Supplementary file 1_Selective behavioral and prefrontal transcriptomic correlates of acute clozapine exposure in socially isolated mice.pdf

Social isolation rearing produces schizophrenia-relevant behavioral abnormalities and permits joint evaluation of housing and drug exposure.</p>Objective<p>To characterize behavioral and prefrontal transcriptomic correlates of an acute clozapine challenge in socially isolated mice, reassess previously prioritized Ank3 and Nrxn1, and provide external cellular-context hypotheses for candidate genes.</p>Methods<p>Male C57BL/6J mice were evaluated in a four-group housing-by-drug design using open-field, novel-object recognition and prepulse-inhibition tests.

For a reproducible transcriptome-wide audit, 11 publicly retrievable prefrontal cortex libraries were re-quantified using a factorial DESeq2 model with false-discovery-rate control. Historical pairwise prioritization, network analysis, machine-learning screening, molecular docking and molecular-dynamics simulations were treated as exploratory analyses. Adult wild-type prefrontal cortex single-cell RNA-seq data were used for cellular localization, CellChat analysis and virtual knockout, whereas an embryonic cortical reference was used separately for CellOracle transcription-factor perturbation.</p>Results<p>Acute clozapine showed its clearest behavioral effect on isolation-associated hyperlocomotion, whereas recognition memory was not improved and prepulse-inhibition results varied by stimulus intensity.