Brain-wide neuron quantification toolkit reveals strong sexual dimorphism in the evolution of fear memory

Year: 2023

Authors: Franceschini A., Mazzamuto G., Checcucci C., Chicchi L., Fanelli D., Costantini I., Passani MB., Silva BA., Pavone FS., Silvestri L.

Autors Affiliation: Univ Florence, European Lab Nonlinear Spect LENS, Sesto Fiorentino, Italy; Univ Florence, Dept Phys & Astron, Sesto Fiorentino, Italy; Natl Res Council CNR INO, Natl Inst Opt, Sesto Fiorentino, Italy; Univ Florence, Dept Informat Engn DINFO, Florence, Italy; Univ Florence, Dept Biol, Florence, Italy; Univ Florence, Dept Hlth Sci, Florence, Italy; Natl Res Council Italy, Inst Neurosci, Milan, Italy; IRCCS Human Res Hosp, Lab Circuits Neurosci, Milan, Italy.

Abstract: Fear responses are functionally adaptive behaviors that are strengthened as memories. Indeed, detailed knowledge of the neural circuitry modulating fear memory could be the turning point for the comprehension of this emotion and its pathological states. A comprehensive understanding of the circuits mediating memory encoding, consolidation, and retrieval presents the fundamental technological challenge of analyzing activity in the entire brain with single-neuron resolution. In this context, we develop the brain-wide neuron quantifi-cation toolkit (BRANT) for mapping whole-brain neuronal activation at micron-scale resolution, combining tissue clearing, high-resolution light-sheet microscopy, and automated image analysis. The robustness and scalability of this method allow us to quantify the evolution of activity patterns across multiple phases of memory in mice. This approach highlights a strong sexual dimorphism in recruited circuits, which has no counterpart in the behavior. The methodology presented here paves the way for a comprehensive char-acterization of the evolution of fear memory.

Journal/Review: CELL REPORTS

Volume: 42 (8)      Pages from: 112908-1  to: 112908-20

More Information: & nbsp;The authors are thankful to Antonino Paolo di Giovanna, Barbara Rani, and Alessia Costa, University of Florence, for lab support in setting up protocols with tissues and animals. This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements nos. 785907 (HBP SGA2) , 945539 (HBP SGA3) , and 654148 (Laserlab-Europe) . This work was supported by #NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR) , National Recovery and Resilience Plan (NRRP) , project MNESYS (PE0000006) – A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022) . This project was supported by the Italian Ministry for Foreign Affairs and International Cooperation within the program for joint strategic pro- jects between Italy and United States of America (US23GR05) . The project has also been supported by the Italian Ministry for Education, University, Research through projects CNR-FOE-LENS-2021, Flag-era HA-ction, Smart Brain, and by Fondazione CR Firenze (private foundation) . The laboratory of B.A.S. is supported by the Cariplo Foundation (Cariplo Giovani 2020- 3632) . Part of this work was performed in the framework of the Proof of Concept Studies for the ESFRI research infrastructure project Euro- BioImaging at the LENS PCS facility.
KeyWords: Fos Expression; C-fos; Amygdala; Stress; Organization; Interrogation; Mechanisms; Microscopy; Centrality; Resolution
DOI: 10.1016/j.celrep.2023.112908

Citations: 2
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