A molecular mechanism for stabilization of learning-induced synaptic modifications

Neuron. 2004 Jan 22;41(2):185-92. doi: 10.1016/s0896-6273(03)00874-2.


Olfaction is a principal sensory modality in rodents, and rats quickly learn to discriminate between odors and to associate odor with reward. Here we show that such olfactory discrimination (OD) learning consists of two phases with distinct cellular mechanisms: an initial NMDAR-sensitive phase in which the animals acquire a successful behavioral strategy (rule learning), followed by an NMDAR-insensitive phase in which the animals learn to distinguish between individual odors (pair learning). Rule learning regulates the composition of synaptic NMDARs in the piriform cortex, resulting in receptors with a higher complement of the NR2a subunit protein relative to NR2b. Rule learning also reduces long-term potentiation (LTP) induced by high-frequency stimulation of the intracortical axons in slices of piriform cortex. As NR2a-containing NMDARs mediate shorter excitatory postsynaptic currents than those containing NR2b, we suggest that learning-induced regulation of NMDAR composition constrains subsequent synaptic plasticity, thereby maintaining the memory encoded by experience.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology
  • Discrimination Learning / drug effects
  • Discrimination Learning / physiology*
  • Dizocilpine Maleate / pharmacology
  • Electrophysiology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / physiology
  • Immunoblotting
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Male
  • Memory / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Reward
  • Smell / physiology
  • Synapses / drug effects
  • Synapses / physiology*


  • Excitatory Amino Acid Antagonists
  • NR2A NMDA receptor
  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate