Optogenetic silencing of hippocampal inputs to the retrosplenial cortex causes a prolonged disruption of spatial working memory
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal
- Faculdade de Medicina Veterinária, Universidade Lusófona, Portugal
Figures
Figure 1 with 1 supplement
Viral vector expression and fiber-optic placement.
(A) Anatomical distribution of eYFP fluorescence expression in distinct AP coordinates of the retrosplenial cortex (RSC) after injection in the hippocampus (HIPP). (B) Injection spots in the HIPP. (C) Fiber-optic placement with two fiber-optic stubs at AP-reversed 30° angles reaching the two hemispheres at two distinct AP levels of RSC (arrows point to fiber-optic tracks, please see Figure 1—figure supplement 1 for low-magnification images of all animals and examples of high-magnification images).
Figure 1—figure supplement 1
Viral vector expression and fiber-optic placement on all animals.
Low-magnification anatomical distribution of eYFP fluorescence expression in the retrosplenial cortex (RSC) after injection in the hippocampus (HIPP) and position of the fiber-optic tracks (arrows), with high-magnification examples in the lower two panels, on all eArch (A) and CTRL (B) animals. (C) Example of a fiber-optic stub ‘full track’ placed at a 30° angle reaching the two hemispheres of RSC.
Figure 2
Delayed non-match to trajectory protocol and baseline performance.
(A) Delayed non-match to place (DNMP) protocol. Rats explore the unblocked arm in a sample run, then wait in the starting area for a 15 s delay. Once back on the track, with both arms unblocked, rats receive a reward if they choose the arm opposite the one explored in the sample run. (B) Training schedule, after reaching 75% performance, 3 baseline (no light delivered) sessions are followed by 10 sessions with illuminated trials interleaved with non-illuminated ones. (C) No differences in performance were observed in the baseline sessions (generalized linear mixed model [GLMM], p=0.212, Bonferroni post hoc test).
Figure 3
Optogenetic silencing of hippocampus (HIPP) terminals in retrosplenial cortex (RSC) causes a significant and prolonged decrease in performance.
(A) Illumination of RSC during delayed non-match to place (DNMP) leads to a significantly lower performance in eArch+, compared to empty-vector CTRL animals (CTRL: 0.81±0.03, ARCH: 0.73±0.08, generalized linear mixed model [GLMM], p=0.006, Bonferroni post hoc test). (B) In eArchT+ animals, we found no differences between performance in TI and NI trials taken as groups, both significantly lower than both baseline (p<0.001), and the corresponding trial groups in CTRL animals (TI, p=0.02, NI, p=0.008). In CTRL animals, no differences were found among the three groups (p=0.252 and 0.184). (C) Illumination on any given trial resulted in lower performance in the subsequent trial in eArch+, but not CTRL, animals (p=0.015), regardless of whether the illuminated trial is a correct or an incorrect trial. All summary data depicted is mean ± SD.
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Figure 3—source code 1
Performance in a given session, related to Figure 3.
- https://cdn.elifesciences.org/articles/96515/elife-96515-fig3-code1-v1.zip
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Figure 3—source code 2
Probability of correct trial given light delivered, related to Figures 3 and 4.
- https://cdn.elifesciences.org/articles/96515/elife-96515-fig3-code2-v1.zip
Figure 4
Optogenetic silencing of hippocampus (HIPP) terminals in retrosplenial cortex (RSC) causes persistent increase in errors.
(A) eArch+ animals exhibit persistent errors (p<0.001, Bonferroni post hoc test). (B) Persistent errors are absent in baseline (no light delivered) sessions (p=0.172, Bonferroni post hoc test). All summary data depicted is mean ± SD.
Figure 5
Behavioral impairments resulting from optogenetic silencing of hippocampus (HIPP) terminals in retrosplenial cortex (RSC) outlast illumination.
(A) eArch+ animals exhibit decreased performance once silencing occurred at T-1 (p=0.01, Bonferroni post hoc test), T-2 (p=0.033), T-3 (p=0.036), not T-4 (p=0.078). (B) Two consecutively non-illuminated trials after illumination still result in decreased performance on the subsequent trial (p=0.023, Mann-Whitney U). All summary data depicted is mean ± SD.
Figure 6
Animals spend more time at the choice point in correct trials unless hippocampus (HIPP) terminals in retrosplenial cortex (RSC) are silenced.
(A) CTRL animals spend more time at the choice point than eArch+ animals (p=0.02, fixed effect omnibus test). (B) This is true specifically for correct trials in both NI and TI (respectively, p=0.008 and p=0.045, simple effects parameter estimates). All summary data depicted is mean ± SD.
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Figure 6—source code 1
Time spent at the choice point, related to Figure 6.
- https://cdn.elifesciences.org/articles/96515/elife-96515-fig6-code1-v1.zip
Additional files
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Supplementary file 1
Generalized linear mixed model tables (A–H).
- https://cdn.elifesciences.org/articles/96515/elife-96515-supp1-v1.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/96515/elife-96515-mdarchecklist1-v1.docx
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Optogenetic silencing of hippocampal inputs to the retrosplenial cortex causes a prolonged disruption of spatial working memory
eLife 13:RP96515.
https://doi.org/10.7554/eLife.96515.3
