Alteration of the Centromedial Amygdala Glutamatergic Synapses by the BDNF Val66Met Polymorphism. Academic Article uri icon

Overview

abstract

  • Fear expression is mediated by an activation of the centromedial amygdala (CEm), the major output nucleus of the amygdaloid complex. Consistently, fear extinction is associated with an increased synaptic inhibition as well as a suppression of the excitability of the CEm neurons. However, little is known about the role of CEm glutamatergic synapses in fear regulation and anxiety-like behaviors. The BDNF Val66Met, a single-nucleotide polymorphism in the human BDNF gene, impairs fear extinction and leads to anxiety-like symptoms. To determine whether the BDNF Val66Met polymorphism affects the CEm excitatory synapses, we examined basal glutamatergic synaptic transmission and plasticity in the CEm neurons of BDNF Val66Met knock-in (BDNF(Met/Met)) mice. The BDNF Val66Met single-nucleotide polymorphism exerted an opposite effect on non-NMDA and NMDA receptor transmission with a potentiation of the former and a suppression of the latter. In addition, the decay time of NMDA currents was decreased in BDNF(Met/Met) mice, suggesting a modification of NMDA receptor subunit composition. Unlike the wild-type mice that exhibited a potentiation of non-NMDA receptor transmission following fear conditioning and a depotentiation upon fear extinction, BDNF(Met/Met) mice failed to show this experience-dependent synaptic plasticity in the CEm neurons. Our results suggest that the elevated non-NMDA receptor transmission, the suppression of NMDA receptor transmission, and an impairment of synaptic plasticity in the CEm neurons might contribute to the fear extinction deficit and increased anxiety-like symptoms in BDNF Val66Met carriers.

publication date

  • March 18, 2015

Research

keywords

  • Brain-Derived Neurotrophic Factor
  • Central Amygdaloid Nucleus
  • Glutamic Acid
  • Neurons
  • Polymorphism, Single Nucleotide
  • Synapses

Identity

PubMed Central ID

  • PMC4613621

Scopus Document Identifier

  • 84937164360

Digital Object Identifier (DOI)

  • 10.1038/npp.2015.76

PubMed ID

  • 25786582

Additional Document Info

volume

  • 40

issue

  • 9