Extended Data Fig. 10: TBS-induced LTP in CA1 oriens/alveus (O/A) somatostatin-expressing interneurons exerts a more robust suppression of TA-CA1 LTP in Eif2a cKI^Sst mice.

a–c, Schematic of experimental setup in acute hippocampal slices: Temporoammonic afferents from the entorhinal cortex were stimulated by a weak TBS (wTBS) in presence or absence of prior TBS in CA1 oriens/alveus (O/A) region and fEPSPs were recorded in stratum lacunosum-moleculare of CA1. d, In Sst-Cre⁺ hippocampal slices, TBS in CA1-O/A region suppresses LTP of TA-CA1 field excitatory postsynaptic potentials (fEPSPs) when compared to slices with No-TBS in CA1-O/A region. e, In Eif2a cKI^Sst hippocampal slices, TBS in CA1-O/A region also reduces TA-LTP relative to slices with No-TBS in CA1-O/A region. f, Summary plots of normalized LTP magnitude in TA-CA1 pathway. TBS at CA1-O/A supress TA-CA1 pathway in Sst-Cre⁺ (F _{3, 24} = 11.85; n = 6, 8, points represent individual mice) and Eif2a cKI^Sst (F _{3, 24} = 11.85; n = 7, 7, points represent individual mice). However, the magnitude of suppression is larger in Eif2a cKI^Sst than in Sst-Cre⁺ mice (F _{3, 24} = 11.85; n = 8, 7, points represent individual mice). g, Reduction of p-eIF2α in CAMK2α-expressing excitatory neurons facilitates L-LTP and excitatory synaptic transmission (amplitude and frequency of mEPSCs), reduces inhibitory synaptic transmission (frequency of mIPSCs) and enhances memory consolidation (fear conditioning). h, Ablation of p-eIF2α in parvalbumin-expressing neurons causes a reduction in mEPSC amplitude without affecting threshold for L-LTP induction or consolidation of fear memory. i, Depletion of p-eIF2α in somatostatin-expressing neurons facilitates L-LTP and consolidation of fear memory by reducing the amplitude of mIPSCs in pyramidal neurons and enhancing suppression of LTP in the TA pathway. Data are presented as mean ± s.e.m. in d–f. p-values by one-way ANOVA followed by Tukey’s multiple comparisons post hoc test in f are indicated.

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