[PhD Thesis Presentation] -Masakazu Igarashi- The role of interhemispheric cortico-cortical connections in bimanual coordination in the rats

Abstract

Title: The role of interhemispheric cortico-cortical connections in bimanual coordination in
the rats

Bimanual coordination – in which both hands work together to achieve a goal – is crucial for basic needs of life, such as gathering and feeding. The mammalian body has a left and right side which is often symmetrical shape, but raises the question of how does the brain organize two side of our body in coordinated manner. The overall aim of this thesis is to betterunderstand neural mechanism of bimanual coordination. Bimanual coordination is highly developed in primates, where it has been most extensively studied. Rodents also exhibit remarkable dexterity and coordination of forelimbs during food handling and consumption. However, rodents have been less commonly used in the study of bimanual coordination because of limited quantitative measuring techniques. To study the neural mechanism of bimanual coordination using rodents, therefore, first require method to measure and classify bimanual
movements. In this thesis, I propose a high-resolution tracking system that enables kinematic analysis of rat forelimb movement. The system quantifies forelimb movements bilaterally in head-fixed rats during food handling and consumption. Forelimb movements occurring naturally during feeding were encoded as continuous 3-D trajectories. The trajectories were then automatically segmented and analyzed, using a novel algorithm, according to the laterality of movement speed or the asymmetry of movement direction across the forelimbs. Bilateral forelimb movements were frequently observed during spontaneous food handling. Both symmetry and asymmetry in movement direction were observed, with symmetric bilateral movements quantitatively more common. Using the proposed method, I further investigated a key hypothesis that the corpus callosum, the thickest commissure connecting two cerebral cortices, mediates bimanual movements. I performed pharmacological blockade of the anterior corpus callosum (aCC) in which commissures from cortical forelimb motor areas run through. The kinematic analysis of bimanual coordination during food handling revealed that the frequency of occurrence of symmetric bimanual movements was reduced by aCC inhibition. In counterpart, asymmetric bimanual movements were increased. Other global scales of motor skills, such as mean food drop rate, and mean consumption time remained unchanged. Bilateral multiunit recordings from corresponding cortical areas showed positively correlated activity patterns in the large majority of interacting pairs. Present study also found that the putative excitatory neurons were also positively correlated with putative inhibitory neurons in opposite hemisphere, suggesting interhemispheric inhibition via inhibitory neurons. Collectively, these results suggest that the symmetric bimanual movements in rodents are modulated by the anterior corpus callosum via both excitatory and inhibitory connections of two motor cortices.