Functional emergence of a column-like architecture in layer 5 of mouse somatosensory cortex in vivo
To investigate how the functional architecture is organized in layer 5 (L5) of the somatosensory cortex of a mouse in vivo, the input–output relationship was investigated using an all-optical approach. The neural activity in L5 was optically recorded using a Ca2+ sensor, R-CaMP2, through a microprism inserted in the cortex under two-photon microscopy, while the L5 was regionally excited using optogenetics. The excitability was spread around the blue-light irradiated region, but the horizontal propagation was limited to within a certain distance (λ < 130 μm from the center of the illumination spot). When two regions were photostimulated with a short interval, the excitability of each cluster was reduced. Therefore, a column-like architecture had functionally emerged with reciprocal inhibition through a minimal number of synaptic relays. This could generate a synchronous output from a region of L5 with simultaneous enhancement of the signal-to-noise ratio by silencing of the neighboring regions.
KeywordsOptogenetics Ca2+ imaging Two-photon microscopy Self-organization Column Reciprocal inhibition
We thank K. Fukunaga for the generous gift of rabbit pan CaMKII antiserum and B. Bell for language assistance. This work was supported by a Grant-in-Aid for Scientific Research (No. 25250001 to HY), a Grant-in-Aid for Scientific Research on Innovative Areas (Adaptive Circuit Shift: No. 15H01413 to HY; Comprehensive Brain Science Network; Platforms for Advanced Technologies and Research Resources: No. 16H06276 to HB) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan: http://www.jsps.go.jp/english/e-grants/grants01.html as well as JST, Strategic International Collaborative Research Program, SICORP (to HY): http://www.jst.go.jp/inter/english/sicorp/index.html and CREST (JPMJCR1656 to AY).
KK contributed to conceiving, designing and performing the experiments. KK and HY contributed to data analysis. MI, SC, HB, AY and TI contributed by providing reagents, materials, and analysis tools. KK and HY contributed to data interpretation and manuscript writing. All authors approved the final version of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
Statement on the welfare of animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.
- 9.Lee SH, Kwan AC, Zhang S, Phoumthipphavong V, Flannery JG, Masmanidis SC, Taniguchi H, Huang ZJ, Zhang F, Boyden ES, Deisseroth K, Dan Y (2012) Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488:379–383. https://doi.org/10.1038/nature11312 CrossRefGoogle Scholar
- 13.Markram H, Muller E, Ramaswamy S, Reimann MW, Abdellah M, Sanchez CA, Ailamaki A, Alonso-Nanclares L, Antille N, Arsever S, Kahou GA, Berger TK, Bilgili A, Buncic N, Chalimourda A, Chindemi G, Courcol JD, Delalondre F, Delattre V, Druckmann S, Dumusc R, Dynes J, Eilemann S, Gal E, Gevaert ME, Ghobril JP, Gidon A, Graham JW, Gupta A, Haenel V, Hay E, Heinis T, Hernando JB, Hines M, Kanari L, Keller D, Kenyon J, Khazen G, Kim Y, King JG, Kisvarday Z, Kumbhar P, Lasserre S, Le Bé JV, Magalhães BR, Merchán-Pérez A, Meystre J, Morrice BR, Muller J, Muñoz-Céspedes A, Muralidhar S, Muthurasa K, Nachbaur D, Newton TH, Nolte M, Ovcharenko A, Palacios J, Pastor L, Perin R, Ranjan R, Riachi I, Rodríguez JR, Riquelme JL, Rössert C, Sfyrakis K, Shi Y, Shillcock JC, Silberberg G, Silva R, Tauheed F, Telefont M, Toledo-Rodriguez M, Tränkler T, Van Geit W, Díaz JV, Walker R, Wang Y, Zaninetta SM, DeFelipe J, Hill SL, Segev I, Schürmann F (2015) Reconstruction and simulation of neocortical microcircuitry. Cell 163:456–492. https://doi.org/10.1016/j.cell.2015.09.029 CrossRefGoogle Scholar
- 16.Kawashima T, Kitamura K, Suzuki K, Nonaka M, Kamijo S, Takemoto-Kimura S, Kano M, Okuno H, Ohki K, Bito H (2013) Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE. Nat Methods 10:889–895. https://doi.org/10.1038/nmeth.2559 CrossRefGoogle Scholar
- 17.Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O’Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–178. https://doi.org/10.1038/nature10360 CrossRefGoogle Scholar
- 27.Oertner TG, Helmchen F, de Lecea L, Beck H, Konnerth A, Kaupp B, Knöpfel T, Yawo H, Häusser M (2013) Optogenetic analysis of mammalian neural circuits. In: Hegemann P, Sigrist S (eds) Optogenetics, Dahlem Workshop Reports. De Gruyter, Berlin, pp 109–126Google Scholar
- 29.Aravanis AM, Wang LP, Zhang F, Meltzer LA, Mogri MZ, Schneider MB, Deisseroth K (2007) An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng 4:S143–S156. https://doi.org/10.1088/1741-2560/4/3/S02 CrossRefGoogle Scholar
- 38.Ronzitti E, Conti R, Zampini V, Tanese D, Foust AJ, Klapoetke N, Boyden ES, Papagiakoumou E, Emiliani V (2017) Submillisecond optogenetic control of neuronal firing with two-photon holographic photoactivation of Chronos. J Neurosci 37:10679–10689. https://doi.org/10.1523/JNEUROSCI.1246-17.2017 CrossRefGoogle Scholar
- 52.Oberlaender M, Boudewijns ZS, Kleele T, Mansvelder HD, Sakmann B, de Kock CP (2011) Three-dimensional axon morphologies of individual layer 5 neurons indicate cell type-specific intracortical pathways for whisker motion and touch. Proc Natl Acad Sci USA 108:4188–4193. https://doi.org/10.1073/pnas.1100647108 CrossRefGoogle Scholar