Fig. 3: Learning-induced GluA2 turnover is more localized than following environmental enrichment.

a, Turnover measurement in a GluA2–HT knock-in mouse during learning of a new behavioral rule (new rule). b, Example experiment showing efficiency (number of rewards per number of cues licked) across five daily sessions. Turnover was assessed by pulse dye ligand (JFX₆₇₃-HTL) injection before new-rule and chase dye ligand (JF₅₅₂-HTL) perfusion after the final session. c, Behavioral efficiency comparison between baseline (green, unchanged) and new-rule (magenta, improved) groups (n = 7). d,e, Coronal sections showing pulse (magenta), chase (orange) and calculated GluA2–HT lifetime (fast turnover, green and blue; slower turnover, yellow) for new-rule (d) and baseline (e) conditions, highlighting CA1 differences. Example from (c) n = 7 animals. f, Experimental design for turnover measurement of GluA2–HT modulated by environmental enrichment (EE). g, Example coronal sections from control mice and after EE. A black asterisk indicates the lower lifetime of GluA2–HT in frontal cortical regions. Example from n = 9 animals. Color scale is the same as in d. h, Swanson flatmap⁷³ representation of mouse brain regions. Different colors represent different brain regions. i, Left: percentage change in GluA2–HT lifetime in baseline versus new rule. The largest effect is in CA1 (arrow). Middle: control versus EE groups. The largest effect is in the frontal pole (arrow). Right: percentage change in PSD-95–HT lifetime in control versus EE groups. j, Distribution of turnover changes across conditions. GluA2 learning (n = 442, median = 7.5%, 59.5% of brain regions with >5% change); GluA2 EE (n = 442, median = 14.3%, 94.8% >5%); PSD-95 EE (n = 580, median = 19.2%, 95.3% > 5%).