a kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity多巴胺的动力学模型和calcium-dependent纹状体突触可塑性.pdfVIP

A Kinetic Model of Dopamine- and Calcium-Dependent Striatal Synaptic Plasticity 1,2 3 1,2 1,2 Takashi Nakano , Tomokazu Doi , Junichiro Yoshimoto , Kenji Doya * 1 Graduate School of Information Science, Nara Institute of Science and Technology, Ikoma, Japan, 2 Okinawa Institute of Science and Technology, Uruma, Japan, 3 Osaka Bioscience Institute, Suita, Japan Abstract Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD), the combination with dopamine switches LTD to long-term potentiation (LTP), which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium- dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32), as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity.