Connectomics is the study of biological neural networks at synaptic resolution. The resulting wiring diagrams teach us how information is processed in animal brains, including perception and behaviour.
However, connectomes have always been static snapshots where dynamics remain hidden. Evidence is accumulating for the brain’s code to be in constant flux, which means that fundamental features of biological computation remain inaccessible to study via static wiring diagrams.
Until recently, connectomics relied exclusively on electron microscopy. We are now using expansion microscopy for an optical approach to connectomics. This allows us to integrate a molecular readout dimension via fluorescence-based tools.
Using these tools will allow us to both map the brain’s circuits and overlay information on the plasticity states of each synaptic connection. This information is critical to understanding the history of each connection across behavioural timescales, from weeks to seconds, including the memory of learned behaviours. The aim of this project is to adapt and build molecular tools that allow the readout of dynamics in connectomes using optical approaches and to use those tools to build maps of adaptive neural networks recapitulating animal behaviour.
Relevant Reading
Light-microscopy-based connectomic reconstruction of mammalian brain tissueTavakoli MR, Lyudchik J, Januszewski M, Vistunou V, Agudelo Dueñas N, Vorlaufer J, Sommer C, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl JGNature 642(8067): 398-410 (2025)
Combinatorial protein barcodes enable self-correcting neuron tracing with nanoscale molecular contextPark SY, Sheridan A, An B, Jarvis E, Lyudchik J, Patton W, Axup JY, Chan SW, Damstra HGJ, Leible D, Leung KS, Magno CA, Meeran A, Michalska JM, Rieger F, Wang C, Wu M, Church GM, Funke J, Huffman T, Leeper KGC, Truckenbrodt S, Winnubst J, Kornfeld JMR, Boyden ES, Rodriques SG, Payne ACbioRxiv: (2025) preprint
Neuronal wiring diagram of an adult brainDorkenwald S, Matsliah A, Sterling AR, Schlegel P, Yu S, McKellar CE, Lin A, Costa M, Eichler K, Yin Y, Silversmith W, Schneider-Mizell C, Jordan CS, Brittain D, Halageri A, Kuehner K, Ogedengbe O, Morey R, Gager J, Kruk K, Perlman E, Yang R, Deutsch D, Bland D, Sorek M, Lu R, Macrina T, Lee K, Bae JA, Mu S, Nehoran B, Mitchell E, Popovych S, Wu J, Jia Z, Castro MA, Kemnitz N, Ih D, Bates AS, Eckstein N, Funke J, Collman F, Bock DD, Jefferis GSXE, Seung HS, Murthy M, Lenizo Z, Burke AT, Willie KP, Serafetinidis N, Hadjerol N, Willie R, Silverman B, Ocho JA, Bañez J, Candilada RA, Kristiansen A, Panes N, Yadav A, Tancontian R, Serona S, Dolorosa JI, Vinson KJ, Garner D, Salem R, Dagohoy A, Skelton J, Lopez M, Capdevila LS, Badalamente G, Stocks T, Pandey A, Akiatan DJ, Hebditch J, David C, Sapkal D, Monungolh SM, Sane V, Pielago ML, Albero M, Laude J, dos Santos M, Vohra Z, Wang K, Gogo AM, Kind E, Mandahay AJ, Martinez C, Asis JD, Nair C, Patel D, Manaytay M, Tamimi IFM, Lim CA, Ampo PL, Pantujan MD, Javier A, Bautista D, Rana R, Seguido J, Parmar B, Saguimpa JC, Moore M, Pleijzier MW, Larson M, Hsu J, Joshi I, Kakadiya D, Braun A, Pilapil C, Gkantia M, Parmar K, Vanderbeck Q, Salgarella I, Dunne C, Munnelly E, Kang CH, Lörsch L, Lee J, Kmecova L, Sancer G, Baker C, Joroff J, Calle S, Patel Y, Sato O, Fang S, Salocot J, Salman F, Molina-Obando S, Brooks P, Bui M, Lichtenberger M, Tamboboy E, Molloy K, Santana-Cruz AE, Hernandez A, Yu S, Diwan A, Patel M, Aiken TR, Morejohn S, Koskela S, Yang T, Lehmann D, Chojetzki J, Sisodiya S, Koolman S, Shiu PK, Cho S, Bast A, Reicher B, Blanquart M, Houghton L, Choi H, Ioannidou M, Collie M, Eckhardt J, Gorko B, Guo L, Zheng Z, Poh A, Lin M, Taisz I, Murfin W, Díez S, Reinhard N, Gibb P, Patel N, Kumar S, Yun M, Wang M, Jones D, Encarnacion-Rivera L, Oswald A, Jadia A, Erginkaya M, Drummond N, Walter L, Tastekin I, Zhong X, Mabuchi Y, Figueroa Santiago FJ, Verma U, Byrne N, Kunze E, Crahan T, Margossian R, Kim H, Georgiev I, Szorenyi F, Adachi A, Bargeron B, Stürner T, Demarest D, Gür B, Becker AN, Turnbull R, Morren A, Sandoval A, Moreno-Sanchez A, Pacheco DA, Samara E, Croke H, Thomson A, Laughland C, Dutta SB, de Antón PGA, Huang B, Pujols P, Haber I, González-Segarra A, Choe DT, Lukyanova V, Mancini N, Liu Z, Okubo T, Flynn MA, Vitelli G, Laturney M, Li F, Cao S, Manyari-Diaz C, Yim H, Duc Le A, Maier K, Yu S, Nam Y, Bąba D, Abusaif A, Francis A, Gayk J, Huntress SS, Barajas R, Kim M, Cui X, Sterne GR, Li A, Park K, Dempsey G, Mathew A, Kim J, Kim T, Wu G, Dhawan S, Brotas M, Zhang C, Bailey S, Del Toro A, Yang R, Gerhard S, Champion A, Anderson DJ, Behnia R, Bidaye SS, Borst A, Chiappe E, Colodner KJ, Dacks A, Dickson B, Garcia D, Hampel S, Hartenstein V, Hassan B, Helfrich-Forster C, Huetteroth W, Kim J, Kim SS, Kim YJ, Kwon JY, Lee WC, Linneweber GA, Maimon G, Mann R, Noselli S, Pankratz M, Prieto-Godino L, Read J, Reiser M, von Reyn K, Ribeiro C, Scott K, Seeds AM, Selcho M, Silies M, Simpson J, Waddell S, Wernet MF, Wilson RI, Wolf FW, Yao Z, Yapici N, Zandawala MNature 634(8032): 124-138 (2024)
