Paper

Microbiopsy of living mouse brain for longitudinal molecular profiling

Fellouse, Loelia, Lingenberg, Alma, Hiver, Agnes, Hoyningen, Alexander, Marion-Poll, Lucile, Ramisch, Anna, Luscher, Christian

2026

Overview

This study presents a stereotactic microbiopsy technique for sampling defined brain regions in living mice, enabling transcriptomic and epigenomic analyses without sacrificing the animal. The method will allow pre-intervention tissue collection, making it possible to separate preexisting molecular differences from experience- or treatment-induced changes. We show that microbiopsies yield sufficient, high-quality RNA and chromatin for sequencing, with minimal tissue damage that largely resolves over time. The procedure uses standard stereotactic equipment and achieves reproducible spatial precision when the syringe is stabilised. This approach provides a practical framework for within-subject molecular comparisons, reducing animal use and enabling longitudinal profiling of the living mouse brain. It establishes a foundation for investigating how baseline molecular states influence later physiological or behavioural outcomes.Competing Interest StatementThe authors have declared no competing interest.Funder Information DeclaredSwiss National Science Foundation, 323630_214535Carigest SA

• Publisher: Cold Spring Harbor Laboratory Press
• Subject: Chromatin / Transcriptomics