Faculteit Farmaceutische, Biomedische en Diergeneeskundige Wetenschappen Departement Biomedische Wetenschappen Dynamics of neuronal responses in silico and in vitro De dynamische respons van neuronen in silico en in vitro Proefschrift voorgelegd tot het behalen van de graad van doctor in de biomedische wetenschappen aan de universiteit van Antwerpen te verdedigen door Christophe VERBIST Prof. Michele Giugliano, Prof. Alain Labro Antwerpen, 2020 2 Table of contents 3 Abbreviations .................................................................................................. 9 Samenvatting................................................................................................. 11 Summary ....................................................................................................... 17 CHAPTER 1: Introduction ........................................................................... 21 1.1 The Axon Initial Segment ............................................................... 24 1.2 Theories about the “temporal sharpness” of AP generation ........... 27 1.2.1 Cooperative Sodium channels ............................................... 28 1.2.2 Active backpropagation ......................................................... 29 1.2.3 The critical resistive coupling theory .................................... 29 1.3 The morphological location of the AIS .......................................... 30 1.4 The neuronal models of the Blue Brain Project .............................. 31 1.5 NEURON simulator ........................................................................ 34 1.6 The Julia programming language ................................................... 36 1.7 The transfer function of a neuron ................................................... 37 1.8 References ....................................................................................... 43 CHAPTER 2: Research goals ....................................................................... 55 2.1 What are the cellular correlates of IQ? ........................................... 56 2.2 What influences the information capabilities of excitatory neurons? 56 2.3 How do diverse layer 1 inhibitory neurons transfer information? .. 57 CHAPTER 3: Large and fast human pyramidal neurons associate with intelligence .................................................................................................... 59 3.1 Chapter information ........................................................................ 60 3.1.1 Publication ............................................................................. 60 3.1.2 Author contribution ............................................................... 60 Abstract ........................................................................................... 61 Introduction ..................................................................................... 61 Results ............................................................................................. 66 4 3.4.1 IQ scores positively correlate with cortical thickness of the temporal lobe ....................................................................................... 66 3.4.2 IQ scores positively correlate with dendritic structure of temporal cortical pyramidal neurons ................................................... 67 3.4.3 Larger dendrites lead to faster AP onset and improved encoding properties ............................................................................. 69 3.4.4 Higher IQ scores associate with faster Aps ........................... 74 3.5 Discussion ....................................................................................... 78 3.6 Materials and methods .................................................................... 82 3.6.1 Human subjects and brain tissue ........................................... 82 3.6.2 IQ scores ................................................................................ 82 3.6.3 MRI data and cortical thickness estimation .......................... 83 3.6.4 Slice preparation .................................................................... 83 3.6.5 Electrophysiological recordings ............................................ 84 3.6.6 Morphological analysis ......................................................... 84 3.6.7 NEURON modelling ............................................................. 85 3.6.8 Action Potential waveform analysis of electrophysiological recordings ............................................................................................ 87 3.6.9 Statistical analysis ................................................................. 88 3.7 Acknowledgements ......................................................................... 88 3.8 Ethics .............................................................................................. 88 3.9 References ....................................................................................... 90 CHAPTER 4: The location of the axon initial segment affects the bandwidth of spike initiation dynamics .......................................................................... 97 4.1 Chapter information ........................................................................ 98 4.1.1 Publication ............................................................................. 98 4.1.2 Author contribution ............................................................... 98 4.2 Abstract ........................................................................................... 99 4.3 Author summary ............................................................................. 99 4.4 Introduction ................................................................................... 100 4.5 Results ........................................................................................... 101 4.5.1 The AIS location alters neuronal responsiveness ................ 104 5 4.5.2 Multicompartmental neuron models ................................... 106 4.5.3 Network simulations ........................................................... 113 4.6 Discussion ..................................................................................... 119 4.7 Materials and Methods ................................................................. 123 4.7.1 Conductance-based model neurons ..................................... 123 4.7.2 Linear Dynamical Transfer Properties: Spike-Train Analysis in the Fourier Domain ....................................................................... 124 4.7.3 Action Potential Trajectory and Transfer Gain profile ....... 126 4.7.4 Reduction to the Integrate-and-Fire point neuron model .... 126 4.7.5 Liquid State Machine: the classification task ...................... 127 4.8 Data availability ............................................................................ 131 4.9 Acknowledgments ........................................................................ 131 CHAPTER 5: Homogeneous and narrow bandwidth of spike initiation in rat L1 cortical interneurons .............................................................................. 137 5.1 Chapter Information ...................................................................... 138 5.1.1 Publication ........................................................................... 138 5.1.2 Author contribution ............................................................. 138 5.2 Abstract ......................................................................................... 139 5.3 Introduction ................................................................................... 140 5.4 Materials and Methods ................................................................. 142 5.4.1 Brain tissue slice preparation .............................................. 142 5.4.2 Electrophysiology ................................................................ 142 5.4.3 Electrical phenotype identification ...................................... 144 5.4.4 Spike-triggered average and dynamical transfer function ... 146 5.4.5 Rapidness of the action potential at its onset ...................... 148 5.4.6 Computer simulations ......................................................... 149 5.4.7 Statistical analysis ............................................................... 149 5.4.8 Data availability .................................................................. 150 5.5 Results ........................................................................................... 150 5.5.1 Encoding properties of L1 interneurons .............................. 150 5.5.2 Electrical classes and encoding properties .......................... 152 6 5.5.3 Dependency of cutoff on the mean firing rate ..................... 153 5.5.4 Action potential rapidity at onset ........................................ 156 5.5.5 Transfer at high spectral frequencies .................................. 157 5.6 Discussion ..................................................................................... 159 5.7 Acknowledgements ....................................................................... 162 5.8 References ..................................................................................... 163 CHAPTER 6: Conclusion ........................................................................... 169 CHAPTER 7: Scientific curriculum vitae................................................... 175 CHAPTER 8: Acknowledgments ..............................................................