Serotonin Type 2a Receptor in the Prefrontal Cortex Controls Perirhinal Cortex Excitability During Object Recognition Memory Recall.

Previous experiences can drive adaptive behavior based on different characteristics, including contextual ones. Indeed, contextual information can be used as a criterion to guide the recall of the most relevant memory trace and the inhibition of others. The medial Prefontal Cortex (mPFC) has been proposed as an area that plays a pivotal role in regulating the retrieval of memory traces in downstream regions. Also, we have shown that mPFC Serotonin 2a Receptors (5-HT2aR) modulates the retrieval of a contextually guided recognition memory task and modulates the retrieval and reconsolidation of memories in the Perirhinal Cortex (PRH). However, how the mPFC output mediated by the 5-HT2aR activity is modulating memory retrieval in the PRH is a question that remains unclear. To tackle this question, we analyzed neuronal activity in the PRH and mPFC, by measuring expression of the immediate early gene c-Fos. We combined behavioral, pharmacological and immunohistochemical techniques to examine how mPFC 5-HT2aR controls mPFC and the PRH activity. We found that blockade of mPFC 5-HT2aR increase the level of c-Fos expression in the PHR and that this increase correlates with animals' performance in the task. We also found an increase in c-Fos expression in the mPFC after mPFC 5-HT2aR blockade that does not correlate with the animals' behavioral response. However, these changes showed a significant correlation with those observed in the PRH. These results suggest that mPFC 5-HT2aR signaling may modulate the behavioral response during memory recall by controlling the neuronal activation in the PRH.