Role of Rac1 and Medial Temporal Lobe Structures in Retrieval-Induced Forgetting

Retrieval-induced forgetting (RIF) is a form of adaptive forgetting in which selective retrieval of a memory leads to the forgetting of related, competing memories. Our laboratory developed a rodent model of RIF based on object recognition that reproduces key features of the phenomenon observed in humans. Previous work showed that RIF depends on medial prefrontal cortex (mPFC) activity and dopamine D1 receptor activation in this region, and that hippocampal (HP) activity decreases during retrieval practice. However, whether HP and perirhinal cortex (PrC) are causally involved in RIF, and the molecular mechanisms sustaining this form of forgetting over time, remain unknown. This project investigates neuronal activity in the mPFC, HP, and PrC during selective retrieval, and evaluates whether Rac1, a protein involved in synaptic plasticity and memory persistence, mediates RIF by locally inhibiting its activity in HP and PrC during and after retrieval practice. Preliminary results show that local infusion of the Rac1 inhibitor 1A-116 into dorsal CA1 promoted the persistence of object recognition memory for at least 72 hours, suggesting that Rac1 blockade through this route may be a suitable approach to study RIF.