Heterosynaptic long-term potentiation at interneuron-principal neuron synapses in the amygdala requires nitric oxide signalling

J Physiol. 2012 Jan 1;590(1):131-43. doi: 10.1113/jphysiol.2011.221317. Epub 2011 Oct 31.


Long-lasting changes of synaptic efficacy are thought to be a prerequisite for memory formation and maintenance. In the basolateral complex of the amygdala (BLA), one of the main regions for fear and extinction learning of the brain, various forms of long-term potentiation (LTP) have been described for excitatory glutamatergic synapses. In contrast, little is known about the mechanisms of LTP at inhibitory GABAergic synapses. Here we provide evidence that (1) LTP at inhibitory GABAergic synapses (LTP(i)) between inhibitory interneurons and principal neurons (PNs) can be induced by theta-burst stimulation (TBS), (2) this LTP(i) is prevented by AMPA- or NMDA-receptor antagonists, and (3) this LTP(i) is abolished by the NO synthase (NOS) inhibitor L-NAME or the NO scavenger PTIO, and thus is critically dependent on nitric oxide (NO) signalling. These findings are corroborated by immunocytochemical stainings for neuronal (n) NOS, which revealed the existence of nNOS-positive neurons and fibres in the BLA. We conclude that LTP of GABAergic synaptic transmission to PNs is induced by activation of AMPA and NMDA receptors at glutamatergic synapses and subsequent retrograde NO signalling to enhance GABAergic transmission. This form of LTP at GABAergic synapses comprises a novel form of heterosynaptic plasticity within the BLA, apt to shape conditioned fear responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Amygdala / physiology*
  • Animals
  • Fear / physiology
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Long-Term Potentiation / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Fibers / metabolism
  • Nerve Fibers / physiology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / metabolism
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction
  • Synapses / metabolism
  • Synapses / physiology*
  • Synaptic Potentials / physiology
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism


  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Nitric Oxide
  • gamma-Aminobutyric Acid
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse