Brain-wide neuron quantification toolkit reveals strong sexual dimorphism in the evolution of fear memory
Alessandra Franceschini,
Giacomo Mazzamuto,
Curzio Checcucci,
Lorenzo Chicchi,
Duccio Fanelli,
Irene Costantini,
Maria Beatrice Passani,
Bianca Ambrogina Silva,
Francesco Saverio Pavone,
Ludovico Silvestri
Affiliations
Alessandra Franceschini
European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy; Corresponding author
Giacomo Mazzamuto
European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy; National Institute of Optics - National Research Council (CNR-INO), Sesto Fiorentino, Italy
Curzio Checcucci
Department of Information Engineering (DINFO), University of Florence, Florence, Italy
Lorenzo Chicchi
Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy
Duccio Fanelli
Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy
Irene Costantini
European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department of Biology, University of Florence, Florence, Italy
Maria Beatrice Passani
Department of Health Sciences, University of Florence, Florence, Italy
Bianca Ambrogina Silva
National Research Council of Italy, Institute of Neuroscience, Milan, Italy; IRCCS Humanitas Research Hospital, Lab of Circuits Neuroscience, Rozzano, Milan, Italy
Francesco Saverio Pavone
European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy; National Institute of Optics - National Research Council (CNR-INO), Sesto Fiorentino, Italy
Ludovico Silvestri
European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy; Department of Physics and Astronomy, University of Florence, Sesto Fiorentino, Italy; National Institute of Optics - National Research Council (CNR-INO), Sesto Fiorentino, Italy; Corresponding author
Summary: 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 quantification 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 characterization of the evolution of fear memory.
