title: Display of individuality in avoidance behavior and risk assessment of inbred mice.
abstract: Factors determining individuality are still poorly understood. Rodents are excellent model organisms to study individuality, due to a rich behavioral repertoire and the availability of well-characterized isogenic populations. However, most current behavioral assays for rodents have short test duration in novel test environments and require human interference, which introduce coercion, thereby limiting the assessment of naturally occurring individuality. Thus, we developed an automated behavior system to longitudinally monitor conditioned fear for assessing PTSD-like behavior in individual mice. The system consists of a safe home compartment connected to a risk-prone test compartment (TC). Entry and exploration of the TC is solely based on deliberate choice determined by individual fear responsiveness and fear extinction. In this novel ethological assay, C57BL/6J mice show homogeneous responses after shock exposure (innate fear), but striking variation in long-lasting fear responses based on avoidance and risk assessment (learned fear), including automated stretch-attend posture quantification. TC entry (retention) latencies after foot shock differed >24 h and the re-explored TC area differed >50% among inbred mice. Next, we compared two closely related C57BL/6 substrains. Despite substantial individual differences, previously observed higher fear of C57BL/6N vs. C57BL/6J mice was reconfirmed, whereas fear extinction was fast and did not differ. The observed variation in fear expression in isogenic mice suggests individual differences in coping style with PTSD-like avoidance. Investigating the assumed epigenetic mechanisms, with reduced interpretational ambiguity and enhanced translational value in this assay, may help improve understanding of personality type-dependent susceptibility and resilience to neuropsychiatric disorders such as PTSD.
authors.affiliation: Sylics BV Amsterdam, Netherlands ; Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands ; Department of Clinical Genetics, VU University Medical Center Amsterdam, Netherlands.
authors.forename: Torben
authors.initials: T
authors.lastname: Hager
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands ; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands.
authors.forename: René F
authors.initials: RF
authors.lastname: Jansen
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands ; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands.
authors.forename: Anton W
authors.initials: AW
authors.lastname: Pieneman
authors.affiliation: Biobserve GmbH St. Augustin, Germany.
authors.forename: Suriya N
authors.initials: SN
authors.lastname: Manivannan
authors.affiliation: Department of Zoology, Faculty of Life Sciences and Sagol School for Neuroscience, Tel Aviv University Tel Aviv, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Golani
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands ; Department of Clinical Genetics, VU University Medical Center Amsterdam, Netherlands.
authors.forename: Sophie
authors.initials: S
authors.lastname: van der Sluis
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands ; Department of Clinical Genetics, VU University Medical Center Amsterdam, Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands ; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam Amsterdam, Netherlands.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stiedl
keywords: animal model; behavioral phenotyping; fear conditioning; individuality; learning; memory; passive avoidance; post-traumatic stress disorder