Influence of BDNF Val66Met polymorphism on excitatory-inhibitory balance and plasticity in human motor cortex

•TMS measures of excitatory and inhibitory neurotransmission differed by BDNF Val66Met genotype.•An intrinsic balance between excitatory and inhibitory neurotransmission was evident and differed according to BNDF genotype.•In Met allele carriers, impaired LTP- but not LTD-like ITMS plasticity was restored by calibrating for reductions in excitatory transmission. While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human. Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals. Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP- but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission. The influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation. These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex.