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sss

Research

Molecular Mechanism and Controlling methods for Synaptic Plasticity

Background

The brain is the most complicated organelle and its function is mediated by the network of neurons. Neurons are composed of two distinct domains, dendrites and axons. Dendrite are innervated by axons, and this innervated points are called synapses. At the synapses, neurotransmitters are released from axon terminals, and the released neurotransmitters are received by the neurotransmitter receptors localized in dendrites. The most major excitatory neuronal transmission is mediated by the glutamates and the AMPA-type glutamate receptors. When the glutamate is released from the axon terminal of the pre-synaptic neuron, it binds to the AMPA-type glutamate receptor and opens this receptor channel which exist in the dendrite of the post-synaptic neuron. Then, the Na+ ions flow into the post-synaptic neuron, which induces the excitatory postsynaptic current (EPSC). By this mechanism information is transferred form the pre-synaptic neuron to post-synaptic neuron. Interestingly, the amplitude of EPSC, which means the efficiency of synaptic transmission, can be changed by neuronal activities. This phenomenon is called synaptic plasticity and thought to be one of the basis of memory and learning. We are trying to clarify the molecular mechanism of the synaptic plasticity and develop the controlling method of the synaptic plasticity.

Research

Recent studies have clarified that the intracellular trafficking of the AMPA-type glutamate receptor is the molecular basis of the synaptic plasticity. We have clarified that the Transmembrane AMPA receptor Regulatory Protein (TARP), which strongly bind to the AMPA receptor, associate with AP-2 and AP-3A, which plays essential roles for the trafficking of membrane proteins, in a dephosphorylation dependent manner. This dephosphorylation dependent binding between TARP and AP-2 and 3 play essential roles for the synaptic plasticity. We are now trying to identify the other TARP binding proteins and clarify the precise molecular mechanisms underlying synaptic plasticity. We also trying to develop the controlling method for synaptic plasticity, especially long-term depression (LTD). LTD is induced by the endocytosis of the AMPA receptor. We are generating the light sensitive endocytosis regulator and, by using this technique, we are trying to control brain function by light stimulation.

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