Luận án Tiến sĩ: Nghiên cứu xây dựng hệ thống kích thích tế bào thần kinh và ứng dụng trong đánh giá đáp ứng không gian của tế bào vị trí hồi Hải mã

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENCE ACADEMY OF MILITARY SCIENCE AND TECHNOLOGY TA QUOC GIAP RESEARCH ON ESTABLISHING THE NEURAL STIMULATION SYSTEM AND APPLY FOR EVALUATING THE SPATIAL RESPONSE OF HIPPOCAMPAL PLACE CELLS DOCTOR OF ENGINEERING DISSERTATION HANOI - 2020 MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENCE ACADEMY OF MILITARY SCIENCE AND TECHNOLOGY TA QUOC GIAP RESEARCH ON ESTABLISHING THE NEURAL STIMULATION SYSTEM AND APPLY FOR EVALUATING THE SPATIAL RESPONSE OF HIPPOCAMPAL PLACE CELLS Specialization: Electronic engineering Code: 52 02 03 DOCTOR OF ENGINEERING DISSERTATION SUPERVISORS: Dr NGUYEN LE CHIEN Dr LE KY BIEN HA NOI - 2020 i DECLARATION I hereby declare that this dissertation is my original work The data and results presented in the dissertation are honest and have not been published in any other work References are fully cited 10th January, 2020 giả luận án TA Quoc Giap ii ACKNOWLEDGMENTS First and foremost, I would like to express my deep appreciation to my direct supervisors, Dr NGUYEN Le Chien, Dr LE Ky Bien and Association Professor TRAN Hai Anh, who enthusiastically guided me during my whole PhD time Thank you very much for many meaningful advices and discussion for my work I learnt from the mentors not only techniques for fulfilling my PhD work, but also methods for solving problems in a lab as well as in the life Thank you very much for revising my thesis, giving me helpful comments and advices My sincere appreciations must go to other teachers in the Departments for their encouragement, knowledge sharing, supports and helps in our course and conduct the thesis I would like to express my sincere thanks to the Institute of Electronics – Academy of Military Science and Technology; Department of Physiology, Department of Material Equipment – VietNam Military Medical University, where I study, live and work for creating favorable conditions for me to participate in studying and researching during my time as a PhD student I want to express my special thank to the leader of Academy of Military science and technology and other collaborator centers for their support and help for this work Finally, I would like to thank my family members for their love, encouragement And especially, I would thank my wife who have sacrificed a lot of things for supporting me to fulfill my PhD work iii TABLE OF CONTENTS Page LIST OF SYMBOL AND ABBREVIATION……………………………… v LIST OF FIGURES AND TABLES…………………………………………ix INTRODUCTION CHAPTER OVERVIEW ABOUT ELECTRICAL ACTIVITY OF NEURONS 1.1 Membrane potential of neurons 1.1.1 Structure of nerve cells membrane 1.1.2 Resting and action potential 1.2 Electrical nerve stimulation and medical significance 12 1.3 The response of cell membranes to electrical stimulation 16 1.4 The recording methods of the neuronal action potential 18 1.5 Hippocampus and hippocampal place cells 21 1.5.1 Structural characteristics 21 1.5.2 Function of the Hippocampus 21 1.6 Fundamentals of electronic circuit model of neuron 23 1.7 Related research to this dissertation 26 1.8 Chapter conclusion 29 CHAPTER EQUIVALENT ELECTRICAL CIRCUIT MODEL AND NEURONAL ELECTRICAL STIMULATION ALGORITHMS 31 2.1 Electronic model of neuron membrane and assessment of electric stimulation parameters 32 2.1.1 Electronic circuit model of neurons 32 2.1.2 Simulation of stimulating parameters on Maeda and Makino models 34 2.1.3 Simulation results and discussion 36 2.2 The system for stimulation and recording the electrical activity of neurons 39 2.3 Building electrical stimulation algorithm model for neurons 41 iv 2.3.1 Model and algorithm of electrical stimulation of neurons with NPT test 41 2.3.2 Model and algorithm of electrical stimulation of neurons with spatial response tests 47 2.4 Chapter conclusion 63 CHAPTER EVALUATING THE STIMULATION ALGORITHMS AND THE SYSTEM BY BEHAVIOURAL RESPONSES AND PRACTICAL EXERCISES ON MICE 64 3.1 Materials and methods 64 3.2 Simulation results 67 3.2.1 Simulation of the NPT task 68 3.2.2 Response simulation in spatial exercises 69 3.3 Analyze and evaluate experimental results on mice 74 3.3.1 Experimental results performed on NPT test 74 3.3.2 Experimental results performed on the spatial response tests 79 3.4 The results of stimulating and recording experiments of the neuronal electronic activity in the hippocampus on mice………………………………80 3.4.1 Unit isolation and recording……………………………………… 80 3.4.2 Common characteristics of hippocampal place cells……………… 82 3.5 The evaluation of the algorithms, stimulation and recording systems for the electrical activity of neurons…………………………………………………83 3.5.1 The evaluation of algorithms……………………………………… 83 3.5.2 The evaluation of stimulating and recording system for the electrical activity of neurons 86 3.6 Chapter conclusion 94 REFERENCES 100 APPENDICES ………………………………………………………………… v LIST OF SYMBOLS AND ABBREVIATIONS 𝐶 Ions concentration 𝐶𝑚 Capacitance of the membrane per unit plane cr The adjusted response number countInterVal Number of stops to adjust the parameter delayTime The minimum time from when the mouse receives the reward until the new reward area appears deltaTime The time it takes to count from the time the mouse receives the prize until the new reward area appears delta Limits the distance the mouse moves to get the reward 𝑑𝐷𝑀𝑇 The distance the mouse moves over a certain period of time in the DMT test 𝑑𝑅𝑅𝑃𝑆𝑇 The distance the mouse moves over a certain period of time in the RRPST test 𝑑𝑃𝐿𝑇 The distance the mouse moves over a certain period of time in the PLT test 𝑑𝑋 Diameter on the horizontal axis of the virtual environment 𝑑𝑌 Diameter on the vertical axis of the virtual environment 𝐸𝐴 Action potential of cell 𝐸𝐾 Resting potential of cell 𝐸̅ Electric field strength 𝐹 Faraday constant 𝑔𝑁𝑎 Conductivity of Na+ ion channels 𝑔𝐾 Conductivity of K+ ion channels 𝑔𝐿 Conductivity of secondary ion channels Interval Interval to stop for parameter adjustment 𝐼𝑖 Intra-axonal current vi 𝐼𝑘𝑡 Cell membrane stimulated current 𝐼𝑜 Extra-axonal current 𝐼𝑠 Stimulation current per unit of time K IN Intracellular K+ concentration K OUT Extracellular K+ concentration maxT The maximum time of task maxPt The maximum number of rewards maxwidth Radius of mice area moving M50 50 percent of the optimal M70 70 percent of the optimal M80 80 percent of the optimal n Valence of ions Na Na OUT Extracellular Na+ concentration IN Intracellular Na+ concentration 𝑅 Constant 𝑅𝑚 Membrane resistance per unit area 𝑇 Absolute temperature 𝑡 Time to stimulate 𝑡1 Rewarding eligible time 𝑡2 Reward receiving time 𝑡𝐿𝑇 Total amount of exercise time for the mouse 𝑡𝑆 Training time (also the total time of sessions) 𝑡𝐼𝑛 Rest time to adjust the value of the stimulating parameter 𝑉𝑚 Membrane potential Pt Number of rewards 𝑉𝑚 – 𝑉𝑁𝑎 Transmembrane potential of Na+ channel vii 𝑉𝑚 – 𝑉𝐾 Transmembrane potential of K+ channel 𝑉𝑚 – 𝑉𝐿 Transmembrane potential of secondary channels 𝑉′ Electric membrane charge 𝑣𝑚 ̅̅̅̅ The mean of movement speed of the mouse in the open environment 𝑋𝑚𝑎𝑥 Maximum diameter in the horizontal axis of the virtual environment 𝑋𝑚𝑖𝑛 Minimum diameter in the horizontal axis of the virtual environment x0, y0 Reward coordinates of mouse before t xs, ys The coordinates of the mice at the time t is assigned with x0, y0 which is the original position of the mice xt ,yt Reward coordinates of mouse at 𝑡 xz1, yz1 The x and y coordinates of the center of the reward area xz2, yz2 The x and y coordinates of the center of the reward area xzt, yzt x, y coordinates of the center of the current reward area 𝑌𝑚𝑎𝑥 Maximum diameter in the vertical axis of the virtual environment 𝑌𝑚𝑖𝑛 Minimum diameter in the vertical axis of the virtual environment 𝑧1 Reward region 𝑧2 Reward region wz Radius of the reward area 𝛥𝑡 System latency 𝛥𝑡𝐷𝑀𝑇 System latency in DMT test 𝛥𝑡𝑁𝑃𝑇 System latency in NPT test 𝛥𝑡𝑅𝑅𝑃𝑆𝑇 System latency in RRPST test viii 𝛥𝑡𝑃𝐿𝑇 System latency in PLT test 𝜙𝑖 Inner membrane potential 𝜙0 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BACHD-Tg5 Rat Model of Huntington’s Disease”, Cereb Cortex, doi: 10.1093/cercor/bhz009 [Epub ahead of print] 111 APPENDICES Table The results of nose – poking response depend on intensity Intensity (µA) 20 30 40 50 60 70 80 90 100 110 120 130 140 Mice’name Day Ctr07 14 49 95 95 127 120 159 160 136 151 150 Ctr14 14 84 94 144 120 107 158 125 113 77 113 34 Ctr16 12 11 87 135 107 93 181 200 202 204 154 194 Ctr21 10 48 66 66 107 135 115 127 162 174 39 Ctr22 11 21 167 70 165 197 177 194 225 Ctr25 23 52 72 100 70 119 161 61 58 19 24 75 Day Ctr07 20 11 22 95 129 89 143 128 118 128 173 Ctr14 42 114 138 111 121 116 111 146 121 123 127 166 Ctr16 11 105 143 162 201 177 196 204 173 178 164 Ctr21 16 17 76 65 120 165 158 189 160 186 147 135 166 Ctr22 2 87 110 118 195 185 215 186 176 190 164 Ctr25 15 83 41 148 109 134 87 124 60 68 34 74 X 10 12 38 66 100 104 138 139 151 145 132 134 135 ±SE 11 11 13 11 10 12 12 14 15 15 17 112 Table The results of nose – poking response depend on frequency Frequency (Hz) 16 20 25 32 40 50 63 80 100 126 158 Mice’name Day Ctr027 12 31 18 29 58 48 123 144 145 110 146 Ctr029 15 5 25 10 29 233 165 184 191 253 Ctr030 19 12 24 27 82 92 158 211 191 169 192 Ctr032 19 12 16 74 168 161 145 155 143 Ctr033 18 17 27 62 93 128 112 151 74 Ctr034 12 32 20 19 23 117 147 204 195 214 179 Ctr006 24 62 103 101 191 250 190 222 240 250 181 Day Ctr027 16 17 10 34 52 53 99 132 144 133 95 Ctr029 10 32 59 219 228 259 258 271 Ctr030 24 20 62 77 159 152 189 154 130 Ctr032 13 15 30 11 41 115 202 190 183 176 179 Ctr033 13 73 115 108 146 138 135 81 Ctr034 24 13 29 167 178 187 188 202 157 Ctr006 22 31 106 111 215 262 245 212 226 235 185 X 13 13 28 29 72 121 173 178 185 185 127 ±SE 16 19 13 11 12 15 113 Table The results of system latency time in NPT test (unit: s) Turn Turn Turn Turn Turn Turn Turn Turn Turn Turn 10 0.03 0.10 0.07 0.05 0.09 0.04 0.09 0.10 0.04 0.02 0.07 0.05 0.05 0.04 0.02 0.11 0.09 0.03 0.04 0.01 0.02 0.09 0.07 0.07 0.02 0.01 0.09 0.10 0.08 0.05 0.05 0.09 0.02 0.05 0.08 0.01 0.02 0.07 0.03 0.15 0.06 0.06 0.09 0.09 0.07 0.04 0.08 0.05 0.06 0.06 0.08 0.07 0.05 0.10 0.08 0.09 0.04 0.09 0.05 0.02 0.08 0.03 0.04 0.10 0.01 0.04 0.00 0.04 0.11 0.08 0.10 0.02 0.04 0.04 0.09 0.04 0.01 0.10 0.07 0.09 0.10 0.04 0.10 0.10 0.04 0.07 0.07 0.06 0.05 0.09 0.01 0.02 0.11 0.10 0.01 0.05 0.08 0.10 0.06 0.04 XNPT = 0,06 SD = 0,03 tNPT.Max = 0,15 tNPT.Min = 0,01 114 Table The results of system latency time in DMT test (unit: ms) Turn Turn Turn Turn Turn Turn Turn Turn Turn Turn 10 3.72 3.91 4.23 7.55 1.63 7.67 5.86 7.69 6.80 5.87 3.16 4.22 3.41 3.14 3.10 4.18 10.09 6.11 6.02 3.13 6.06 5.22 6.15 5.16 2.08 5.18 5.21 8.07 6.13 4.71 3.13 4.22 6.17 4.97 2.05 3.11 5.18 8.81 2.08 5.21 2.09 3.09 4.17 4.23 5.12 6.12 4.16 6.14 5.21 5.11 8.94 6.13 4.21 4.10 2.23 4.24 3.14 3.19 5.98 6.14 5.18 3.09 3.06 3.13 4.23 3.15 5.10 5.22 7.52 3.01 6.14 3.16 6.12 2.06 4.16 7.64 4.24 9.77 3.12 8.49 5.81 3.14 10.47 4.30 2.84 5.52 3.20 5.16 0.71 5.18 2.10 6.42 3.12 5.08 4.15 5.98 5.23 2.10 3.25 10.34 6.12 2.06 5.63 3.16 3.17 7.78 6.12 3.18 7.21 2.72 6.12 4.21 7.19 10.63 5.16 3.16 3.02 5.25 3.15 5.21 3.13 4.82 6.71 2.06 4.23 5.86 3.19 6.06 6.05 4.18 4.79 3.12 3.19 4.17 4.14 5.13 8.83 5.19 1.54 7.20 3.18 3.17 6.20 3.13 3.18 4.79 3.09 5.16 5.23 4.22 3.10 4.23 5.15 6.14 4.37 4.17 6.13 3.17 3.11 4.15 4.23 5.15 4.93 3.12 10.07 10.10 5.65 3.17 5.97 3.20 10.15 3.10 8.17 5.10 3.16 6.21 3.12 4.16 4.35 5.21 5.13 6.14 5.14 5.18 1.94 3.12 3.16 3.11 3.19 4.16 5.26 6.05 5.22 5.26 3.15 4.13 6.17 5.20 5.10 6.57 6.15 5.19 6.01 5.41 5.22 2.05 5.13 4.22 4.17 4.17 3.15 5.59 1.43 5.10 4.20 5.23 4.19 7.11 4.20 3.18 6.10 2.06 2.97 4.15 2.09 5.16 4.12 2.81 2.07 5.31 5.13 3.11 6.08 5.19 4.45 7.88 7.53 7.04 3.16 5.07 4.20 2.40 3.11 3.08 4.18 3.16 7.21 3.17 4.14 4.20 4.13 5.14 3.15 3.12 5.13 6.03 5.22 3.08 3.12 5.14 5.13 5.22 6.21 3.15 3.16 3.15 8.67 3.09 5.22 5.18 8.26 8.57 5.23 9.09 3.07 8.72 4.03 1.96 6.12 2.05 5.23 6.10 4.17 6.25 3.01 6.14 3.23 6.12 4.12 3.09 3.12 6.86 2.05 6.18 5.17 4.18 6.85 2.09 5.17 6.13 4.19 3.09 4.10 3.09 4.18 6.14 3.07 4.23 1.89 3.11 6.15 3.17 8.71 5.11 5.40 3.05 3.15 6.11 5.22 4.17 5.21 9.74 3.10 5.25 5.16 8.95 4.16 4.18 6.13 2.07 115 3.11 5.19 6.13 3.00 5.16 10.80 8.80 10.62 10.84 5.13 9.56 4.25 6.07 3.11 8.16 2.06 4.11 3.10 5.17 5.19 4.16 6.13 5.18 4.20 6.12 5.21 6.14 5.20 3.00 3.16 7.90 6.14 4.68 5.16 5.22 6.20 4.25 8.31 5.17 3.15 4.17 2.89 5.38 2.08 6.14 2.98 4.26 4.18 4.16 5.19 5.23 5.12 6.35 3.16 6.18 4.26 3.09 8.31 4.22 4.55 3.09 10.81 4.10 4.14 8.13 6.13 8.84 10.61 4.17 7.19 2.05 10.58 3.29 3.03 2.51 5.16 6.10 3.08 3.10 4.09 3.12 9.87 3.15 4.05 5.85 4.18 2.06 3.12 2.00 3.05 5.25 3.09 5.16 5.20 6.16 5.09 6.06 8.77 5.06 6.10 8.82 6.12 2.03 4.23 11.64 7.84 5.27 6.16 4.24 3.08 4.18 6.14 5.06 4.14 6.17 6.20 6.20 3.11 3.10 8.77 5.12 10.88 5.11 3.07 2.95 8.46 3.09 4.23 11.12 5.91 2.04 4.14 3.07 5.25 4.14 7.06 6.20 6.16 3.13 2.01 3.08 4.10 4.03 3.04 5.14 1.46 6.15 2.04 3.09 4.16 2.93 6.12 5.10 3.07 5.21 3.03 11.27 6.15 2.08 1.19 3.29 6.21 4.97 4.83 6.21 4.05 6.16 4.06 6.10 3.08 XDMT = 4,88 SD = 2,01 tDMT.Max = 11,64 tDMT.Min = 0,71 116 Table The results of system latency time in RRPST test (unit: ms) Turn Turn Turn Turn Turn Turn Turn Turn Turn Turn 10 4.00 6.45 5.36 3.32 2.81 5.24 5.83 2.96 4.03 6.79 3.12 5.45 2.09 3.21 1.13 6.12 5.17 9.72 4.09 4.20 2.12 3.11 1.96 5.35 5.14 6.06 5.02 5.09 5.22 4.38 2.11 2.52 3.14 3.18 3.09 2.05 5.17 3.04 4.09 3.23 4.16 5.68 4.18 2.03 5.16 5.06 6.03 5.14 3.16 3.05 4.13 3.04 5.01 6.13 8.52 5.17 6.18 4.24 9.37 3.18 5.02 5.07 3.10 4.15 2.00 2.10 4.14 4.17 4.26 4.15 3.15 4.22 5.13 4.13 5.13 5.07 6.11 6.14 7.63 0.77 6.05 4.06 9.68 6.18 3.13 3.08 2.13 4.13 5.16 3.07 5.18 6.13 5.05 3.08 6.15 3.06 4.17 4.13 2.01 4.23 6.08 5.04 6.27 2.56 4.13 6.51 3.13 7.81 4.20 6.07 6.25 5.07 9.27 4.08 5.21 6.06 5.07 4.17 6.12 6.11 8.02 5.87 3.17 5.23 4.13 5.20 5.17 5.08 1.97 8.02 2.00 4.24 3.04 3.09 4.22 4.06 5.04 6.19 6.15 2.12 6.13 3.02 6.17 6.81 6.12 5.37 5.24 2.05 5.16 3.09 5.83 6.16 4.14 5.14 2.08 4.10 3.11 4.18 4.22 4.18 6.12 8.85 3.80 5.49 8.42 2.06 3.72 1.98 5.16 3.12 6.05 4.18 4.19 5.34 4.17 4.13 4.26 0.00 6.14 3.04 0.54 3.05 6.98 2.09 6.16 1.96 8.33 4.18 4.24 4.23 3.19 6.79 0.00 3.32 6.09 3.90 5.30 0.00 4.12 5.06 5.12 5.11 3.10 4.35 6.00 1.97 5.14 6.13 3.15 6.13 6.11 4.15 5.12 3.13 4.13 2.10 3.15 3.13 6.29 4.03 3.20 3.02 1.62 4.09 4.07 5.12 2.02 5.13 6.17 2.05 5.16 3.13 5.23 4.17 7.00 2.06 2.10 6.15 4.09 6.04 4.19 4.16 4.07 4.11 3.14 6.13 4.13 3.12 5.16 4.16 8.44 3.19 4.16 6.13 5.14 3.20 3.20 4.13 4.26 4.16 3.20 5.15 3.09 5.03 3.18 5.05 8.75 3.12 3.05 6.07 2.07 2.11 4.11 6.17 4.13 3.12 2.11 0.00 3.16 3.18 2.09 5.79 1.58 6.10 3.05 6.03 4.07 6.11 2.02 6.08 4.13 3.17 4.16 3.22 3.14 6.18 4.15 3.12 4.17 4.35 11.23 6.05 5.12 7.83 5.12 5.03 5.12 0.00 2.09 4.15 2.07 4.23 4.24 4.19 3.19 2.06 5.58 4.25 4.14 3.02 5.18 9.48 8.20 2.00 3.10 5.05 3.13 6.13 5.38 5.79 117 5.15 3.03 7.40 7.15 6.17 6.14 4.09 4.14 4.25 3.07 8.86 4.26 6.03 3.54 6.11 6.09 3.14 6.18 3.14 3.11 3.10 1.94 5.21 2.11 3.13 5.17 5.06 4.15 8.36 3.07 5.13 6.17 6.02 1.97 4.09 3.13 5.20 3.37 2.05 4.10 3.15 4.07 5.13 4.21 5.14 5.14 6.04 3.19 9.95 5.14 4.18 6.13 3.02 5.08 5.39 2.98 2.28 2.28 7.19 3.44 3.18 4.08 4.21 6.44 2.10 4.17 11.16 0.00 4.08 8.79 4.16 5.17 5.12 5.11 5.20 5.13 5.21 5.27 6.25 3.11 5.13 4.14 5.20 2.10 7.09 6.47 6.86 0.00 6.62 4.06 6.17 5.20 3.07 5.16 3.09 4.18 3.43 2.05 8.87 5.11 5.19 3.10 3.34 7.70 3.12 0.50 3.13 0.00 5.20 6.33 2.07 5.21 6.14 5.12 5.08 4.23 5.06 0.00 5.07 4.16 6.20 5.10 4.44 4.11 5.08 4.14 4.14 0.00 6.08 6.04 4.18 3.10 3.18 3.05 5.87 6.12 2.11 0.00 5.34 3.16 4.08 3.04 4.03 3.11 3.08 5.13 4.40 0.00 5.98 5.06 5.22 3.09 3.17 3.04 4.06 7.21 5.20 5.16 5.17 5.34 6.25 5.04 4.01 6.79 4.06 5.09 5.09 3.09 4.01 2.03 XRRPST = 4,44 SD = 1,81 tRRPST.Max = 11,23 tRRPST.Min = 0,00 118 Table The results of system latency time in PLT test (unit: ms) Turn Turn Turn Turn Turn Turn Turn Turn Turn Turn 10 5.16 3.19 7.61 11.69 3.14 7.03 8.74 5.15 6.37 4.01 8.24 10.35 6.36 9.83 4.13 6.87 3.09 5.13 9.63 4.41 3.07 3.16 2.08 6.23 4.05 2.08 2.05 5.05 5.03 5.23 5.15 3.13 4.15 6.17 4.13 1.99 7.97 5.22 2.08 1.99 3.18 3.11 3.07 2.01 3.12 5.19 5.06 5.19 5.41 4.17 5.04 5.05 4.15 7.19 5.07 3.11 3.13 6.76 7.03 3.08 7.74 4.13 3.16 5.10 6.10 3.04 6.15 5.58 5.36 6.10 3.23 6.07 3.05 3.15 5.10 6.15 5.09 5.22 6.23 2.08 6.20 10.41 6.16 5.02 5.12 4.41 4.18 4.12 2.01 4.12 4.12 3.11 5.16 7.77 6.17 5.14 2.10 3.16 4.47 2.09 6.15 6.14 4.13 4.22 3.07 3.17 3.02 2.09 5.16 5.15 5.08 5.22 4.23 3.11 3.13 4.12 4.64 3.05 4.13 6.11 5.20 3.03 11.13 4.13 3.11 3.12 9.36 6.12 5.15 6.45 10.22 5.22 5.06 6.18 3.11 4.16 4.10 5.13 5.19 4.23 8.58 3.45 5.19 3.07 3.11 3.12 4.22 3.20 5.12 6.46 4.17 4.13 5.54 4.24 4.05 9.27 4.15 4.17 3.50 4.17 5.11 4.14 3.11 6.34 2.07 3.55 5.38 9.65 4.28 3.04 3.15 3.12 4.23 3.15 6.14 1.97 2.11 5.08 3.19 5.15 7.44 5.17 4.14 6.07 5.19 3.10 3.21 6.70 4.07 3.24 6.04 6.13 6.07 5.15 8.75 6.12 6.03 4.17 2.12 5.10 4.18 5.09 4.17 8.40 4.03 6.16 10.11 6.27 3.21 5.51 7.75 6.15 6.12 7.12 9.65 3.11 4.12 4.22 5.13 5.09 6.06 6.00 4.16 3.19 5.06 3.12 4.08 6.13 5.24 3.14 3.15 6.29 6.16 3.96 5.17 3.12 5.13 3.06 2.18 3.14 3.18 5.22 1.77 4.16 2.00 3.12 6.16 3.22 4.18 3.22 4.05 4.14 4.14 3.05 2.17 3.12 3.18 4.10 3.03 3.21 5.92 3.24 3.16 5.17 5.16 6.15 7.52 4.17 3.40 2.25 6.05 6.12 7.00 3.05 5.07 4.15 4.67 1.99 4.93 5.21 6.12 4.08 4.16 3.10 5.21 3.25 3.12 2.08 4.02 5.13 3.19 5.20 2.10 5.06 9.73 5.21 5.07 2.02 3.15 3.07 4.22 1.86 3.82 3.11 1.20 5.13 7.90 6.31 6.86 7.72 1.98 3.04 5.20 6.10 4.15 3.13 10.35 5.19 4.21 3.61 5.20 2.08 4.18 4.13 10.15 4.49 5.06 3.11 4.03 3.22 119 5.09 5.18 6.06 3.05 5.12 5.19 6.17 7.51 4.84 8.64 2.49 6.10 5.15 3.12 6.04 4.24 5.21 6.06 2.29 6.15 5.07 5.18 3.10 6.04 4.24 4.13 8.77 6.13 4.21 5.15 2.08 4.19 5.24 3.12 6.06 4.15 5.08 7.59 4.08 24.28 6.11 5.07 3.13 5.12 5.16 2.31 6.84 3.14 2.07 4.25 5.08 6.17 10.62 3.19 8.70 5.96 10.81 3.05 2.11 3.09 6.17 9.86 6.05 6.02 4.17 6.11 4.24 4.15 4.07 5.20 5.22 6.92 3.22 5.20 5.07 3.00 5.22 2.09 4.16 5.20 3.15 7.49 8.33 6.07 2.11 2.13 2.01 3.11 5.21 5.10 11.07 8.63 6.53 5.17 6.04 6.60 4.15 2.05 6.08 4.14 9.94 5.02 4.87 4.06 10.77 3.01 6.62 3.04 8.51 8.55 4.09 5.17 5.22 4.16 2.02 3.38 5.09 4.16 8.20 1.99 3.15 10.04 5.14 10.34 5.12 8.03 3.21 7.07 3.09 6.17 6.12 5.12 6.12 6.15 6.05 4.07 2.08 5.15 6.37 5.21 4.06 5.24 5.18 4.12 6.09 7.23 3.04 5.08 6.85 5.14 5.21 5.17 3.14 7.60 4.03 4.14 2.11 6.24 5.12 3.04 3.05 6.81 1.99 5.13 5.16 3.07 4.13 5.05 6.90 3.08 XPLT = 4,91 SD = 2,12 tPLT.Max = 24,28 tPLT.Min = 1,20 ... and have not been published in any other work References are fully cited 10th January, 2020 giả luận án TA Quoc Giap ii ACKNOWLEDGMENTS First and foremost, I would like to express my deep appreciation... does not exceed the threshold, the response is not propagated (electric tone) If the response is strong enough, a nerve impulse (action potential impulse) will be produced according to the "all... electrical impulse and duration of stimulation? Can the membrane voltage be reached by a short, strong stimulus or a long, weak stimulus? The curve illustrates the relationship between intensity