Fig. 1. Som⁺ interneurons in CA1 are required for learning hf-CFC.

(A) Schematic of hf-CFC task. A head-fixed mouse on a treadmill is exposed to contexts (CS) defined by distinct sets of multisensory stimuli. We used air puffs as the US and suppression of water-licking as a measure of learned fear (CR). The two distinct contexts used in this study are described at right. (B) Behavioral data from an example mouse over the hf-CFC paradigm. Conditioned (CtxC) and neutral (CtxN) contexts are each presented once a day, and lick rate is assessed during the 3-min context. (C) Summary data for 19 mice [two-way analysis of variance (ANOVA), context x session, F(_1,19) = 9.34, P < 0.01]. Mice showed a selective decrease in mean lick rate between habituation and recall in CtxC but not CtxN (paired sign tests). (D) Viral expression of PSAM^L141F-GlyR in the amygdala or dorsal CA1, revealed by α-bungarotoxin-Alexa647 immunostaining. All injections were bilateral; for simplicity, only one hemisphere is shown. Image at top left is from the Allen Brain Atlas. (E) Summary data for mice injected with PSEM⁸⁹ systemically 15 min before the conditioning session in CtxC (day 2 of hf-CFC paradigm). Learning is assessed by the percentage of lick-rate decrease in the CtxC recall session (day 3) relative to the mean lick rate in all sessions. Mice expressing PSAM^L141F-GlyR in amygdala cells (Amyg., n = 6 mice), dorsal CA1 cells (CA1, n = 5 mice), or CA1 Som⁺ interneurons (CA1-Som⁺, n = 8 mice) showed impaired learning compared with mice not expressing PSAM^L141F-GlyR (No PSAM, n = 11 mice), whereas mice expressing PSAM^L141F-GlyR in CA1 Pvalb⁺ interneurons (CA1-Pvalb⁺, n = 4 mice) did not. Comparisons are Mann-Whitney U tests. Error bars, mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001.