- Slitrk5 knockout mice show preserved probabilistic reversal-learning performance, adapting to changing reward contingencies similarly to wild-type mice.
- Slitrk5 deficiency alters task-related behavioural organisation, modifying anticipatory, choice-related and reward-associated licking across behavioural epochs and contingencies.
- Orbitofrontal to dorsomedial striatum signalling is altered during anticipatory and reward periods, while optogenetic OFC-DMS inhibition did not affect performance.
Behav Brain Res. 2026 Aug 15:116441. doi: 10.1016/j.bbr.2026.116441. Online ahead of print.
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 | DOI:10.1016/j.bbr.2026.116441
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