Swain, C. C. | bioRxiv Science

bioRxiv2026

Paw Preference in Rats Across Tests, Strains, Sex, and Age: A PRISMA-Compliant Systematic Review and Meta-Analysis

Paw preference in rats is widely used to study hemispheric lateralization, but many individual studies are underpowered and employ inconsistent methods, leading to conflicting reports of population-level bias. We conducted a PRISMA-compliant systematic review and meta-analysis to determine whether rats consistently display paw preference at the individual and population levels, and to evaluate the influence of behavioral test type, strain, sex, and age. Studies published between 1930 and 2025 were identified through PubMed, Google Scholar, and ScienceDirect. Data were extracted on strain, age, sex, behavioral paradigm, and paw-preference classification. Random-effects models were used to estimate pooled prevalence, with subgroup analyses for key variables. Forty studies (n = 1,609 rats) met inclusion criteria. At the individual level, 84% of rats displayed consistent paw preference (95% CI: 78-89%, p < 0.0001), demonstrating robust individual-level lateralization. However, population-level analyses showed no universal directional bias, right paw use occurred in 48% of rats (95% CI: 43-54%) and left paw use in 39% (95% CI: 34-44%). Ambidextrous classification thresholds were standardized across studies to ensure comparability. Subgroup analyses indicated modest strain- and test-dependent effects, with Sprague Dawley rats tending toward balanced paw use, while other strains showed slight rightward bias. Skilled-reaching tasks produced slightly stronger asymmetry than the Collins test. Sex- and age-related differences were subtle and inconsistent. Overall, rats exhibit reliable individual-level paw preference without species-wide directional asymmetry, distinguishing them from humans. Standardized testing protocols and balanced cohort designs will enhance reproducibility and translational relevance in lateralization research.

neuroscience↗

bioRxiv2024

Dynamic Changes in Chloride Homeostasis Coordinate Midbrain Inhibitory Network Activity during Reward Learning

The ability to associate environmental stimuli with positive outcomes is a fundamental form of learning. While extensive research has focused on the response profiles of midbrain dopamine neurons during associative learning, less is known about learning-mediated changes in the afferents that shape their responses. We demonstrate that during critical phases of learning, anion homeostasis in midbrain GABA neurons - a primary source of input to dopamine neurons - is disrupted due to downregulation of the chloride transporter KCC2. This alteration in GABA neurons preferentially impacted lateral mesoaccumbal dopamine pathways and was not observed after learning was established. At the network level, learning-mediated KCC2 downregulation was associated with enhanced synchronization between individual GABA neurons and increased dopamine responses to reward-related stimuli. Conversely, enhancing KCC2 function during learning reduced GABA synchronization, diminished relevant dopamine signaling, and prevented cue-reward associations. Thus, circuit-specific adaptations in midbrain GABA neurons are crucial for forming new reward-related behaviors.

neuroscience↗