Laboratory Head
Kanato Yamagata
We study the molecular basis of activity-dependent synaptic plasticity. In particular, we have cloned a set of immediate early genes (IEGs) that are rapidly transcribed in neurons involved in information processing, and that are essential for long term memory. IEG proteins can directly modify synapses and provide insight into cellular mechanisms that support synaptic plasticity. Furthermore, these IEG products have been shown to be involved in developmental brain disorders, including refractory epilepsy, intellectual disability and/or autism.
“We have clarified mechanisms of refractory epilepsy, intellectual disability and/or autism caused by impaired synaptic plasticity. Based on the novel mechanisms we found, we are trying to find new treatments for developmental brain disorders”
For example, COX-2 and mPGES-1 are prostaglandin synthases that exacerbate neuronal cell death after seizures, leading to intractable epilepsy. Arcadlin is a protocadherin that induces spine shrinkages after seizures, resulting in developmental delay or amnesia. Rheb regulates excitatory synapse formation via syntenin. Constitutive activation of Rheb causes TSC (tuberous sclerosis complex), which is accompanied by epilepsy, mental retardation and autism. Finally, neuritin is a secreted or membrane-anchored protein and induces neurite branching. It may be involved in temporal lobe epilepsy. Thus, analysis of rapid de novo transcription provides novel insights into the cellular and neural network basis of behavioral plasticity.
We are also exploring the possibility that these IEG products could be therapeutic targets for developmental disorders. We are making genetic mouse models of developmental disorders and are testing the effects of several drug inhibitors against IEGs.
Laboratory Head Kanato Yamagata