The Relation Between Long-Term Synaptic Plasticity at Glutamatergic Synapses in the Amygdala and Fear Learning in Adult Heterozygous BDNF-Knockout Mice

Cereb Cortex. 2018 Apr 1;28(4):1195-1208. doi: 10.1093/cercor/bhx032.

Abstract

Brain-derived neurotrophic factor (BDNF) heterozygous knockout mice (BDNF+/- mice) show fear learning deficits from 3 months of age onwards. Here, we addressed the question how this learning deficit correlates with altered long-term potentiation (LTP) in the cortical synaptic input to the lateral amygdala (LA) and at downstream intra-amygdala synapses in BDNF+/- mice. Our results reveal that the fear learning deficit in BDNF+/- mice was not paralleled by a loss of LTP, neither at cortical inputs to the LA nor at downstream intra-amygdala glutamatergic synapses. As we did observe early fear memory (30 min after training) in BDNF+/- mice while long-term memory (24 h post-training) was absent, the stable LTP in cortico-LA and downstream synapses is in line with the intact acquisition of fear memories. Ex vivo recordings in acute slices of fear-conditioned wildtype (WT) mice revealed that fear learning induces long-lasting changes at cortico-LA synapses that occluded generation of LTP 4 and 24 h after training. Overall, our data show that the intact LTP in the tested amygdala circuits is consistent with intact acquisition of fear memories in both WT and BDNF+/- mice. In addition, the lack of learning-induced long-term changes at cortico-LA synapses in BDNF+/- mice parallels the observed deficit in fear memory consolidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / cytology*
  • Animals
  • Brain-Derived Neurotrophic Factor / deficiency*
  • Brain-Derived Neurotrophic Factor / genetics
  • Carbazoles / pharmacology
  • Cerebral Cortex / physiology
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Evoked Potentials / genetics
  • Fear / physiology*
  • GABA Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Indole Alkaloids / pharmacology
  • Learning / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / drug effects
  • Patch-Clamp Techniques
  • Pyridazines / pharmacology

Substances

  • Brain-Derived Neurotrophic Factor
  • Carbazoles
  • Enzyme Inhibitors
  • GABA Antagonists
  • Indole Alkaloids
  • Pyridazines
  • Glutamic Acid
  • staurosporine aglycone
  • gabazine