The V
al66M
et polymorphism in the brain-derived neurotrophic factor (BDNF) gene disrupts the activity-dependent release of BDNF, which might underlie its involvement in sever
al neuropsychiatric disorders. Consistent with the potenti
al role of regulated release of BDNF in synaptic functions, earlier studies have demonstrated that the BDNF V
al66M
et polymorphism impairs NMDA receptor-mediated synaptic transmission and plasticity in the hippocampus, the medi
al prefront
al cortex and the centr
al amygd
ala. However, it is unknown wh
ether the BDNF V
al66M
et polymorphism affects synapses in the dors
al striatum, which depends on cortic
al afferents for BDNF. Electrophysiologic
al experiments reve
aled an enhanced glutamatergic transmission in the dorsolater
al striatum (DLS) of knock-in mice containing the variant polymorphism (BDNF
Met/Met) compared to the wild-type (BDNF
Val/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 BDNF
Met/Met mice. Thus, the BDNF V
al66M
et polymorphism exerts an increase in glutamatergic transmission but impairs synaptic plasticity in the dors
al striatum, which might play a role in its effect on neuropsychiatric symptoms.
This article is part of the Special Issue entitled ‘Ionotropic glutamate receptors’.