Fig. 1: Reactivating mPFC social exploration-associated neurons enables social memory retrieval. | Communications Biology

Fig. 1: Reactivating mPFC social exploration-associated neurons enables social memory retrieval.

From: Social memory engram formation impairment in neuroligin-3 R451C knock-in mice is caused by disrupted prefrontal NMDA receptor-dependent potentiation

Fig. 1

A Experimental design for social-associated ensemble labeling. Doxycycline was taken off 24 h before the social test on Day 1 and placed back 24 h after it. B Left: Images of neurons in the mPFC activated during the social and control tests on Day 1. DAPI (blue) was used to label nuclei (scale bars, 50 and 200 μm). Cg1, cingulate cortex, area 1; PrL, prelimbic cortex; IL, infralimbic cortex. Right: The number of GFP-positive cells was significantly increased in the social group (Two-tailed Mann-Whitney test,p < 0.0001). C Left: Representative images of the prelimbic cortex (PrL) following dual exposure to social stimuli from the familiar mice (top) and novel mice (bottom). The cells activated by social stimuli on Day 1 were marked with GFP (green), while the c-Fos expression induced by social stimuli on Day 7 was revealed through immunostaining (red). Yellow arrows indicate cells co-labeled with GFP and c-Fos (GFP+ Fos+) (scale bar, 50 μm). Right: A greater number of neurons were reactivated (GFP+ Fos+) during social stimuli exposure from the familiar mice compared to those from novel mice (Two-tailed unpaired t test, t = 2.853, df = 16, p = 0.012). D Experimental design for activating social-associated ensemble. Doxycycline was taken off 24 h before the social test on Day 1 and placed back 24 h after it. Saline or DCZ was administered via intraperitoneal injection 90 min prior to the social behavior assessment on Day 7. E Top: Sample trace shows validation of virus by electrophysiological recording. Bottom: Representative images of neurons in the mPFC co-expressing hM3Dq and GFP (scale bar, 25 μm). F Representative heatmaps of three-chamber tests performed in saline- and DCZ-treated mice. G Sniffing time (left) and difference index (right) after chemogenetic reactivation of mPFC social exploration-associated neurons in three-chamber tests (Left: two-way ANOVA, Interaction: F(1, 46) = 4.911, p = 0.032; Drug: F(1, 46) = 0.050, p = 0.824; Familiar vs. Novel: F(1, 46) = 12.41, p = 0.001; Right: Two-tailed unpaired t test, t = 2.504, df = 23, p = 0.020). ± SEM. *p < 0.05, ***p < 0.001. n = number of mice.

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