title: Permissive role of insulin in the expression of long-term potentiation in the hippocampus of immature rats.
abstract: Many studies indicate that impairment in insulin signaling leads to learning and memory deficits. However, previous studies failed to establish a clear role of insulin in long-term potentiation (LTP), the best cellular model of memory formation. Here we show that while insulin pretreatment did not affect LTP magnitude in the adult rat hippocampus, it facilitated LTP expression in the immature hippocampus. The tyrosine kinase inhibitor AG-1024 abolished the effect of insulin in young rats, suggesting the involvement of the insulin receptor. On the other hand, increasing extracellular glucose concentration failed to facilitate LTP and application of an insulin-responsive glucose transporter-4 inhibitor did not impair the effect of insulin. These results suggest that the facilitatory action of insulin on LTP is not an indirect effect on glucose homeostasis/utilization. Involvement of the MAPK/ERK pathway, a known downstream pathway of insulin signaling, was revealed by pretreatment with PD98059, which blocked the insulin-mediated LTP facilitation. Consistent with this, high-frequency stimulation induced a significant increase in the level of phosphorylated Erk-2 in insulin-treated hippocampus. Taken together, these results suggest that insulin may be an essential factor in the immature brain, allowing the expression of LTP to facilitate learning and memory.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Zhao
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000502:physiology
chemical_list: D007328:Insulin; D011972:Receptor, Insulin