Rogerson, L. | bioRxiv Science

bioRxiv2026

Lasting aversive consequences of a single dose of 4-hydroxytamoxifen

4-hydroxytamoxifen (4-OHT) is commonly used to facilitate activity-dependent recombination in neurons. Here we show that one dose of 4-OHT devalues alcohol, contexts, and tastants, indicating that experimental designs using 4-OHT should control for its aversiveness. Further, reactivation of 4-OHT-responsive neurons causes conditioned taste avoidance. An activity screen coupled with graph theoretical analysis identifies candidate brain areas mediating these effects. We suggest these areas could be therapeutic targets for treating addiction.

neuroscience↗

bioRxiv2025

Two-timepoint assays of neural responses increase the sensitivity and specificity of single-cell whole-brain activity screens

Current approaches for surveying whole brains for neurons activated during a particular state typically rely on immediate early gene (IEG) expression. However, IEG expression is variable across subjects and brain areas, demanding large sample sizes. Further, it cannot determine if the same or different neurons respond to two events. To overcome these issues, we present a whole-brain screening method utilizing transgenic mice to label neurons activated at two timepoints. An imaging and analysis pipeline surveys activity in ~500 brain areas in different conditions. Compared to IEG methods, this approach reduces required sample sizes and enhances sensitivity and specificity. Finally, graph theoretical analyses are utilized to identify key circuit nodes - brain areas whose activity correlates with activity in other areas in a state-dependent manner. We validate this method by surveying whole-brain activity during hunger and satiety, and by investigating neural circuits activated by the GLP1 agonist semaglutide used to treat obesity.

neuroscience↗