Fear conditioning is widely used to assess associative memory in mice, yet percent freezing conflates memory with baseline locomotor and anxiety-related traits. A systematic survey of recent studies (2020–2025) found that fewer than 1% statistically integrate locomotor activity into freezing analyses. Here, we address this gap using a large-scale dataset of >10,000 mice across >160 comparisons, including genetic mutations, pharmacological interventions and aging, tested in 15 standardized behavioral paradigms. Conventional freezing scores covaried strongly with general locomotor activity, obscuring memory-related phenotypes. Multiple factor analysis identified two principal behavioral dimensions, locomotor activity and learning/memory: conventional freezing aligned with the locomotor dimension, whereas freezing subtraction and the activity suppression ratio mapped onto the memory dimension and improved detection of synaptic plasticity phenotypes. These analyses show that baseline locomotor normalization is essential for interpreting fear conditioning as a memory assay and provide an open framework for selecting and reporting locomotor-normalized metrics.
Daiki X. Sato, M. M. Chatzigiannis, Hirotaka Shoji et al.· bioRxiv· 0 citations
Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulators of gene expression, yet their interactions with transcription factors (TFs) remain poorly understood. While previous studies have identified lncRNA-TF associations in specific biological contexts, a broader perspective on their evolutionary and functional relationships remains necessary. In this study, we systematically analyze the proximity and co-expression patterns of lncRNAs and TF-encoding genes in humans. We reveal consistent spatial associations and tissue-specific co-expression between lncRNAs and TFs using genome-wide annotations and transcriptomic data. Time-series analysis reveals interesting, but not definitive, dynamic correlations suggesting potential functional interactions. Additionally, our evolutionary analysis identified conserved pairs across species, particularly those related to developmental processes such as eye development, highlighting possible avenues for further investigation in evolutionary and developmental contexts. In summary, our findings provide new insights into the spatial and co-expression associations between lncRNAs and TF genes, and suggest directions for future research on the potential roles of lncRNAs in gene regulatory networks.
T. Yamada, Martin Loza, I. Hatada et al.· Scientific Reports· 0 citations
