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 cKISst 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 f EPSPs 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 (f EPSPs) when compared to slices with No-TBS in CA1-O/A region.
e, In Eif2a cKISst 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 = 1 1 .8 5; n = 6, 8, points represent individual mice) and
Eif2a cKISst (F (^) 3, 24 = 1 1 .8 5; n = 7, 7, points represent individual mice). However, the
magnitude of suppression is larger in Eif2a cKISst than in Sst-Cre+ mice
(F (^) 3, 24 = 1 1 .8 5; 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.