Rodent strain differences in sensory function and gating: implications for cognitive phenotyping and brain disease models

Rodent strain differences are well established, yet their implications for sensory-dependent cognitive phenotyping are not always adequately distinguished from effects of substrain divergence, experimental environment, or disease-related manipulations. This review synthesizes evidence that auditory and visual function, sensory and sensorimotor gating, and task-dependent behavioral strategies shape how cognitive phenotypes are expressed and interpreted across commonly used mouse and rat populations. Direct comparative studies reveal strain- and age-dependent variation in auditory thresholds, visual acuity, prepulse inhibition, habituation, and auditory evoked responses. These differences can affect access to task-relevant stimuli and the interpretation of behavioral measures without necessarily indicating deficits in learning or memory. We further examine strain-related differences in hippocampal synaptic plasticity, GABAergic inhibition, interneuron composition, and network oscillations, while distinguishing ex vivo network phenotypes from demonstrated mechanisms in behaving animals. Thalamic reticular nucleus–auditory thalamic and mediodorsal thalamus–prefrontal cortex pathways are considered plausible candidate circuit substrates; direct evidence that they mediate inter-strain cognitive differences remains limited. Studies of genetically modified and brain disease models additionally show that genetic background can amplify, attenuate, or leave unchanged mutation-associated phenotypes, making both strong and limited background effects informative. Within an integrative sensory–cognitive gating framework, we propose a strain-informed approach emphasizing precise population identification, task-relevant sensory assessment, appropriate genetic controls, complementary behavioral readouts, and background validation proportional to the intended scope of inference. This framework serves as a guide to interpretation rather than an established causal pathway, with the aim of improving reproducibility, mechanistic interpretation, and the translational relevance of rodent models.