A surgical method for complete interhemispheric corpus callosotomy combined with extended frontoparietal craniotomy in mouse

Abstract Callosotomy is an invasive method that is used preclinically to study the role of interhemispheric functional connectivity in the brain. In small animals, it is technically challenging to perform. To date, there exists two main approaches for transecting the corpus callosum in rodents: trephine hole(s) or unilateral craniotomy. Both of these approaches will cause damage to other brain structures, mainly the cerebral cortex, or injury of large vessels, such as the superior sinus, that may lead to intracranial hemorrhage and animal death. In this study, we present a novel approach for complete corpus callosotomy in adult mice using an interhemispheric approach combined with bilateral and extended craniotomy across the midline. This study demonstrated that bilateral and extended craniotomy provided the visual space required for hemisphere and sinus retraction, thus keeping large blood vessels and surrounding brain structures intact during transection of the corpus callosum under surgical microscope using fine, standardized surgical instruments. We also emphasized the importance of good post-operative care leading to optimal recovery, increasing overall animal survival, and reducing the number of animals used in the experiments, which are crucial in conducting long-term studies. Taken together, this approach can provide higher reproducibility and smaller variability of study results among animals, including long-term behavioral studies in mice. This novel interhemispheric approach to complete callosotomy will facilitate further studies, helping to extend knowledge of the corpus callosum in interhemispheric transfer and its role in various neurological and psychiatric pathologies.