Despite the global medical community’s understanding of the significance of the prefrontal cortex in the consolidation of long-term memories, its role in the encoding of long-term memory remains elusive. Now, a study from researchers at The Scripps Research Institute identifies a sub-region in the prefrontal cortex that works to form a particular kind of memory, fear-associated with a specific environmental cue, otherwise known as contextual fear memory or conditioned fear. The team state that their study shows the medial prefrontal cortex is the site of this early protein synthesis, and that they have also identified which proteins are newly synthesized in the medial prefrontal cortex.
Previous studies show that the medial prefrontal cortex has many sub-regions, however, the specific roles of these sub-regions in encoding, expression and retrieval, as well as their underlying molecular mechanisms, remain to be unraveled. This is married with the fact that much is still unknown about the identities of proteins synthesized to produce long-term memory. The current study investigates the role of new protein synthesis in the mouse medial prefrontal cortex in encoding contextual fear memory.
The current study shows the new protein synthesis in a specific sub-region of the prefrontal cortex known in rodents as the prelimbic. The lab explain that, in humans, this area corresponds to the anterior cortex, which has been linked to processing emotional responses. They go on to add that when they closely examined effects on the brain of rodents conditioned with a mild foot shock, they found several messenger RNAs recruited to polyribosomes in the medial prefrontal cortex, a clear indication of new protein synthesis there.
The group also observed that when they inhibited new protein synthesis in the prelimbic region right after fear conditioning took place, those memories did not form. Results show that after just a few hours, inhibiting protein synthesis in prelimbic cortex had no impact and the memories took hold. Data findings show that this means there is temporal and spatial regulation of new protein synthesis in the medial prefrontal cortex. The researchers hypothesize it maybe that the first wave of protein synthesis is critical for encoding contextual fear memory, while the second wave in the other sub-regions is important for memory storage.
The team surmise that their study identifies several molecular substrates of new protein synthesis in the medial prefrontal cortex, and establishes that encoding of contextual fear memory requires new protein synthesis in the prelimbic subregion of medial prefrontal cortex. For the future, the researchers state that it remains to be determined if other sub-regions of the cortex are involved in the synthesis of memory proteins.