Neuronal circuits of anxiety – Janos Fuzik group

Research focus

The periaqueductal gray matter (PAG) is a midbrain structure processing threatful and panicogenic stimuli and involved in the regulation of autonomic functions. Direct stimulation of PAG neurons in humans and in rodents evokes panic-like behavior and associated autonomic responses. However, the identity of PAG neurons and the circuit motifs process the threat- and panic-related information is poorly understood.

We use viral labeling to study anatomy of projections and electrophysiology, Patch-Seq, and high-throughput voltage imaging combined with RNA-transcriptomics (Voltage-Seq) to dissect the PAG networks in naïve and panic-like neuronal circuits; we use in vivo mouse optogenetics and behavior to induce and validate panic-like states.

Our research has a special angle on sex-differences as this factor strongly determines the susceptibility to panic disorder. We identify the neuronal types and circuit motifs with pioneering techniques to detect molecular and physiological changes in male and female circuits of panic-like state.

Research support

• Åke Wibergs Stiftelse, Sweden
• BBRF NARSAD Young Investigator Grant, USA
• Jeansson Stiftelse, Sweden
• Swedish Brain Foundation, Sweden
• The Strategic Research Area Neuroscience (StratNeuro), Sweden
• Vetenskapsrådet (The Swedish Research Council), Sweden
• Karolinska Institutet, Sweden
• Thurings Stiftesle, Sweden

Selected publications

All-optical voltage imaging-guided postsynaptic single-cell transcriptome profiling with Voltage-Seq. (accepted for publication). Csillag V, Noble JC, Calvigioni D, Reinius B, Fuzik J
Nature Protocols (2024)

Voltage-Seq: all-optical postsynaptic connectome-guided single-cell transcriptomics.
Csillag V, Bizzozzero MH, Noble JC, Reinius B, Fuzik J
Nat Methods 2023 Sep;20(9):1409-1416

Esr1+ hypothalamic-habenula neurons shape aversive states.
Calvigioni D, Fuzik J, Le Merre P, Slashcheva M, Jung F, Ortiz C, Lentini A, Csillag V, Graziano M, Nikolakopoulou I, Weglage M, Lazaridis I, Kim H, Lenzi I, Park H, Reinius B, Carlén M, Meletis K
Nat Neurosci 2023 Jul;26(7):1245-1255

Brain-wide genetic mapping identifies the indusium griseum as a prenatal target of pharmacologically unrelated psychostimulants.
Fuzik J, Rehman S, Girach F, Miklosi AG, Korchynska S, Arque G, Romanov RA, Hanics J, Wagner L, Meletis K, Yanagawa Y, Kovacs GG, Alpár A, Hökfelt TGM, Harkany T
Proc Natl Acad Sci U S A 2019 Dec;116(51):25958-25967

Integration of electrophysiological recordings with single-cell RNA-seq data identifies neuronal subtypes.
Fuzik J, Zeisel A, Máté Z, Calvigioni D, Yanagawa Y, Szabó G, Linnarsson S, Harkany T
Nat Biotechnol 2016 Feb;34(2):175-183