title: Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala.
abstract: Stimulating presynaptic terminals can increase the proton concentration in synapses. Potential receptors for protons are acid-sensing ion channels (ASICs), Na(+)- and Ca(2+)-permeable channels that are activated by extracellular acidosis. Those observations suggest that protons might be a neurotransmitter. We found that presynaptic stimulation transiently reduced extracellular pH in the amygdala. The protons activated ASICs in lateral amygdala pyramidal neurons, generating excitatory postsynaptic currents. Moreover, both protons and ASICs were required for synaptic plasticity in lateral amygdala neurons. The results identify protons as a neurotransmitter, and they establish ASICs as the postsynaptic receptor. They also indicate that protons and ASICs are a neurotransmitter/receptor pair critical for amygdala-dependent learning and memory.
authors.affiliation: Howard Hughes Medical Institute andDepartment of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242;
authors.forename: Jianyang
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242;
authors.forename: Leah R
authors.initials: LR
authors.lastname: Reznikov
authors.affiliation: Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242;
authors.forename: Margaret P
authors.initials: MP
authors.lastname: Price
authors.affiliation: Department of Cell Biology and Neuroscience, University of South Alabama College of Medicine, Mobile, AL 36688;
authors.forename: Xiang-ming
authors.initials: XM
authors.lastname: Zha
authors.affiliation: Department of Psychiatry.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Central Microscopy Research Facility.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Moninger
authors.affiliation: Department of Psychiatry,Department of Neurosurgery,Department of Molecular Physiology and Biophysics, and Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA; andDepartment of Veterans Affairs Medical Center, Iowa City, IA 52246.
authors.forename: John A
authors.initials: JA
authors.lastname: Wemmie
authors.affiliation: Howard Hughes Medical Institute andDepartment of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242;Department of Neurosurgery,Department of Molecular Physiology and Biophysics, and Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA; and michael-welsh@uiowa.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000737:chemistry; D062565:Acid Sensing Ion Channels / Q000235:genetics*; D000138:Acidosis; D000679:Amygdala / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004566:Electrodes; D019706:Excitatory Postsynaptic Potentials; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000737:chemistry; D007858:Learning; D017774:Long-Term Potentiation; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry; D011522:Protons; D013111:Spider Venoms / Q000737:chemistry; D013569:Synapses / Q000502:physiology*
chemical_list: C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D007473:Ion Channels; D018377:Neurotransmitter Agents; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D011522:Protons; D013111:Spider Venoms
keywords: PcTX1; acid sensing ion channel; long-term potentiation