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Hippocampal Extracellular Signal-Regulated Kinase Signaling has a Role in Passive Avoidance Memory Retrieval Induced by GABAA Receptor Modulation in Mice

2011; Springer Nature; Volume: 37; Issue: 5 Linguagem: Inglês

10.1038/npp.2011.311

1740-634X

Dong Hyun Kim, Jong‐Min Kim, Se Jin Park, Seungheon Lee, Chan Young Shin, Jae Hoon Cheong, Jong Hoon Ryu,

Neuroinflammation and Neurodegeneration Mechanisms

Available evidence strongly suggests that the γ-aminobutyric acid type A (GABAA) receptor has a crucial role in memory retrieval. However, the signaling mechanisms underlying the role of GABAA receptor modulation in memory retrieval are unclear. We conducted one-trial passive avoidance task with pre-retention trial drug administration in the hippocampus to test the effects of GABAA receptor modulation on memory retrieval. We further tested the co-involvement of signaling molecules: extracellular signal-regulated kinase (ERK), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and cAMP responsive element-binding protein (CREB). First, we observed that the phosphorylation of hippocampal ERK was required for memory retrieval during the task. Accordingly, to investigate whether GABAA receptor activation or inhibition induces ERK phosphorylation during memory retrieval, drugs that target the GABAA receptor were administered into the hippocampus before the retention trial. Muscimol, a GABAA receptor agonist, and diazepam, an agonist to benzodiazepine-binding site of GABAA receptor, blocked retention trial-induced ERK phosphorylation and impaired memory retrieval. Furthermore, co-treatment with sub-effective dose of U0126, a mitogen-activated protein kinase inhibitor, blocked the upregulation of ERK phosphorylation and impaired memory retrieval, and bicuculline methiodide (BMI), a GABAA receptor antagonist, increased ERK phosphorylation induced by the retention trial and facilitated memory retrieval. Finally, the effects of BMI were blocked by the co-application of a sub-effective dose of U0126. These results suggest that GABAA receptor-mediated memory retrieval is closely related to ERK activity.