The BDNF Val66Met polymorphism enhances glutamatergic transmission but diminishes activity-dependent synaptic plasticity in the dorsolateral striatum

NEUROPHARMACOLOGY

卷:112

Article

Jing, Deqiang¹  Lee, Francis S.¹  Ninan, Ipe² 

[1] Cornell Univ, Dept Psychiat, Weill Med Coll, New York, NY 10021 USA

[2] NYU, Sch Med, Dept Psychiat, 450 East 29th St, New York, NY 10016 USA

关键词: Dorsal striatum;    BDNF Val66Met;    NMDA receptors;    Synaptic plasticity;    Glutamate;   

DOI  :  10.1016/j.neuropharm.2016.06.030

来源: Elsevier

【 摘 要 】

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/Met mice. 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'. (C) 2016 Elsevier Ltd. All rights reserved.

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