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. Author manuscript; available in PMC: 2021 Apr 16.
Published in final edited form as: Cell. 2020 Mar 17;181(2):410–423.e17. doi: 10.1016/j.cell.2020.02.055

Figure 7. The MEC-DG Pathway Mediates Memory Generalization and DG CCK+ Interneurons Mediate Memory Discrimination.

Figure 7.

(A) Schematics and representative images showing selective expression of hM4Di in MEC and LEC projection neurons, which send their axonal terminals to the DG MML or OML, respectively.

(B) Experimental scheme for inhibition of MEC or LEC during memory discrimination-generalization.

(C) Inhibiting the MEC enhanced discrimination between contexts A and B (Veh, n = 12; CNO, n = 10), but not A and C (n = 12, 9).

(D) Inhibiting the LEC did not affect generalization between contexts A and B (n = 12, 11) or A and C (n = 12, 10).

(E and F) Schematic (E) and representative image (F) for selective expression of NpHR in MEC projection neurons, which project to the MML of the DG.

(G) Experimental scheme to optogenetically inhibit the MEC-DG pathway during memory recall with 561 nm constant light.

(H) Inhibition of the MEC-DG pathway enhanced discrimination between contexts A and B (EYFP, n = 12; NpHR, n = 13), but not between contexts A and C (n = 10, 13).

(I) Genetic intersection strategy to target CCK+ GABAergic interneurons in DG.

(J) Representative images showing co-localization (white arrows) of labeled cells (mCherry+) with GAD67.

(K) Quantifications showing that labeled neurons were mostly GABAergic (GAD67+) and made up 28% of the GABAergic interneurons in the DG (n = 3).

(L) Experimental scheme to determine which interneuron subtypes are involved in memory discrimination-generalization.

(M) Inhibiting CCK+ interneurons in the DG reduced discrimination between contexts A and B (Veh, n = 17; CNO, n = 20), and between A and C (n = 17, 19).

(N and O) Discrimination was not affected by inhibiting PV+ interneurons (N, A and B: n = 16, 14; A and C: n = 13, 11) or SST+ interneurons (O, A and B: n = 14, 15; A and C: n = 13, 14).

Two-way mixed ANOVA with Sidak’s test was used for freezing levels, Mann-Whitney test for comparing discrimination indices, and one-sample t-test to compare discrimination indices with zero.