Influence of BDNF Val66Met polymorphism on excitatory-inhibitory balance and plasticity in human motor cortex |
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| Affiliation: | 1. Division of Neurology, Department of Medicine, University of Toronto and Krembil Brain Institute, Toronto, Ontario, Canada;2. Melbourne Neuropsychiatry Centre, The University of Melbourne, Victoria 3010, Australia;3. Department of Biomedical Engineering, The University of Melbourne, Victoria 3010, Australia;4. Dept of Neurophysiology, NIMHANS, Bengaluru, India;5. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada;6. Department of Psychiatry, UC San Diego Health, San Diego, CA 92093, USA |
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| Abstract: | ObjectiveWhile 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.MethodsUsing 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.ResultsExcitatory 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.ConclusionsThe 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.SignificanceThese novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex. |
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| Keywords: | BDNF Excitatory-inhibitory balance TMS ITMS SICF APB" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" abductor pollicis brevis BDNF" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" brain-derived neurotrophic factor CS" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" Conditioning Stimulus E/I balance" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" balance in the strength of excitatory and inhibitory circuitry EMG" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" electromyography ISI" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" interstimulus interval ITMS" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" I-wave TMS LICI" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" long interval intracortical inhibition LTP" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" long-term potentiation LTD" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" long-term depression MEP" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" motor evoked potential RMT" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" resting motor threshold SICF" },{" #name" :" keyword" ," $" :{" id" :" k0155" }," $$" :[{" #name" :" text" ," _" :" short interval intracortical facilitation SICI" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" short interval intracortical inhibition, TMS, transcranial magnetic stimulation |
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