Activity-dependent induction of tonic calcineurin activity mediates a rapid developmental downregulation of NMDA receptor currents

Neuron. 2000 Oct;28(1):103-14. doi: 10.1016/s0896-6273(00)00089-1.


Whole-cell recording in the superficial layers of the developing superior colliculus (sSC) reveals a large drop in NMDA receptor (NMDAR) current decay time synchronized across all neurons and occurring consistently between P10 and P11. We show that blocking the Ca2+/calmodulin-dependent phosphatase calcineurin (CaN) in the postsynaptic neuron can abolish this drop. The regulation is induced prematurely by 1-2 hr of electrical stimulation in P10 collicular slices only if CaN and NMDAR currents can be activated in the neuron. These data suggest that a long-lasting, CaN-mediated control of NMDAR kinetics is rapidly initiated by heightened activity of the NMDAR itself and demonstrate a novel developmental and tonic function of CaN that can play an important role in modulating the plasticity of the developing CNS.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Calcineurin / metabolism*
  • Calcineurin / pharmacology
  • Calcineurin Inhibitors
  • Dose-Response Relationship, Drug
  • Down-Regulation / genetics*
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / physiology
  • Gene Expression Regulation, Developmental / drug effects
  • In Vitro Techniques
  • Ion Transport / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / cytology
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Piperidines / pharmacology
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Superior Colliculi / cytology
  • Superior Colliculi / metabolism*
  • Synapses / metabolism
  • Tacrolimus / pharmacology


  • Calcineurin Inhibitors
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • NR1 NMDA receptor
  • NR2A NMDA receptor
  • NR2B NMDA receptor
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • Calcineurin
  • ifenprodil
  • Tacrolimus