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.

中文翻译：

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BDNF Val66Met多态性对人运动皮层兴奋-抑制平衡和可塑性的影响

客观的

虽然之前的研究表明脑源性神经营养因子 (BDNF) 的单核苷酸多态性 (Val66Met) 可以影响神经可塑性，但 BDNF 基因型对皮质回路的影响以及与神经可塑性的关系在人类中仍然相对未探索。

方法

使用个性化的经颅磁刺激 (TMS) 参数，我们探讨了 BDNF Val66Met 多态性对兴奋性和抑制性神经回路的影响、其与 I 波 TMS (ITMS) 可塑性的关系以及对兴奋性/抑制性 (E/I) 平衡的影响在 18 个健康个体中。

结果

在 Met 等位基因携带者中，神经传递的兴奋性和抑制性指标降低。E/I 平衡很明显，这受 BDNF 的影响，Val/Val 纯合子的 E/I 比较高。Val/Val 纯合子的长期增强 (LTP-) 和抑制 (LTD-) 像 ITMS 可塑性都更大。通过增加刺激强度来补偿减少的兴奋性传递，在 Met 等位基因携带者中恢复了 LTP 而非 LTD 样效应。

结论

BDNF 基因型的影响可能从神经可塑性扩展到神经传递。E/I 平衡在人类运动皮层中很明显，由 BDNF 调节，可使用 TMS 测量。鉴于样本有限，这些初步调查结果值得进一步调查。

意义

这些新发现表明 BDNF 基因型对人类运动皮层的神经回路具有更广泛的作用。