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.
Highlights
Medial prefrontal cortex plays a critical role in remote memory retrieval as well as in the consolidation and recall of recent memories (Runyan et al, 2004; Frankland and Bontempi, 2005; Gonzalez et al, 2013). mPFC dopamine (DA) signaling has been involved in cognitive, emotional and motivational processes (Seamans et al, 1998; Pezze et al, 2003; Laviolette et al, 2005; Lauzon et al, 2009)
Given that ventral tegmental area (VTA) dopamine neurons signal aversion, saliency and novelty (Lammel et al, 2008, 2011; BrombergMartin et al, 2010) and a subset of VTA DA neurons projecting to mPFC are activated by aversive stimuli (Abercrombie et al, 1989; Bassareo et al, 2002; Brischoux et al, 2009; Lammel et al, 2011, 2012), we investigated whether D1/D5 DA receptors in mPFC are involved in inhibitory avoidance task (IA) long-term memory (LTM) processing
More recent findings suggest that learning reactive fear responses engages different brain circuitry than learning active fear responses (Yang and Liang, 2014), suggesting that memory processing could differ between tasks
Summary
Medial prefrontal cortex (mPFC) plays a critical role in remote memory retrieval as well as in the consolidation and recall of recent memories (Runyan et al, 2004; Frankland and Bontempi, 2005; Gonzalez et al, 2013). mPFC dopamine (DA) signaling has been involved in cognitive, emotional and motivational processes (Seamans et al, 1998; Pezze et al, 2003; Laviolette et al, 2005; Lauzon et al, 2009). The ventral tegmental area (VTA) is the primary source of DA afferents to the mPFC (Lammel et al, 2012) These projections are activated by aversive stimuli (Lammel et al, 2012) and it has been shown that different kinds of aversive experiences increase DA levels within this cortex (Abercrombie et al, 1989; Horvitz, 2000; Bassareo et al, 2002), suggesting that DA signaling in mPFC may play a critical role in the lasting storage of memories for fearful or noxious stimuli. We showed that maintenance of fear memory is modulated by the VTA through the late posttraining activation of DA D1/D5 receptors in the dorsal hippocampus (Rossato et al, 2009). We found that activation of D1/D5 receptors in mPFC immediately and late after learning is critical for maintenance of the long-term memory (LTM) trace induced by both hippocampus-dependent and hippocampus-independent aversion-motivated learning tasks, indicating that mPFC regulates memory durability regardless of the aversive properties of the stored information
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