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The prototoxin lynx1 acts on nicotinic acetylcholine receptors to balance neuronal activity and survival in vivo.

Nicotinic acetylcholine receptors (nAChRs) affect a wide array of biological processes, including learning and memory, attention, and addiction. lynx1, the founding member of a family of mammalian prototoxins, modulates nAChR function in vitro by altering agonist sensitivity and desensitization kinetics. Here we demonstrate, through the generation of lynx1 null mutant mice, that lynx1 modulates nAChR signaling in vivo. Its loss decreases the EC(50) for nicotine by approximately 10-fold, decreases receptor desensitization, elevates intracellular calcium levels in response to nicotine, and enhances synaptic efficacy. lynx1 null mutant mice exhibit enhanced performance in specific tests of learning and memory. Consistent with reports that mutations resulting in hyperactivation of nAChRs can lead to neurodegeneration, aging lynx1 null mutant mice exhibit a vacuolating degeneration that is exacerbated by nicotine and ameliorated by null mutations in nAChRs. We conclude that lynx1 functions as an allosteric modulator of nAChR function in vivo, balancing neuronal activity and survival in the CNS.

Pubmed ID: 16950157


  • Miwa JM
  • Stevens TR
  • King SL
  • Caldarone BJ
  • Ibanez-Tallon I
  • Xiao C
  • Fitzsimonds RM
  • Pavlides C
  • Lester HA
  • Picciotto MR
  • Heintz N



Publication Data

September 7, 2006

Associated Grants

  • Agency: NIAAA NIH HHS, Id: AA 15632
  • Agency: NCI NIH HHS, Id: CA 09673
  • Agency: NIDA NIH HHS, Id: DA 00436
  • Agency: NIDA NIH HHS, Id: DA 15241
  • Agency: NIDA NIH HHS, Id: DA 17279
  • Agency: NINDS NIH HHS, Id: R21 NS 047751

Mesh Terms

  • Age Factors
  • Animals
  • Association Learning
  • Brain
  • Cell Survival
  • Excitatory Amino Acid Agonists
  • Membrane Glycoproteins
  • Membrane Potentials
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Nerve Degeneration
  • Neurons
  • Neuropeptides
  • Nicotine
  • Nicotinic Agonists
  • Patch-Clamp Techniques
  • Receptors, Nicotinic