ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory

Sci Rep. 2015 May 19:5:10143. doi: 10.1038/srep10143.

Abstract

Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both fear learning and activity-induced long-term potentiation (LTP) of cortico-basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting a critical role of ASICs in fear memory formation. In this study, we found that ASICs were differentially expressed within the amygdala neuronal population, and the extent of LTP at various glutamatergic synapses correlated with the level of ASIC expression in postsynaptic neurons. Importantly, selective deletion of ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in these cells and reduced fear learning to the same extent as that found when ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear learning requires ASIC-dependent LTP at multiple amygdala synapses, including both cortico-BLA input synapses and intra-amygdala synapses on output neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / biosynthesis
  • Acid Sensing Ion Channels / genetics*
  • Amygdala / metabolism*
  • Animals
  • Excitatory Postsynaptic Potentials / physiology*
  • Fear / physiology*
  • Fear / psychology
  • Female
  • GABAergic Neurons / physiology
  • Learning
  • Long-Term Potentiation / physiology*
  • Male
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity / physiology
  • Synapses / metabolism

Substances

  • ASIC1 protein, mouse
  • Acid Sensing Ion Channels