Blocking the NGF-TrkA interaction rescues the developmental loss of LTP in the rat visual cortex: role of the cholinergic system

Neuron. 2000 Jan;25(1):165-75. doi: 10.1016/s0896-6273(00)80880-6.

Abstract

Although nerve growth factor (NGF) is a crucial factor in the activity-dependent development and plasticity of visual cortex, its role in synaptic efficacy changes is largely undefined. We demonstrate that the maintenance phase of long-term potentiation (LTP) is blocked by local application of exogenous NGF in rat visual cortex at an early stage of postnatal development. Long-term depression (LTD) and bidirectional plasticity are unaffected. At later postnatal ages, blockade of either endogenous NGF by immunoadhesin (TrkA-IgG) or TrkA receptors by monoclonal antibody rescues LTP. Muscarinic receptor activation/inhibition suggests that LTP dependence on NGF is mediated by the cholinergic system. These results indicate that NGF regulates synaptic strength in well-characterized cortical circuitries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibody Specificity
  • Atropine / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Immunoglobulin G / pharmacology
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Lysine / analogs & derivatives
  • Lysine / pharmacokinetics
  • Muscarinic Antagonists / pharmacology
  • Nerve Growth Factor / immunology
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / chemistry
  • Neurons / cytology
  • Neurons / metabolism
  • PC12 Cells
  • Rats
  • Rats, Wistar
  • Receptor, trkA / antagonists & inhibitors*
  • Receptor, trkA / immunology
  • Receptor, trkA / metabolism
  • Receptors, Cholinergic / physiology*
  • Visual Cortex / cytology
  • Visual Cortex / growth & development
  • Visual Cortex / metabolism*

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Muscarinic Antagonists
  • Receptors, Cholinergic
  • Atropine
  • Nerve Growth Factor
  • Receptor, trkA
  • biocytin
  • Lysine