Kinetics Of Signal Transduction Networks On Neural Synaptic Plasticity

It is widely believed that intracellular signal transduction associated with synap-tic plasticity have very important significance for the senior cognitive function such as learning and memory. Recently, the research of this field has achieved rapid develop-ment. With the increasingly emergence of the experimental data and the continuously refinement of the signal pathways, signal transduction networks become more and more complex. Therefore, researchers need to have rich knowledge of this field and recog-nize the intracellular signal transduction system from the view of the whole networks. Moreover, research tools and means must also switch from single technology and dis-cipline to multi-technologies and interdisciplinary studies in order to understand and grasp its dynamic panorama more deeply. In this dissertation, we developed the dy-namic model based on the present classical experimental results and data to quantita-tively investigate and analyze the kinetics of signal transduction networks depended on CREB and associated with neural synaptic plasticity.Transcription factor CREB plays an important role for neural synaptic plasticity related with learning and memory. In chapter3, a dynamic model about the cAMP-PKA-CREB signal pathway was constructed, in which a CREB-dependent positive feedback loop was first inserted into this pathway by assuming CREB-dependent gene transcription and protein synthesis to positively regulate upstream pathways. Results showed that the model was a bistable system and CREB-dependent positive feedback loop might be essential for the bistability. Our results also suggest that this positive feedback loop may be one of the oriented mechanisms which determines the induction and maintenance of LTP.On the basis of the above-developed model, we further presented a detailed bio-chemical model that combines both the membrane electric behaviors of single neu-ron and the interaction to the nucleus CREB to systematically investigate the intrin-sic mechanisms and dynamic properties between LTP/LTD and CREB-dependent cas-cades. Using the proposed model, we qualitatively reproduced LTP/LTD by different induction protocols such as varying the rate presynaptic stimulation and the time of pre-and post-synaptic action potentials. And the model, the first one in the literature to attempt to link nucleus dynamics to the membrane electric behaviors, predicts that CREB1/2-dependent positive and negative feedback mechanisms might play a key role for the bidirectional synaptic plasticity. It is important to note here that the above-proposed models in this dissertation can be further extended to more extensive studies of CREB-dependent signal transduction networks.