Differential involvement of dopamine D1 receptor and MEK signaling pathway in the ventromedial prefrontal cortex in consolidation and reconsolidation of recognition memory

Abstract

We investigated MEK and D1 receptors in the ventromedial prefrontal cortex (vmPFC) in consolidation and reconsolidation of recognition memory in rats nonhabituated to the experimental context (NH) or with reduced arousal due to extensive prior habituation (H). The D1 receptor antagonist enhanced consolidation and impaired reconsolidation in NH but impaired consolidation with no effect on reconsolidation in H. The D1 receptor agonist had no effect on consolidation in either H or NH but impaired reconsolidation in both groups. The MEK inhibitor impaired consolidation and reconsolidation, regardless of arousal. Thus, vmPFC D1 receptors and MEK show differential involvement in memory and arousal.Evidence indicates that the prefrontal cortex (PFC) plays an important role in long-term recognition memory processes (Meunier et al. 1997;Ragozzino et al. 2002). Indeed, we have recently shown that both protein synthesis and NMDA receptors are required for consolidation and reconsolidation of recognition memory in the ventromedial PFC (vmPFC) (Akirav and Maroun 2006). Dopamine D1 receptors play an important role in prefrontal function, such as working memory, and there is evidence that dopamine D1 receptor activity can modulate plasticity (Gurden et al. 2000;Chen et al. 2007;Nagai et al. 2007;Rinaldi et al. 2007;Vijayraghavan et al. 2007). It has been suggested that the dopamine D1 receptor extracellular signal-regulated kinase (ERK1/2) signaling pathway in the PFC is critically involved in molecular adaptations that are necessary for long-term behavioral and neuronal plasticity (Nagai et al. 2007). The phosphorylation of ERK has been shown to be a correlate for plasticity (for review, see Sweatt 2004) and long-term memory for taste (Berman et al. 1998), fear conditioning (Schafe et al. 2000, and spatial tasks (Blum et al. 1999;Hebert and Dash 2002). Nagai et al. (2007) have found that dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via ERK in the PFC.Exposure to stress is known to precipitate many neuropsychiatric disorders such as depression and schizophrenia (Mazure 1995). These disorders involve memory deficits caused by PFC dysfunction (Mattes 1980;Weinberger et al. 1986;Deutch 1993;Fibiger 1995). Experimental evidence has shown that acute mild stressful stimuli such as exposure to novelty increases dopamine (DA) and dopamine metabolism in the PFC, producing working memory impairment that can be blocked by agents that prevent the increase in DA turnover (Murphy et al. 1996;Enrico et al. 1998;Takahata and Moghaddam 1998;Ihalainen et al. 1999;Feenstra et al. 2000;Del Arco and Mora 2001).We have recently shown that novelty or familiarity with the experimental arena, which differentially affects the arousal level of the rat, also has a differential effect on consolidation and reconsolidation of object recognition memory. Specifically, learning was tested under two arousal conditions: no previous habituation to the experimental context (high novelty stress/arousal level) or extensive...

Differential Involvement of Brain-Derived Neurotrophic Factor in Reconsolidation and Consolidation of Conditioned Taste Aversion Memory

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Enhanced noradrenergic activity potentiates fear memory consolidation and reconsolidation by differentially recruiting α1- and β-adrenergic receptors

“…Of note, an unequal recruitment of these brain regions, which are heterogeneously exposed to noradrenaline (van Veldhuizen et al 1994), has been documented during consolidation and reconsolidation of the same type of memory (Taubenfeld et al 2001;Garcia-Delatorre et al 2010). For instance, the prefrontal cortex can be differentially recruited during these memory phases depending on the arousal level induced by the task to be performed (Maroun and Akirav 2009). Of potential relevance to the present set of results is the higher expression of a1-adrenergic receptors in the latter area relative to that found in hippocampus and amygdala (Rainbow and Biegon 1983;Nicholas et al 1996).…”

Consolidation and Reconsolidation: Two Lives of Memories?

“…von Hertzen et al, 2005; Maroun & Akirav 2009; Taubenfeld et al, 2001; Lee et al, 2004, 2008a, 2010; reviewed in Alberini 2005). Furthermore, several reconsolidation studies have shown that as time passes memories become resistant to reconsolidation blockers (Milekic et al, 2002; Suzuki et al, 2004; Eisenberg et al, 2004), though others have found conflicting results (Debiec et al, 2002; Wang et al, 2009; Robinson et al, 2010).…”