Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala

Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):8961-6. doi: 10.1073/pnas.1407018111. Epub 2014 Jun 2.

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.

Keywords: PcTX1; acid sensing ion channel; long-term potentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acid Sensing Ion Channel Blockers / chemistry
  • Acid Sensing Ion Channels / genetics*
  • Acidosis
  • Amygdala / metabolism
  • Amygdala / physiology*
  • Animals
  • Brain / metabolism
  • Electrodes
  • Excitatory Postsynaptic Potentials
  • Hydrogen-Ion Concentration
  • Ion Channels / chemistry
  • Learning
  • Long-Term Potentiation
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuronal Plasticity*
  • Neurons / metabolism
  • Neurotransmitter Agents / metabolism*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Peptides / chemistry
  • Protons*
  • Spider Venoms / chemistry
  • Synapses / physiology*

Substances

  • ASIC1 protein, mouse
  • ASIC2 protein, mouse
  • Acid Sensing Ion Channel Blockers
  • Acid Sensing Ion Channels
  • Ion Channels
  • Neurotransmitter Agents
  • PcTX1 protein, Psalmopoeus cambridgei
  • Peptides
  • Protons
  • Spider Venoms