Investigation de l’effet du polymorphisme Val66Met du gène BDNF sur les mécanismes neurophysiologiques qui sous-tendent les apprentissages moteurs procéduraux et sensorimoteurs, de même que sur le transfert intermanuel des apprentissages

Brain-derived neurotrophic factor (BDNF), which is largely synthesized in glutamatergic neurons in response to stimulation, is involved in synaptic plasticity and dendritic growth, and plays a key role in development, function, and survival of neurons in the central nervous system. The BDNF gene is most commonly found in its Valine to Valine form at codon 66 (Val66Val). The single nucleotide Val66Met polymorphism, found in approximately one third of the American population, interferes with BDNF recapture in the secretory vesicles, thus altering BDNF availability in the synaptic cleft and dendrites. Thus, the Val66Met polymorphism is associated with altered excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, synaptogenesis, and functional and structural alterations of several brain structures compared to Val66Val carriers, for instance, at the level of the hippocampus. In the primary motor cortex, the Val66Met polymorphism is linked to altered activity-dependent synaptic plasticity, which may be expressed in impaired regulation of motor cortical maps, corticospinal excitability, and synaptic homeoplasticity. At the behavioral level, Val66Met carriers display impaired learning and retention of complex visuomotor skills. However, to this day, little is known regarding the effects of the Val66Met polymorphism on intracortical plasticity mechanisms involved in motor learning, and intermanual transfer of a motor skill, which relies in part on interhemispheric interactions.  In the present work, we compared learning, retention and intermanuel transfer of procedural motor skills on the Serial Reaction Time Task (SRTT), and learning of basic sensorimotor components, namely muscle contraction speed, precision grip strength, and fine manual dexterity, between Val66Val and Val66Met right-handed participants aged between 18 and 35 years old. Transcranial magnetic stimulation was used to compare the underlying neurophysiological mechanisms in M1, corticospinal excitability, short intracortical inhibition, and interhemispheric inhibition. Results of the two studies suggested the absence of difference in basic sensorimotor skill learning with the right dominant hand and the left non-dominant hand, and in procedural motor learning between Val66Val and Val66Met carriers. Further, the results in study 1 indicated an impaired intermanual transfer of procedural skills from the dominant learning hand to the non-dominant untrained hand in the Val66Met group, which likely suggests altered interhemispheric interactions. Moreover, the results in study 2 showed an absence of short-intracortical inhibition in bilateral M1 among Val66Met carriers following sensorimotor learning. Potential implications of these results in the interaction between the Val66Met polymorphism, motor learning, and the underlying neurophysiological mechanisms are discussed. In sum, these results provide a more in-depth perspective of the relationship between the Val66Met polymorphism and these processes, and specific hypotheses for future studies.

Keyphrases: Brain-derived neurotrophic factor, Val66Met polymorphism, motor learning, intermanual transfer, primary motor cortex, transcranial magnetic stimulation, corticospinal excitability, short intracortical inhibition, interhemispheric inhibition