TY - JOUR T1 - Subthreshold fear conditioning produces a rapidly developing neural mechanism that primes subsequent learning JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0113-19.2019 SP - ENEURO.0113-19.2019 AU - Kehinde E. Cole AU - Jessica Lee AU - Michael Davis AU - Ryan G. Parsons Y1 - 2019/06/20 UR - http://www.eneuro.org/content/early/2019/06/20/ENEURO.0113-19.2019.abstract N2 - 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, 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 or the mitogen activated protein kinase. 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.Significance Statement Laboratory studies of memory are typically designed to identify mechanisms that allow the brain to represent past experience. The purpose of this ability is likely so that prior learning can direct future behavior, however studies are most often focused on the storage aspects of memory and less on how later experience is altered. We used a fear conditioning paradigm in which a single trial, subthreshold for producing long-term behavioral change, primes future learning when a second trial is later encountered. Neural activity in the amygdala was required for long-term memory priming, however post-training disruption of neural activity or cell signaling events had no effect. These results provide insight into the mechanisms that allow prior aversive experience to modify new learning. ER -