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. 2023 Jul 27;28(8):3444–3458. doi: 10.1038/s41380-023-02197-7

Fig. 3. Loss of dendritic spines in the PrL is detrimental to working memory performance in ELA mice.

Fig. 3

A–E Defective working memory in ELA mice. The spontaneous alternation (%) in a T-maze task was reduced in a cohort of Thy1-YFPH ELA mice compared to controls (t22 = 8.24, **P  <  0.01) (A). Choice latency of these mice in both groups displayed an increased trend across the trials. ELA mice spent longer times to visit a goal arm during the last two trials (T5 and T6) (two-way RM ANOVA, main effect of ELA: F1,22 = 21.82; *P < 0.05, **P < 0.01) (B). Reduced rewarded alternation (%) in a cohort of C57 ELA mice versus their controls (t22 = 5.00, **P  <  0.01), which was detected via a T-maze based win-shift task (C). When C57 ELA mice were compared to controls, no difference was observed in the time spent at the center in an open-field test (t22 = 0.43, P  =  0.67) (D) or the time immobile in a swim stress test (t22 = 0.16, P  =  0.87) (E). F–H YFP-labeled spines on PrL pyramidal cells. Representative confocal image from a Thy1-YFPH control mouse to clarify the analyzed dendritic segments in the PrL. The boxed segments in layers II-III and V-VI were magnified in G to present thin spines (arrows) and mushroom-type spines (arrowheads) for comparisons with an ELA mouse (H). Scale bars = 100 µm (F) and 8 µm (G, H). I–K Quantitative analysis. Spine loss was apparent in layers II-III and V-VI in ELA mice (F1,12 = 40.30; **P < 0.01). Both mushroom-type and thin spines were decreased in ELA mice versus controls (F1,22 = 13.66 and 51.40 for mushroom-type and thin spines, respectively; *P < 0.05, **P < 0.01). L, M Positive correlations were observed between spontaneous alternation in a T-maze and the density of total spines in layers II-III (Pearson r = 0.68, P < 0.05) and V-VI (r = 0.63, P < 0.05). When dendritic spines were classified as mushroom-type and thin spines, and ELA mice and controls were analyzed separately, a positive correlation between thin spines and spontaneous alternation was observed in both the ELA group (r = 0.65 and 0.70 in II-III and V-VI, respectively, P < 0.05) and the control group (r = 0.61 and 0.59 in II-III and V-VI, respectively, P < 0.05) (M).