The Role of Insulin Receptor Signaling in Synaptic Plasticity and Cognitive Function

Insulin is the most abundant peptidergic hormone secretedby the pancreatic islets of Langerhans and plays an importantrole in organic metabolism. In recent years, various functionsfor insulin receptor signaling in the brain have been suggestedin normal neurophysiology, and a dysregulation of insulinsecretion or insulin receptor signaling has been reported inserious mental illnesses. Several lines of work in both laboratoryanimals and humans suggest that when neurons in cognitivebrain regions such as the hippocampus and cerebral cortexdo not make enough insulin or cannot respond to insulin properly,everything from very mild memory loss to severeneorodegenerative diseases can result. On the other hand,administration of insulin exerts memory-enhancing action inboth humans and experimental animals. Insulin has alsorecently been shown to regulate the endocytosis of 3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, which causes long-term depression(LTD) of excitatory synaptic transmission. The fact that LTD in the mammalian brain is generallyassumed to be a synaptic mechanism underlying learning during novel experiences,this insulin-induced LTD may therefore serve as an important role in brain informationprocessesing. Recent advances in the knowledge of the biological role of brain insulin receptorsignaling in relation to synaptic plasticity and cognitive function, and of the regulatorysignaling mechanisms involved in these processes will be discussed in the article.