Medial prefrontal cortex dopamine controls the persistent storage of aversive memories

Abstract

Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus.

Memory corticalization triggered by REM sleep: mechanisms of cellular and systems consolidation

“…3c) [171]. Importantly, inhibition of neuronal activity and protein synthesis in the mPFC 12 h after fear learning has been shown to impair remote LTM assessed 7 days, but not recent LTM tested 2 days after training [177]. Similar to results from dorsal CA1 in the HPC [178], this study reported that remote, but not recent LTM is modulated by D1/D5 dopaminergic receptors in the mPFC 12 h after training.…”

Dopamine D2 receptors gate generalization of conditioned threat responses through mTORC1 signaling in the extended amygdala

“…Because of the well-established role of DA in memory consolidation (17–21) we hypothesized that DA may control generalization by ensuring the precise consolidation of conditioned threat responses. Using a mouse behavioral paradigm for auditory threat response generalization, we observed that DA controls generalization through concomitant activation of D2 type receptors (D2R) in both the CEA and BNST.…”

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits

“…In support to this, intra-PFC infusion of dopamine D1, amino-hydroxymethyl-iso xazole propionate (AMPA) and glutamate N-methyl-Daspartate (NMDA) receptor antagonists or infusion of camino-butyrate type A (GABA A ) agonist were shown to interfere with aversive memory consolidation at distinct time windows. This effect was significant when applied at different time-points between 1.5 and 12 h after fear conditioning (Souza et al, 2000;Izquierdo et al, 2007;Gonzalez et al, 2014). In particular, blockade of D1 receptors in the medial PFC 6 h after training disrupts the long-term retrieval of a step-down inhibitory avoidance memory (Gonzalez et al, 2014).…”

“…This effect was significant when applied at different time-points between 1.5 and 12 h after fear conditioning (Souza et al, 2000;Izquierdo et al, 2007;Gonzalez et al, 2014). In particular, blockade of D1 receptors in the medial PFC 6 h after training disrupts the long-term retrieval of a step-down inhibitory avoidance memory (Gonzalez et al, 2014).…”

“…The encoding of emotional events is known to require the coordination of activity in limbic, thalamic and prefrontal cortical (PFC) circuits (Tayler and Wiltgen, 2013;Tovote et al, 2015). It has been demonstrated that the consolidation of some forms of memories can be modulated at distinct post-training time-windows (Dudai et al, 2015 instance, pharmacological manipulations of the PFC of rats at 3-6 h after conditioning are more effective in disrupting associative fear memory consolidation than treatments performed immediately after conditioning (Souza et al, 2000;Izquierdo et al, 2006Izquierdo et al, , 2007Gonzalez et al, 2014). A possible mechanism involves the synthesis of new proteins required for strengthening synaptic connections in fear-related circuits.…”