Dopamine Modulates Adaptive Forgetting in Medial Prefrontal Cortex

Abstract

Active forgetting occurs in many species, but how behavioral control mechanisms influence which memories are forgotten remains unknown. 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 relies on prefrontal control processes. Dopaminergic input to the prefrontal cortex is important for executive functions and cognitive flexibility. We found that, in a similar way, retrieval-induced forgetting of competing memories in male rats requires prefrontal dopamine signaling through D 1 receptors. Blockade of medial prefrontal cortex D 1 receptors as animals encountered a familiar object impaired active forgetting of competing object memories as measured on a later long-term memory test. Inactivation of the ventral tegmental area produced the same pattern of behavior, a pattern that could be reversed by concomitant activation of prefrontal D 1 receptors. We observed a bidirectional modulation of retrieval-induced forgetting by agonists and antagonists of D 1 receptors in the medial prefrontal cortex. These findings establish the essential role of prefrontal dopamine in the active forgetting of competing memories, contributing to the shaping of retention in response to the behavioral goals of an organism.

SKF82958, a dopamine D1 receptor agonist, disrupts prepulse inhibition in the medial prefrontal cortex and nucleus accumbens in C57BL/6J mice

“…It is currently unknown which brain regions are responsible for dopamine D1 receptors’ PPI-regulatory effects. Dopamine D1 receptors are expressed abundantly in brain regions such as the medial prefrontal cortex (mPFC)(Gallo et al ., 2022), nucleus accumbens (NAcc) (Zhao et al ., 2022), and ventral hippocampus (VH) (Papaleonidopoulos et al ., 2018), which are all associated with PPI regulation (Swerdlow et al , 2001). It is crucial to investigate whether dopamine D1 receptor activity in these regions affects PPI.…”