Autism spectrum disorder (ASD) is a set of heterogenous neurodevelopmental conditions that is characterized by persistent deficits in social communication and social interaction, as well as restricted, repetitive patterns of behavior, interests, or activities. Despite increasing attention, the physiological mechanisms underlying cognitive behavioral features in ASD are unknown. A Japanese research team led by Masaki Isoda and others has now demonstrated that there might be a paucity of nerve cells (neurons) in the autistic brain that process other individuals’ actions.

   The team noticed that one of their research monkeys (named monkey E) behaved differently from others: it displayed an impaired ability to interactively perform a turn-taking task with other monkeys, the lack of social communication with human experimenters, and repetitive behavior, which are most frequently associated with ASD. The researchers then recorded activity of single neurons while the monkeys performed the turn-taking task. In this way they were able to determine the neuronal basis whereby monkey E displayed poor ability to monitor others’ actions, explains Isoda. “We found that in monkey E, neurons responding to others’ actions, abundant in the controls, were almost nonexistent.”

   The researchers then carried out an extensive genomic analysis, known as copy number variation and exome sequencing methods. “Monkey E had rare coding variants in two genes that are associated with human neurodevelopmental and psychiatric disorders,” says Isoda. “We considered that monkey E had a particular disorder that could be called psychiatric, similar to human ASD.”

   Having identified the world’s first case of naturally occurring ASD in nonhuman primates, Isoda now wants to delve deeper into the underlying process. “The next step will be to develop a nonhuman primate model of ASD by manipulating gene expressions in the macaque brain. The genetic variants identified in the present study will be a good target for that purpose.”

 

Questions

Extra information 1: What is interesting to you about this topic?

A neuropsychiatric condition that is best described as ASD can exist in nonhuman primates.

Extra information 2: Did something surprise you when you did this study and analyzed your results?

What surprised us is the electrophysiological finding that medial frontal neurons responding to others’ actions, abundant in the controls, were almost nonexistent in the autistic monkey.

 

Collaborative Researchers

 

Name: Kyoko Yoshida

Department: Division of Neurosurgery

Institute: Japan Community Healthcare Organization Yugawara Hospital

 

Name: Yasuhiro Go

Department: Department of Brain Sciences

Institute: Center for Novel Science Initiatives, National Institutes of Natural Sciences

 

Name: Itaru Kushima, Norio Ozaki

Department: Department of Psychiatry

Institute: Nagoya University Graduate School of Medicine

 

Name: Atsushi Toyoda, Asao Fujiyama

Department: Comparative Genomics Laboratory

Institute: National Institute of Genetics

 

Name: Hiroo Imai

Department: Molecular Biology Section

Institute: Primate Research Institute, Kyoto University

 

Name: Nobuhito Saito

Department: Department of Neurosurgery

Institute: The University of Tokyo Graduate School of Medicine

 

Name: Atsushi Iriki

Department: Laboratory for Symbolic Cognitive Development

Institute: RIKEN Brain Science Institute

 

Funding

This work was supported by a Grant-in-Aid for Japan Society for the Promotion of Science (JSPS) Fellows; a Grant-in-Aid for Scientific Research for Innovative Areas “Genome Science”; National Institutes of Natural Sciences program for cross-disciplinary study; “Integrated research on neuropsychiatric disorders” carried out under the Strategic Research Program for Brain Sciences and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from Japan Agency for Medical Research and development, AMED; Precursory Research for Embryonic Science and Technology; the Brain Sciences Project of the Center for Novel Science Initiatives, the National Institutes of Natural Sciences; and in part by JSPS KAKENHI.