Common marmosets, a primate, have various characteristics of higher brain functions that can be generalized directly to humans, such as higher cognitive functions and social behavior, in addition to their biological characteristics. Moreover, common marmosets are the only primate that can be used in research on genetic analysis and genetic modification; such research has been carried out mainly using rodents, which are frequently used in basic biology and medical research. Research in the field of brain science using common marmosets is expected to promote research on molecular biology related to human higher cognitive functions, social behavior, and emotions, which has been impossible in animal research using rodent models. In our laboratory, we aim to clarify the biological basis of the evolution of human cognition through experiments that focus on the relationships between cognitive functions and three factors, i.e., environment, genes, and neural basis.
We have already demonstrated that reorganization of intracortical connections involving gene expression is induced by tool-use training and causes the expansion of the related brain region of macaque monkeys owing to the learning of higher cognitive functions in association with tool-use training, which is rare for animals living in the wild. However, further clarification of the neurobiological mechanism underlying this brain regional expansion has been difficult using macaque monkeys. In our preliminary study, we found that a similar experimental system for a learned behavior can be directly applicable to common marmosets. We are currently establishing a research basis for the molecular genetics of higher cognitive functions of primates using this experimental system. We also aim to clarify the neural basis and functional mechanisms by focusing on voice-based communication as a method of observing the sociality of primates.
As the first step, noninvasive measurement of the volume of brain regions in one common marmoset is carried out over time by combining voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) methods to confirm the expansion of the cerebral cortices and thickening of the white matter in the brains of common marmosets that were trained to use tools. Then, we examined the cytogenetic biological basis of the changes in the volumes of the gray matter and white matter of the primate brains in association with the tool-use training. It has been considered that neurogenesis in adults is induced spontaneously in a certain brain region of primates; however, its credibility is still an issue. This will be solved in our experiments using common marmosets trained in order to learn higher cognitive functions. Total RNA is extracted from the expanded area of the brains of common marmosets that have learned the use of tools; changes in gene expression levels are analyzed using a marmoset-specific DNA microarray to search for and identify the gene clusters that show changes in expression levels associated with the use of tools. In addition, we will compare the gene expression patterns of known factor groups, such as the brain-derived neurotrophic factor (BDNF), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and cadherin family proteins, which are considered to be related to neural plasticity and synaptogenesis, between the groups of common marmosets with and without tool-use training.
After identifying the neurobiological mechanisms, we will determine the genetic factors underlying these mechanisms. This research is expected to clarify the mechanisms related to various psychological activities and mental disorders. We develop cognitive tasks for common marmosets in order to verify whether the human-specific neural circuitry generated by tool-use training or modification of human-specific genes underlies integration dysfunction syndrome and cognitive impairment of autism. By applying a test battery that can screen various cognitive functions, we analyze various parameters used in the new tasks that can detect interaction between sociality and cognitive functions in a cross-species approach. We also develop new tests to evaluate the behavioral and cognitive functions of common marmosets as a primate with a high sociality and cognitive capacity. These functions are considered to be universal higher brain functions that can be generalized to macaque monkeys and rodents. Our research will provide an effective behavioral analysis system for evaluating the biological analytical results of neural circuitry functions underlying behavior of these species from a cross-species viewpoint.
