Functional characterization of des-IGF-1 action at excitatory synapses in the CA1 region of rat hippocampus

J Neurophysiol. 2005 Jul;94(1):247-54. doi: 10.1152/jn.00768.2004.


Insulin-like growth factor-1 (IGF-1) and growth hormone play a major role in the growth and development of tissues throughout the mammalian body. Plasma IGF-1 concentrations peak during puberty and decline with age. We have determined that chronic treatments to restore plasma IGF-1 concentrations to adult levels attenuate spatial learning deficits in aged rats, but little is known of the acute actions of IGF-1 in the brain. To this end, we utilized hippocampal slices from young Sprague-Dawley rats to characterize the acute effects of des-IGF-1 on excitatory synaptic transmission in the CA1 region. We observed a 40% increase in field excitatory postsynaptic potential (fEPSP) slope with application of des-IGF-1 (40 ng/ml) and used whole cell patch-clamp recordings to determine that this enhancement was due to a postsynaptic mechanism involving alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) but not N-methyl-D-aspartate receptors. Furthermore, the enhancement was completely blocked by the broad-spectrum tyrosine kinase inhibitor, genistein (220 microM), and significantly reduced by the PI3K blockers wortmannin (1 microM) and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (10 microM), suggesting that the effect was predominantly dependent on PI3K activation. This characterization of the acute actions of des-IGF-1 at hippocampal excitatory synapses may provide insight into the mechanism by which long-term increases in plasma IGF-1 impart cognitive benefits in aged rats. Increases in AMPA receptor-mediated synaptic transmission may contribute directly to cognitive improvement or initiate long-term changes in synthesis of proteins such as brain-derived neurotrophic factor that are important to learning and memory.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Animals, Newborn
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Genistein / pharmacology
  • Hippocampus / cytology*
  • Hippocampus / physiology
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques / methods
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / drug effects*
  • Synaptic Transmission / drug effects*
  • Wortmannin
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Androstadienes
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Insulin-Like Growth Factor I
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Genistein
  • Wortmannin