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Influence of BDNF Val66Met polymorphism on excitatory-inhibitory balance and plasticity in human motor cortex
R F H Cash1, K Udupa2, C A Gunraj3
1Division of Neurology, Department of Medicine, University of Toronto and Krembil Brain Institute, Toronto, Ontario, Canada; Melbourne Neuropsychiatry Centre, The University of Melbourne, Victoria 3010, Australia; Department of Biomedical Engineering, The University of Melbourne, Victoria 3010, Australia.
Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Significance:
These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex.
