Interaction of NMDA receptors and L-type calcium channels during early odor preference learning in rats

Eur J Neurosci. 2012 Oct;36(8):3134-41. doi: 10.1111/j.1460-9568.2012.08210.x. Epub 2012 Jul 5.


Early odor preference learning in rats provides a simple model for studying learning and memory. Learning results in an enhanced output from mitral cells, which carry odor information from the olfactory bulb to the olfactory cortex. Mitral cell NMDA receptors (NMDARs) are critically involved in plasticity at the olfactory nerve to mitral cell synapse during odor learning. Here we provide evidence that L-type calcium channels (LTCCs) provide an additional and necessary source of calcium for learning induction. LTCCs are thought to act downstream of NMDARs to bridge synaptic activation and the transcription of the plasticity-related proteins necessary for 24-h learning and memory. Using immunohistochemistry, we have demonstrated that LTCCs are present in the mitral cell and are primarily located on mitral cell proximal dendrites in neonate rats. Behavioral experiments demonstrate that inhibiting the function of LTCCs via intrabulbar infusion of nimidopine successfully blocks learning induced by pairing isoproterenol infusion with odor, while activation of LTCCs via an intrabulbar infusion of BayK-8644 rescues isoproterenol-induced learning from a D-APV block. Interestingly, the infusion of BayK-8644 paired with odor is by itself not sufficient to induce learning. Synaptoneurosome Western blot and immunohistochemistry measurement of synapsin I phosphorylation following BayK-8644 infusion suggest LTCCs are involved in synaptic release. Finally, odor preference can be induced by gabazine disinhibition of mitral cells, and NMDAR opening is sufficient for the gabazine-induced learning. These results provide the first evidence that NMDARs and LTCCs interact to permit calcium-dependent mitral cell plasticity during early odor preference learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Dendrites / metabolism
  • Gene Expression
  • Isoproterenol / pharmacology
  • Learning*
  • Neuronal Plasticity
  • Nimodipine / pharmacology
  • Odorants*
  • Olfactory Bulb / metabolism
  • Olfactory Perception
  • Pyridazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapsins / metabolism
  • Transcription, Genetic


  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Pyridazines
  • Receptors, N-Methyl-D-Aspartate
  • Synapsins
  • Nimodipine
  • 2-Amino-5-phosphonovalerate
  • gabazine
  • Isoproterenol
  • Calcium