Central amygdala circuit dynamics underlying the benzodiazepine anxiolytic effect

Griessner J, Pasieka M, Böhm V, Grössl F, Kaczanowska J, Pliota P, Kargl D, Werner B, Kaouane N, Strobelt S, Kreitz S, Heß A, Haubensak W (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Molecular Psychiatry Springer Nature

Book Volume: 26

Pages Range: 534-544

Journal Issue: 2

DOI: 10.1038/s41380-018-0310-3

Abstract

Benzodiazepines (BZDs) have been a standard treatment for anxiety disorders for decades, but the neuronal circuit interactions mediating their anxiolytic effect remain largely unknown. Here, we find that systemic BZDs modulate central amygdala (CEA) microcircuit activity to gate amygdala output. Combining connectome data with immediate early gene (IEG) activation maps, we identified the CEA as a primary site for diazepam (DZP) anxiolytic action. Deep brain calcium imaging revealed that brain-wide DZP interactions shifted neuronal activity in CEA microcircuits. Chemogenetic silencing showed that PKCδ⁺/SST⁻ neurons in the lateral CEA (CEAl) are necessary and sufficient to induce the DZP anxiolytic effect. We propose that BZDs block the relay of aversive signals through the CEA, in part by local binding to CEAl SST⁺/PKCδ⁻ neurons and reshaping intra-CEA circuit dynamics. This work delineates a strategy to identify biomedically relevant circuit interactions of clinical drugs and highlights the critical role for CEA circuitry in the pathophysiology of anxiety.

Authors with CRIS profile

Sandra Strobelt Lehrstuhl für Pharmakologie und Toxikologie Silke Kreitz Lehrstuhl für Pharmakologie und Toxikologie Andreas Heß Medizinische Fakultät

Involved external institutions

Forschungsinstitut für Molekulare Pathologie / Research Institute of Molecular Pathology (IMP)

Austria (AT) Vienna Biocenter VBC

Austria (AT)

How to cite

APA:

Griessner, J., Pasieka, M., Böhm, V., Grössl, F., Kaczanowska, J., Pliota, P.,... Haubensak, W. (2021). Central amygdala circuit dynamics underlying the benzodiazepine anxiolytic effect. Molecular Psychiatry, 26(2), 534-544. https://dx.doi.org/10.1038/s41380-018-0310-3

MLA:

Griessner, Johannes, et al. "Central amygdala circuit dynamics underlying the benzodiazepine anxiolytic effect." Molecular Psychiatry 26.2 (2021): 534-544.

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