Activity-dependent induction of tonic calcineurin activity mediates a rapid developmental downregulation of NMDA receptor currents.
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.
Shi
J
J
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Townsend
M
M
Constantine-Paton
M
M
D000200:Action Potentials / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism* / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000235:genetics*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013477:Superior Colliculi / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin; C010739:ifenprodil; D016559:Tacrolimus