166 | Serotonin 2A receptor activity in the rat mPFC promotes Retrieval-Induced Forgetting in rats by modulating dCA1

Cognition, Behavior, and Memory

Author: María Belén Zanoni Saad | Email: mbzanoni@gmail.com

María Belén Zanoni Saad , Mariana Imperatori , Pedro Bekinschtein , Noelia Weisstaub

1° Laboratorio de Memoria y Cognición Molecular, Instituto de Neurociencia Cognitiva y Traslacional, CONICET-Fundación INECO-Universidad Favaloro, Buenos Aires, Argentina

Forgetting is a ubiquitous phenomenon that is actively promoted in many species. The act of remembering some experiences can cause forgetting of others, in both humans and rats. We previously found that when rats need to retrieve a memory to guide exploration, it reduces later retention of other competing memories encoded in that environment. As with humans, this retrieval-induced forgetting (RIF) relies on prefrontal control processes, is competition-dependent, and is cue-independent. RIF is thought to be driven by inhibitory control signals from the prefrontal cortex that target areas where the memories are stored. This work aims to explore if and how the serotonergic system participates in RIF and, in particular, if the ?arr2 signaling pathway is recruited when competition between memories is taking place. Additionally, we studied if the mPFC-Nucleus Reuniens (RE) – Dorsal CA1 (dCA1) circuit is supporting this phenomenon.
We modified the spontaneous object recognition procedure and used a pharmacological approach to manipulate the serotonin receptor 2A (5-HT2AR) activity and signaling in the medial Prefrontal Cortex (mPFC) of rats and also to inhibit downstream structures.
We found that RIF in rats requires prefrontal serotonin signaling through 5-HT2AR and the ?arr2 signaling pathway is at least one of the pathways recruited. Importantly, RIF depends not only on the activity of dCA1 and RE separately but also on the signaling between the mPFC 5-HT2AR and the dCA1.