Sex and the facilitation of cued fear by prior contextual fear conditioning in rats.

Previous studies have shown that the formation of new memories can be influenced by prior experience. This includes work using pavlovian fear conditioning in rodents that have shown that an initial fear conditioning experience can become associated with and facilitate the acquisition of new fear memories, especially when they occur close together in time. However, most of the prior studies used only males as subjects resulting in questions about the generalizability of the findings from this work. Here we tested whether prior contextual fear conditioning would facilitate later learning of cued fear conditioning in both male and female rats, and if there were differences based on the interval between the two conditioning episodes. Our results showed that levels of cued fear were not influenced by prior contextual fear conditioning or by the interval between training, however, females showed lower levels of cued fear. Freezing behavior in the initial training context differed by sex, with females showing lower levels of contextual fear, and by the type of initial training, with rats given delayed shock showing higher levels of fear than rats given immediate shock during contextual fear conditioning. These results indicate that contextual fear conditioning does not prime subsequent cued fear conditioning and that female rats express lower levels of cued and contextual fear conditioning than males.

Sex difference in the facilitation of fear learning by prior fear conditioning.

There is now ample evidence that the strength and underlying mechanisms of memory formation can be drastically altered by prior experience. However, the prior work using rodent models on this topic has used only males as subjects, and as a result, we do know whether or not the effects of prior experience on subsequent learning are similar in both sexes. As a first step towards addressing this shortcoming, rats of both sexes were given auditory fear conditioning, or fear conditioning with unsignaled shocks, followed an hour or a day later by a single pairing of light and shock. Fear memory for each experience was assessed by measuring freezing behavior to the auditory cue and fear-potentiated startle to the light. Results showed that males trained with auditory fear conditioning showed facilitated learning to the subsequent visual fear conditioning session when the two training sessions were separated by one hour or one day. Females showed evidence of facilitation in rats given auditory conditioning when they were spaced by an hour but not when they were spaced by one day. Contextual fear conditioning did not support the facilitation of subsequent learning under any conditions. These results indicate that the mechanism by which prior fear conditioning facilitates subsequent learning differs between sexes, and they set the stage for mechanistic studies to understand the neurobiological basis of this sex difference.

Sex difference in the facilitation of fear learning by prior fear conditioning.

There is now ample evidence that the strength and underlying mechanisms of memory formation can be drastically altered by prior experience. However, the prior work using rodent models on this topic has used only males as subjects, and as a result, we do know whether or not the effects of prior experience on subsequent learning are similar in both sexes. As a first step towards addressing this shortcoming rats of both sexes were given auditory fear conditioning, or fear conditioning with unsignaled shocks, followed an hour or a day later by a single pairing of light and shock. Fear memory for each experience was assessed by measuring freezing behavior to the auditory cue and fear-potentiated startle to the light. Results showed that males trained with auditory fear conditioning showed facilitated learning to the subsequent visual fear conditioning session when the two training sessions were separated by one hour or one day. Females showed evidence of facilitation in rats given auditory conditioning when they were spaced by an hour, but not when they were spaced by one day. Contextual fear conditioning did not support the facilitation of subsequent learning under any conditions. These results indicate that the mechanism by which prior fear conditioning facilitates subsequent learning differs between sexes, and they set the stage for mechanistic studies to understand the neurobiological basis of this sex difference.

Subthreshold Fear Conditioning Produces a Rapidly Developing Neural Mechanism that Primes Subsequent Learning.

Learning results in various forms of neuronal plasticity that provide a lasting representation of past events, and understanding the mechanisms supporting lasting memories has been a primary pursuit of the neurobiological study of memory. However, learning also alters the capacity for future learning, an observation that likely reflects its adaptive significance. In the laboratory, we can study this essential property of memory by assessing how prior experience alters the capacity for subsequent learning. Previous studies have indicated that while a single weak fear conditioning trial is insufficient to support long-term memory (LTM), it can facilitate future learning such that another trial delivered within a protracted time window results in a robust memory. Here, we sought to determine whether or not manipulating neural activity in the basolateral amygdala (BLA) using designer receptors exclusively activated by designer drugs (DREADDs) during or after the initial learning trial would affect the ability of the initial trial to facilitate subsequent learning. Our results show that inhibiting the BLA in rats prior to the first trial prevented the ability of that trial to facilitate learning when a second trial was presented the next day. Inhibition of the BLA immediately after the first trial using DREADDs was not effective, nor was pharmacological inhibition of protein kinase A (PKA) or the mitogen-activated protein kinase (MAPK). These findings indicate that the neural mechanisms that permit an initial subthreshold fear conditioning trial to alter later learning develop rapidly and do not appear to require a typical post-learning consolidation period.