R., D'Urso, G., Dal Maschio, M. et al. Layer-specific excitatory circuits differentially control recurrent network dynamics in the neocortex. Nat Neurosci 16, 227–234 (2013). https://doi.org/10.1038/nn.3306

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