Transient acidosis while retrieving a fear-related memory enhances its lability
- Roy J and Lucille A Carver College of Medicine, University of Iowa, United States
- University of Toledo, United States
- Howard Hughes Medical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, United States
Figures
Figure 1 with 2 supplements
Inhaling CO2 during a retrieval tone augments the effect of extinction.
(A) Schematic of protocol for auditory aversive conditioning (also called fear conditioning), memory modification, and testing. The protocol contained four main components. (1) On day 1, mice …
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Figure 1—source data 1
Contexts for experiments.
Chart indicates the conditions used for contexts X, Y, Z, and ZZ.
- https://doi.org/10.7554/eLife.22564.003
Figure 1—figure supplement 1
Inhaling CO2 during a retrieval tone augments the effect of extinction.
In Figure 1, we assayed memory 5 days after extinction. Previous studies also tested memory 1 day after extinction. With that shorter interval, a retrieval cue did not produce a decrease in freezing …
Figure 1—figure supplement 2
The effect of CO2 on memory retrieval is concentration dependent.
We tested the effect of varying the CO2 concentration (5%, 10%, and 20%) and found that inhaling 10% CO2 during retrieval caused the greatest effect. Therefore, in subsequent experiments we used …
Figure 2 with 2 supplements
Inhaling CO2 during a retrieval tone augments the effect of reconditioning.
(A) Schematic of protocol for memory enhancement. During aversive conditioning, mice received 3 paired tones and foot shocks in context X. The Ret/CO2 period in context Y was as described for Figure …
Figure 2—figure supplement 1
Distinct contexts were used to test the effect of retrieval on memory enhancement.
(A) Schematic of protocol for auditory aversive conditioning, memory modification, and testing. The protocol was identical to that shown in Figure 2A. (B) Data are the percentage of time mice were …
Figure 2—figure supplement 2
Reconditioning enhances an aversive memory.
(A) Schematic of protocol for auditory aversive conditioning, memory modification, and testing. The protocol was identical to that shown in Figure 2A. (B–E) Data are percentage of time mice were …
Figure 3 with 2 supplements
CO2 inhalation enhances retrieval-dependent AMPAR current rectification.
(A) Schematic of experimental procedure. Aversive conditioning and Ret/CO2 were as described for Figure 1A. Ten minutes later, brain slices were prepared, and patch-clamp recordings were made from …
Figure 3—figure supplement 1
Inhaling CO2 does not alter synaptic strength in lateral amygdala neurons.
(A) Examples of miniature EPSCs. (B) Cumulative distributions of mEPSC amplitudes, inter-event intervals, and decay-times. n = 16–24 for each group. Data are mean±SEM. There were no statistically …
Figure 3—figure supplement 2
Prevention of shift from CI-AMPARs to CP-AMPARs weakens CO2 induced lability.
(A) Schematic of protocol for auditory aversive conditioning, memory modification, and testing. The behavioral protocol is the same as in Figure 1A. GluA23A or GluA23Y peptides were injected into …
Figure 4
Injecting acid into the amygdala before retrieval enhances exchange of AMPARs.
(A) Schematic of experimental procedure. Aversive conditioning was done as in Figure 1A. On day 2, mice received a microinjection of acidic saline (to reduce pH to ~6.8) or saline (pH ~7.35) into …
Figure 5
Inhaling CO2 does not enhance AMPAR exchange at synapses between the cortex and lateral amygdala.
The procedure was the same as that shown in Figure 3A except that stimulation was of cortical inputs. (A,B) Left, AMPAR current-voltage relationships in lateral amygdala pyramidal neurons. Insets …
Figure 6
CO2-induced acidosis increases stimulation-dependent postsynaptic [Ca2+]i in amygdala slices and increases CREB phosphorylation after retrieval.
(A) Schematic for measuring changes in post-synaptic [Ca2+]i. Brain slices were prepared, and lateral amygdala pyramidal neurons were loaded with the fluorescent Ca2+ indicator Oregon Green 488 …
Figure 7 with 1 supplement
CO2 inhalation enhances retrieval-induced activation of lateral amygdala neurons bearing an aversive memory trace.
(A) Schematic showing procedure; see also Figure 7—figure supplement 1 for additional information about the doxycycline-inducible system. The activity-dependent promoter Fos was used to induce …
Figure 7—figure supplement 1
Schematic showing how neurons were labeled in mice transgenic for TetTag Fos-tTA and microinjected with the viral vector AAV9-TRE-mCherry.
Neuronal activity activates the Fos promoter. The Fos promoter drives expression of the tetracycline transactivator (tTA) and of shEGFP. The shEGFP protein is rapidly degraded with a 2 hr half-life. …
