News Releases & Research Results Discovery of a novel model of neural circuitry in basal ganglia involved in motor control: Interaction between direct and indirect pathways

The results of research conducted by Associate Professor Hiroyuki Hioki and Research Assistant Shinichiro Okamoto of the Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, and others.

• Regarding signal transduction in the basal ganglia (*1), the research group discovered a novel mode of innervation involving the direct and indirect pathways (*2).
  (*1) The basal ganglia constitute a group of nuclei, including the striatum and the external segment of the globus pallidus, which forms an important part of the brain that controls various functions, including motor function, learning, and emotions.
  (*2) The two pathways are responsible for signal transduction in the basal ganglia: the direct pathway delivers information related to movement initiation, whereas the indirect pathway delivers information to suppress movement.
• In particular, a new adeno-associated virus (AAV) vector that expresses green fluorescent protein (GFP) and red fluorescent protein (RFP) in the presence and absence of "Cre recombinase," respectively, a protein that mediates site-specific DNA recombination, was developed. By injecting this AAV vector into the neostriatum of transgenic mice that expressed "Cre recombinase" only in direct pathway neurons, GFP and RFP were successfully expressed in the direct and indirect pathway neurons, respectively, to simultaneously visualize and distinguish the direct and indirect pathways, for the first time in the world.
• The results of this study can potentially improve the understanding of the motor functions of the brain, which will help elucidate motor dysfunction observed in Parkinson’s disease and in other conditions and their pathogenesis in greater detail, and aid the development of novel therapeutic modalities for their treatment.

This program was conducted with support from the Brain Mapping by Integrated Neurotechnologies for Disease Studies by AMED.

The results of this research project were published in iScience on September 2.

Okamoto S., et al. Overlapping Projections of Neighboring Direct and Indirect Pathway Neostriatal Neurons to Globus Pallidus External Segment iScience
DOI：10.1016/j.isci.2020.101409