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. Author manuscript; available in PMC: 2020 Jun 3.
Published in final edited form as: Curr Biol. 2019 May 23;29(11):1885–1894.e4. doi: 10.1016/j.cub.2019.04.065

Figure 2. Acute activation of distinct memories drives discrete behavior across the longitudinal axis of the hippocampus.

Figure 2.

(A) A virus cocktail of AAV9-c-Fos-tTA and AAV9-TRE-eYFP was infused into the dorsal or ventral DG. (B) While on Dox, mice were fear conditioned in Context A. Dox was then removed prior to exposure to a novel Context B, and overlap of cells in the dDG or vDG was visualized. (C) Overlap between eYFP+ and c-Fos+ neurons was comparable between the dDG and vDG and, in both regions, significantly above chance (dashed line). Inset represents %positive cfos and % positive eYFP labeled cells. There were significantly more cFos+ and eYFP+ in the dDG than in the vDG. (D–E) Representative images (20X) of eYFP+ (green), c-Fos+ (red), and overlap of cells in the dDG or vDG. (F) A virus cocktail of AAV9-c-Fos-tTA and AAV9-TRE-ChR2-eYFP was infused into the dorsal or ventral DG. (G) While off Dox, mice were exposed to a female, neutral, or fear memory to label active cells with ChR2, returned to Dox, and administered light stimulation during re-exposure to the training context and an OPP/OPA paradigm. (H) Representative schematic of viral injection and optogenetic stimulation in the dorsal (top) and ventral (bottom) DG. (I, L) Activation of cells (Light On) processing a fear, but not a neutral or a female memory, in both the dorsal (I; female group: n=11; neutral group: n=12; fear group: n=12) and ventral (L; n=12/group) hippocampus drove freezing behavior in a neutral context relative to Light Off epochs. Repeated-measures ANOVA, significant Group × Epoch interaction, dorsal DG [F(2, 32)=41.23, p<0.01] and ventral DG [F(2, 33)=6.48, p<0.01]. (J, M) Light-activation of fear memories drove place avoidance while light-activation of female exposure memories drove place preference in both dorsal (one-way ANOVA, J, dDG [F(2,33)=53.44, p<0.01] and M, vDG [F(2,33)=34.75, p<0.01]). (K, N) In the absence of acute stimulation, fear, neutral, and female memories labeled a comparable amount of eYFP+ neurons in both the dDG (K) and vDG (N). White arrows indicate cells expressing eYFP and c-Fos.