Fear memory formation can affect a different memory: fear conditioning affects the extinction, but not retrieval, of conditioned taste aversion (CTA) memory

Abstract

The formation of fear memory to a specific stimulus leads to subsequent fearful response to that stimulus. However, it is not apparent whether the formation of fear memory can affect other memories. We study whether specific fearful experience leading to fear memory affects different memories formation and extinction. We revealed that cued fear conditioning, but not unpaired or naïve training, inhibited the extinction of conditioned taste aversion (CTA) memory that was formed after fear conditioning training in rats. Fear conditioning had no effect on retrieval of CTA memory but specifically impaired its extinction. Extinguished fear memory, after fear extinction training, had no effect on future CTA memory extinction. Fear conditioning had no effect on CTA memory extinction if CTA memory was formed before fear conditioning. Conditioned taste aversion had no effect on fear conditioning memory extinction. We conclude that active cued fear conditioning memory can affect specifically the extinction, but not the formation, of future different memory.

Keywords: conditioned taste aversion; cued fear conditioning; learning and memory; memory extinction; memory retrieval.

Figure 1

Fear conditioning affects conditioned taste aversion memory (CTA) extinction. (A) Experimental timeline: animals were trained for fear conditioning (n = 15), unpaired (n = 13) or left naïve (n = 20). The next day they were tested for fear memory to the tone. Four days later the animals were subjected to CTA training. Three days later they were tested for taste memory once each day for 6 days. (B) Freezing during fear memory test is significantly higher in fear conditioned animals compared to unpaired trained animals (χ²₍₁₎ = 87.779; p < 0.003). This result shows that fear memory to the tone was formed in the fear conditioned but not unpaired trained rats. (C) Conditioned taste aversion memory extinction is significantly slower in animals that were trained previously for fear conditioning compared to animals trained with unpaired protocol or left naïve. The analysis revealed a significant main effect for groups (χ²₍₂₎ = 10.162; p < 0.007). There is interaction between groups and time variables (χ²₍₂₎ = 12.712; p < 0.003). Analysis between groups revealed that there is an interaction between the fear conditioning and naïve groups (χ²₍₁₎ = 7.583, p < 0.007), between the fear conditioning and unpaired groups (χ²₍₁₎ = 6.295, p < 0.02) but not between the unpaired and naïve groups (χ²₍₁₎ = 0.013, p > 0.9). (D) Conditioned taste aversion memory retrieval is not affected by fear conditioning. Animals were trained for fear conditioning or left naïve. Four days later animals were trained for CTA using lower concentration of LiCl (3 ml of 0.015 M LiCl) to study whether fear conditioning can enhance CTA memory retrieval. Conditioned taste aversion memory was not significantly different between fear-conditioned or naïve trained animals (p > 0.3) showing that CTA memory retrieval is not affected by fear conditioning.

Figure 2

Extinguished fear conditioning memory has no effect on CTA memory extinction. (A) Experimental timeline: animals were trained for fear conditioning or left naïve (n = 10). The next day the fear conditioned trained animals were divided into two groups: the first was tested for fear memory to the tone (two tones (n = 8)) and the second subjected to the fear conditioning extinction protocol (n = 12). Four days later the animals were subjected to CTA training. Three days later they were tested for taste memory once each day for 6 days. (B) Freezing during fear memory test and during fear memory extinction protocol. Freezing was not different between groups on the second tone (p > 0.5) but was significantly and markedly reduced in the extinction group on the 19th tone when compared to the second tone between groups (p < 0.003) or within the extinction group (p < 0.001). (C) Conditioned taste aversion memory extinction is significantly slower in animals that were trained previously for fear conditioning compared with animals trained with fear memory extinction protocol or left naïve. The analysis revealed significant main effect for group (χ²₍₂₎ = 14.886; p < 0.002). There is an interaction between groups and time variables ((χ²₍₂₎ = 19.915; p < 0.001). Analysis between groups revealed that there is an interaction between fear conditioning and naïve groups (χ²₍₁₎ = 5.630, p < 0.02), between fear conditioning and extinction groups (χ²₍₁₎ = 16.054, p < 0.001) but not between extinction and naïve groups (χ²₍₁₎ = 1.256, p > 0.2).

Figure 3

Fear conditioning has no effect on CTA memory extinction if CTA memory was formed before fear conditioning learning. (A) Experimental time line. Rats were trained for CTA memory. Three days later they were divided into two groups that were trained with fear conditioning (n = 5) or left without training (naïve, n = 8). The next day the animals were tested for fear memory formation. Twenty four hours later the animals were tested for CTA memory extinction. (B) No difference in CTA memory extinction was detected between the naïve and fear conditioning trained rats (χ²₍₁₎ = 0.02, p > 0.9).

Figure 4

Conditioned taste aversion training has no effect on fear memory extinction. (A) Experimental timeline: animals were paired with saccharin and LiCl (CTA; n = 11) or saccharin and saline (control; n = 10). Three days later they were tested for taste aversion memory. The next day they were trained for fear conditioning. The following next 2 days the animals were subjected to the fear memory extinction protocol. (B) Taste aversion is significantly higher in the CTA group compared to the control (p < 0.001) showing that the CTA trained animals formed taste aversion memory. (C) Fear memory extinction is not different between animals subjected to CTA or controls in both test days. In the first test day there is no main effect for group (CTA, saline controls) (χ²₍₁₎ = 2.037, p > 0.15) and no interaction between group and time variables (χ²₍₁₎ = 0.062, p > 0.8). In the second test day there is no main effect for group (CTA, saline controls) (χ²₍₁₎ = 0.091, p > 0.7) and no interaction between group and time variables (χ²₍₁₎ = 0.101, p > 0.7).