The signaling protein G-substrate modulates motor learning of the eyes during different stages of postnatal development
An international team of scientists, led by Shogo Endo at the Okinawa Institute of Science and Technology and Masao Ito at the RIKEN Brain Science Institute in Wako, has shown that deletion of the G-substrate gene in mice causes motor learning deficits during particular periods of postnatal development (1). According to Ito, this research “required ten years of collaboration between ten different laboratories.”
Purkinje neurons, found in the part of the brain known as the cerebellum, contribute to regulating the learning of motor skills, such as riding a bicycle (Fig. 1). G-substrate is a signaling protein found within cerebellar Purkinje neurons. Previous work by these researchers had shown that G-substrate, when activated, inhibits enzymes called phosphatases, which remove phosphate groups from a variety of proteins in the cell. However, the functional role of G-substrate in behavior in living animals was unknown.
Endo, Ito and colleagues found that animals lacking the G-substrate gene had normal brain structure and overall locomotor behavior, but had deficits in a type of motor learning called the optokinetic eye movement response (OKR).
In the OKR test, the researchers tracked the eye movements of a mouse as it observes a checkered screen that is oscillating. After an hour of exposure to the screen, normal six-week-old mice have an increased eye movement response. However, this ‘short-term OKR adaptation’ was absent in six-week-old mice missing the G-substrate gene.
Surprisingly, at earlier and later developmental stages, this short-term OKR adaptation was equivalent in normal mice and in mice lacking the G-substrate gene. This specific motor learning deficit observed at 6 weeks of age in mice missing the G-substrate gene corresponds to the developmental stage during which these mice also had deficits in synaptic plasticity within the cerebellum. This suggests that synaptic plasticity plays a key role in regulating short-term OKR adaptation.
In twelve-week-old mice lacking the G-substrate gene, short-term adaptation was normal but there were deficits in long-term OKR adaptation. These mice were exposed to the oscillating screen for an hour per day over five days, and the eye movement responses were measured at the end of that period. In spite of this particular deficit, other types of motor learning seemed normal in the mice missing the gene for G-substrate.
These findings suggest that multiple signaling pathways are operating during development to regulate different types of motor learning. Ito says the data also “provide strong support for the hypothesis that synaptic plasticity is causally linked to motor learning.”
Reference
1. Endo, S., Shutoh, F., Dinh, T.L., Okamoto, T., Ikeda, T., Suzuki, M., Kawahara, S., Yanagihara, D., Sato, Y., Yamada, K., et al., Dual involvement of G-substrate in motor learning revealed by gene deletion. Proceedings of the National Academy of Sciences USA 106, 3525–3530 (2009).
The corresponding author for this highlight is based at the RIKEN Laboratory for Memory and Learning
