title: Hippocampal extracellular signal-regulated kinase signaling has a role in passive avoidance memory retrieval induced by GABAA Receptor modulation in mice.
abstract: Available evidence strongly suggests that the γ-aminobutyric acid type A (GABA(A)) receptor has a crucial role in memory retrieval. However, the signaling mechanisms underlying the role of GABA(A) 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 GABA(A) receptor modulation on memory retrieval. We further tested the co-involvement of signaling molecules: extracellular signal-regulated kinase (ERK), Ca(2+)/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 GABA(A) receptor activation or inhibition induces ERK phosphorylation during memory retrieval, drugs that target the GABA(A) receptor were administered into the hippocampus before the retention trial. Muscimol, a GABA(A) receptor agonist, and diazepam, an agonist to benzodiazepine-binding site of GABA(A) 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 GABA(A) 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 GABA(A) receptor-mediated memory retrieval is closely related to ERK activity.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Seungheon
authors.initials: S
authors.lastname: Lee
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases; D018682:GABA Agents / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections / Q000379:methods; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011963:Receptors, GABA-A; D012153:Retention, Psychology / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D018682:GABA Agents; D011963:Receptors, GABA-A; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases