title: The BDNF Val66Met polymorphism enhances glutamatergic transmission but diminishes activity-dependent synaptic plasticity in the dorsolateral striatum.
abstract: The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene disrupts the activity-dependent release of BDNF, which might underlie its involvement in several neuropsychiatric disorders. Consistent with the potential role of regulated release of BDNF in synaptic functions, earlier studies have demonstrated that the BDNF Val66Met polymorphism impairs NMDA receptor-mediated synaptic transmission and plasticity in the hippocampus, the medial prefrontal cortex and the central amygdala. However, it is unknown whether the BDNF Val66Met polymorphism affects synapses in the dorsal striatum, which depends on cortical afferents for BDNF. Electrophysiological experiments revealed an enhanced glutamatergic transmission in the dorsolateral striatum (DLS) of knock-in mice containing the variant polymorphism (BDNFMet/Met) compared to the wild-type (BDNFVal/Val) mice. This increase in glutamatergic transmission is mediated by a potentiation in glutamate release and NMDA receptor transmission in the medium spiny neurons without any alterations in non-NMDA receptor-mediated transmission. We also observed an impairment of synaptic plasticity, both long-term potentiation and depression in the DLS neurons, in BDNFMet/Metmice. Thus, the BDNF Val66Met polymorphism exerts an increase in glutamatergic transmission but impairs synaptic plasticity in the dorsal striatum, which might play a role in its effect on neuropsychiatric symptoms. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Department of Psychiatry, Weill Medical College of Cornell University, New York, USA.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Jing
authors.affiliation: Department of Psychiatry, Weill Medical College of Cornell University, New York, USA.
authors.forename: Francis S
authors.initials: FS
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, NYU School of Medicine, New York, USA. Electronic address: Ipe.Ninan@nyumc.org.
authors.forename: Ipe
authors.initials: I
authors.lastname: Ninan
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D003712:Dendrites; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D055879:Gene Knock-In Techniques; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
keywords: BDNF Val66Met; Dorsal striatum; Glutamate; NMDA receptors; Synaptic plasticity