Slitrk5 deficiency preserves reversal learning but alters orbitofrontal-striatal signaling and task-related responding in mice.

Authors

Ole Borup Svendsen, Hui Shi, Humam Ahmed Hamdoun, Lí Deng, Jens Midtgaard, Francis S Lee, Jens Randel Nyengaard, Ning-Long Xu

Published in

Behavioural brain research. Pages 116441. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Obsessive-compulsive disorder (OCD) is a debilitating condition associated with repetitive behaviors and cognitive inflexibility, often linked to abnormalities in cortico-striato-thalamo cortical (CSTC) circuitry. Although the Slitrk5 knockout (Slitrk5^-/-, KO) mouse has been proposed as an OCD-related model, it remains unclear how Slitrk5 deficiency influences adaptive decision making, task-related behavioral organization, and orbitofrontal-dorsomedial striatum (OFC-DMS) signaling during reversal learning. To address this, Slitrk5^-/- and wild-type (WT) mice were examined using probabilistic reversal-learning paradigms combined with licking-behavior analyses, fiber photometry recordings optogenetic inhibition of OFC-DMS projections, and open-field assessment. Across paradigms, Slitrk5^-/- mice displayed largely preserved reversal-learning performance and adapted to changing reward contingencies similarly to WT mice. However, genotype-dependent differences emerged in how licking behavior was organized across behavioral epochs and reward contingencies, indicating altered anticipatory, choice-related, and reward-associated responding during task performance. Fiber photometry recordings further identified altered OFC-striatal signaling in Slitrk5^-/- mice across anticipatory and reward-associated behavioral periods. In contrast, optogenetic inhibition of OFC-DMS projections produced no detectable effects on reversal-learning performance or licking behavior. Open-field assessment revealed age-dependent alterations in locomotor and exploratory behavior together with progressive grooming-related lesion development. Together, these findings demonstrate selective alterations in task-related behavioral organization and OFC-striatal signaling despite preserved reversal-learning performance in Slitrk5^-/- mice, highlighting the heterogeneous behavioral and neural expression associated with corticostriatal dysfunction across OCD-related phenotypes.

PMID:
42603634
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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