Extracellular Signal-Regulated Kinase Activity in the Entorhinal Cortex Is Necessary for Long-Term Spatial Memory

Abstract

Lesion studies have provided evidence that the entorhinal cortex (EC) participates in spatial memory. However, the molecular cascades that underlie memory-associated changes in the EC and its specific role in spatial memory, however, have not been clearly delineated. Recently, it has been shown that activation of extracellular signal-regulated kinase (Erk, a mitogen-activated protein kinase family member) in the dorsal hippocampus is necessary for spatial memory. To examine whether similar mechanisms are used for spatial memory storage in the EC, Erk activity was inhibited after training in the Morris water maze. Bilateral infusion of the mitogen-activated protein kinase kinase inhibitor PD098059 into the EC immediately after training resulted in a memory deficit observed during a retention test performed 48 h later. This deficit was abolished with pretraining in a different water maze in which animals were able to learn the general task requirements and the appropriate search strategies. The absence of a deficit indicates that Erk activity in the EC may be involved in storing the task requirements or the search strategies. The findings presented in this article are consistent with the idea that the EC is involved in spatial memory and indicate that Erk activity is necessary for memory consolidation in this structure.

A Role for Prefrontal Cortex in Memory Storage for Trace Fear Conditioning

“…In previous reports, long-term memory storage has been correlated to the activation of Erk within specific brain structures (Berman et al, 1998;Blum et al, 1999;Schafe et al, 2000;Hebert and Dash, 2002). This is consistent with our results indicating a requirement for Erk activation in the hippocampus for long-term memory of trace fear conditioning.…”

“…In mammals the activation and necessity of Erk within structures including the insular cortex (Berman et al, 1998), the hippocampus (Blum et al, 1999), the entorhinal cortex (Hebert and Dash, 2002), and the amygdala (Schafe et al, 2000) have been demonstrated to be required in various memory tasks. Unlike lesion studies, inhibition of Erk allows for the assessment of long-term memory storage within a structure without causing a generalized dysfunction evidenced by intact acquisition (Blum et al, 1999) and short-term memory (Martin et al, 1997;Schafe et al, 2000).…”

Amnesia or retrieval deficit? Implications of a molecular approach to the question of reconsolidation

“…ERK has been implicated in both synaptic plasticity (English and Sweatt 1996;Martin et al 1997) and the consolidation of numerous learning paradigms (Atkins et al 1998;Berman et al 1998;Blum et al 1999;Hebert and Dash 2002;Kelly et al 2003). More recently, studies have established that activation of ERK is not only necessary for memory consolidation, but reconsolidation as well.…”

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

“…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 , 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.…”