The Book of GENESIS (2^nd Ed., 2nd ed. 1998. Softcover reprint of the original 2nd ed. 1998) Exploring Realistic Neural Models with the GEneral NEural SImulation System

"The Book of GENESIS" is in two parts. Firstly, a collection of contributed articles describes projects created using the GENESIS system, and then a step-by-step tutorial explains how the software works and how best to manipulate it so as to achieve maximum use. As a result, this publication may be seen as a reference guide, a textbook for course use, and as a resource to which readers can turn for ideas on how to devise their own models and applications. The accompanying cross-platform CD-ROM contains the full source code for GENESIS and its graphical interface, XODUS; the GENESIS Reference Manual in hypertext, plain text and Postscript formats; numerous tutorial simulations and example simulation scripts, including all of those used in the book. As a bonus, also included on the CD are a number of items which are not part of the standard distribution of GENESIS. The GENESIS system will continue to be made available through the Cal Tech World Wide Web site, as well, at: www.bbb.caltech.edu/GENESIS.

I Neurobiological Tutorials with GENESIS.- 1 Introduction.- 1.1 Computational Neuroscience.- 1.2 Using This Book.- 2 Compartmental Modeling.- 2.1 Modeling Neurons.- 2.1.1 Detailed Compartmental Models.- 2.1.2 Equivalent Cylinder Models.- 2.1.3 Single and Few Compartment Models.- 2.2 Equivalent Circuit of a Single Compartment.- 2.3 Axonal Connections, Synapses and Networks.- 2.4 Simulation Accuracy.- 2.4.1 Choice of Numerical Integration Technique.- 2.4.2 Integration Time Step.- 2.4.3 Accuracy of GENESIS.- 3 Neural Modeling with GENESIS.- 3.1 What Is GENESIS?.- 3.1.1 Why Use a General Simulator?.- 3.1.2 GENESIS Design Features.- 3.1.3 GENESIS Development.- 3.2 Introduction to the Tutorials.- 3.3 Introduction to the GENESIS Graphical Interface.- 3.3.1 Starting the Simulation.- 3.3.2 The Control Panel.- 3.3.3 Using Help Menus.- 3.3.4 Displaying the Simulation Results.- 4 The Hodgkin—Huxley Model.- 4.1 Introduction.- 4.2 Historical Background.- 4.3 The Mathematical Model.- 4.3.1 Electrical Equivalent Circuit.- 4.3.2 HH Conventions.- 4.3.3 The Ionic Current.- 4.4 Voltage Clamp Experiments.- 4.4.1 Characterizing the K Conductance.- 4.5 GENESIS: Voltage Clamp Experiments.- 4.6 Parameterizing the Rate Constants.- 4.7 Inactivation of the Na Conductance.- 4.8 Current Injection Experiments.- 4.9 Exercises.- 5 Cable and Compartmental Models of Dendritic Trees.- 5.1 Introduction.- 5.2 Background.- 5.2.1 Dendritic Trees: Anatomy, Physiology and Synaptology.- 5.2.2 Summary.- 5.3 The One-Dimensional Cable Equation.- 5.3.1 Basic Concepts and Assumptions.- 5.3.2 The Cable Equation.- 5.4 Solution of the Cable Equation for Several Cases.- 5.4.1 Steady-State Voltage Attenuation with Distance.- 5.4.2 Voltage Decay with Time.- 5.4.3 Functional Significance of ? and ?m.- 5.4.4 The Input Resistance Rin and “Trees Equivalent to a Cylinder”.- 5.4.5 Summary of Main Results from the Cable Equation.- 5.5 Compartmental Modeling Approach.- 5.6 Compartmental Modeling Experiments.- 5.7 Main Insights for Passive Dendrites with Synapses.- 5.8 Biophysics of Excitable Dendrites.- 5.9 Computational Function of Dendrites.- 5.10 Exercises.- 6 Temporal Interactions Between Postsynaptic Potentials.- 6.1 Introduction.- 6.2 Electrical Model of a Patch of Membrane.- 6.2.1 Voltage Response of Passive Membrane to a Current Pulse.- 6.3 Response to Activation of Synaptic Channels.- 6.3.1 The Postsynaptic Current.- 6.3.2 The Postsynaptic Potential.- 6.3.3 Smooth Synaptic Conductance Change: The “Alpha Function”.- 6.4 A Remark on Synaptic Excitation and Inhibition.- 6.5 GENESIS Experiments with PSPs.- 6.5.1 Temporal Summation of Postsynaptic Potentials.- 6.5.2 Nonlinear Summation of Postsynaptic Potentials.- 6.6 Concluding Remarks.- 6.7 Exercises and Projects.- 7 Ion Channels in Bursting Neurons.- 7.1 Introduction.- 7.2 General Properties of Molluscan Neurons.- 7.3 Ionic Conductances — The Dance of the Ions.- 7.3.1 Action Potential Related Conductances.- 7.3.2 Control of Bursting Properties.- 7.4 A Model Molluscan Neuron.- 7.4.1 Adrift in Parameter Space.- 7.4.2 Implementation of the Model.- 7.4.3 Modeling the Channels.- 7.5 The Molluscan Neuron Simulation.- 7.5.1 Using Neurokit.- 7.5.2 Understanding the Results.- 7.6 The Traub Model CA3 Pyramidal Cell.- 7.6.1 Experiments with the Traub Model.- 7.6.2 Firing Patterns.- 7.7 Exercises.- 8 Central Pattern Generators.- 8.1 Introduction.- 8.2 Two-Neuron Oscillators.- 8.2.1 Phase Equation Model of Coupled Oscillators.- 8.2.2 Simulation Parameters.- 8.2.3 Initial Conditions.- 8.2.4 Synaptic Coupling.- 8.2.5 Non-Phase Equation Models.- 8.3 Four-Neuron Oscillators.- 8.3.1 Chains of Coupled Oscillators.- 8.3.2 Simulation Parameters.- 8.3.3 Modeling Gaits.- 8.4 Summary.- 8.5 Exercises.- 9 Dynamics of Cerebral Cortical Networks.- 9.1 Introduction.- 9.2 Piriform Cortex.- 9.3 Structure of the Model.- 9.3.1 Cellular Complexity.- 9.3.2 Network Circuitry.- 9.4 Electroencephalography.- 9.5 Using the Tutorial.- 9.5.1 Getting Started.- 9.5.2 Generating Simulated Data.- 9.5.3 Initial Look at Simulated Activity.- 9.5.4 Observing Network Behavior.- 9.5.5 Varying Network Parameters.- 9.6 Detailed Examination of Network Behavior.- 9.7 Summary.- 9.8 Exercises.- 10 The Network Within: Signaling Pathways.- 10.1 Introduction.- 10.1.1 Nomenclature.- 10.1.2 A Short Short Course in Biochemistry.- 10.1.3 Common Signaling Pathways.- 10.2 Modeling Signaling Pathways.- 10.2.1 Theory.- 10.2.2 Sources of Data.- 10.2.3 Figuring Out the Mechanisms.- 10.2.4 Reaction Rate Constants.- 10.2.5 Enzyme Rate Constants.- 10.2.6 Initial Concentrations.- 10.2.7 Refining the Model.- 10.3 Building Kinetics Models with GENESIS and Kinetikit.- 10.3.1 The kinetics Library.- 10.3.2 Kinetikit.- 10.3.3 A Feedback Model.- 10.3.4 Beyond Kinetikit.- 10.3.5 Connecting Kinetic Models to the Rest of GENESIS.- 10.4 Summary: Molecular Computation.- 10.5 Exercises.- II Creating Simulations with GENESIS.- 11 Constructing New Models.- 11.1 Structurally Realistic Modeling.- 11.2 The Modeling Process.- 11.2.1 Single Neurons or Networks.- 11.2.2 Modeling Steps.- 12 Introduction to GENESIS Programming.- 12.1 Simulating a Simple Compartment.- 12.2 Getting Started with GENESIS.- 12.3 GENESIS Objects and Elements.- 12.3.1 Creating and Deleting Elements.- 12.3.2 Examining and Modifying Elements.- 12.4 Running a GENESIS Simulation.- 12.4.1 Adding Graphics.- 12.4.2 Linking Elements with Messages.- 12.4.3 Adding Buttons to a Form.- 12.5 How GENESIS Performs a Simulation.- 12.6 Exercises.- 13 Simulating a Neuron Soma.- 13.1 Some GENESIS Script Language Conventions.- 13.1.1 Defining Functions in GENESIS.- 13.2 Making a More Realistic Soma Compartment.- 13.2.1 Some Remarks on Units.- 13.2.2 Building a “Squid-Like” Soma.- 13.2.3 GIGO (Garbage In, Garbage Out).- 13.3 Debugging GENESIS Scripts.- 13.4 Exercises.- 14 Adding Voltage-Activated Channels.- 14.1 Review.- 14.2 More Fun With XODUS.- 14.3 Voltage-Activated Channel Objects.- 14.3.1 The hh_channel Object.- 14.3.2 Adding Hodgkin—Huxley Na and K Channels to the Soma.- 14.4 Final Additions and Improvements.- 14.4.1 Use of the Compartment initVm Field.- 14.4.2 Overlaying GENESIS Plots.- 14.5 Extended Objects.- 14.6 Exercises.- 15 Adding Dendrites and Synapses.- 15.1 Adding a Dendrite Compartment.- 15.2 Providing Synaptic Input.- 15.3 Connections Between Neurons.- 15.4 Learning and Synaptic Plasticity.- 15.4.1 Continous Modification of the Synaptic Weight.- 15.4.2 Use of the MOD Message.- 15.4.3 Hebbian Learning with the hebbsynchan.- 15.4.4 Customizing the synchan or hebbsynchan.- 15.5 Where Do We Go from Here?.- 15.6 Exercises.- 16 Automating Cell Construction with the Cell Reader.- 16.1 Introduction.- 16.2 Creating a Library of Prototype Elements.- 16.2.1 Future Changes in the Cell Reader.- 16.2.2 The protodefs.g Script.- 16.3 The Format of the Cell Descriptor File.- 16.4 Modifying the Main Script to Use the Cell Reader.- 16.5 The Neurokit Simulation.- 16.6 Exercises.- 17 Building a Cell with Neurokit.- 17.1 Introduction and Review.- 17.2 Customizing the userprefs File.- 17.2.1 Step 1.- 17.2.2 Step 2.- 17.2.3 Step 3.- 17.3 The Cell Descriptor File.- 17.4 Some Experiments Using Neurokit.- 17.5 Exercises and Projects.- 18 Constructing Neural Circuits and Networks.- 18.1 Introduction.- 18.2 The Orient_tut Simulation.- 18.3 Running the Simulation.- 18.4 Creating a Network Simulation.- 18.5 Defining Prototypes.- 18.6 Creating Arrays of Cells.- 18.7 Making Synaptic Connections.- 18.7.1 Specifying Individual Synaptic Connections.- 18.7.2 Commands Involving Groups of Synapses.- 18.7.3 Utility Functions for Synapses.- 18.8 Setting Up the Inputs.- 18.9 Summary.- 18.10 Exercises.- 19 Implementing Other Types of Channels.- 19.1 Introduction.- 19.2 Using Experimental Data to Make a tabchannel.- 19.2.1 Setting the tabchannel Internal Fields.- 19.2.2 Testing and Editing the Channel.- 19.3 Using Equations for the Rate Constants.- 19.4 Implementing Calcium-Dependent Conductances.- 19.4.1 Calculating the Calcium Concentration.- 19.4.2 The AHP Current.- 19.4.3 The C-Current.- 19.4.4 Other Uses of the table Object.- 19.4.5 The vdep_gate Object.- 19.4.6 Using the tab2Dchannel Object.- 19.5 NMDA Channels.- 19.6 Gap Junctions.- 19.7 Dendrodendritic Synapses.- 19.8 Exercises.- 20 Speeding Up GENESIS Simulations.- 20.1 Introduction.- 20.2 Some General Hints.- 20.3 Numerical Methods Used in GENESIS.- 20.3.1 The Differential Equations Used in GENESIS.- 20.3.2 Explicit Methods.- 20.3.3 Implicit Methods.- 20.3.4 Instability and Stiffness.- 20.3.5 Implementation of the Implicit Methods.- 20.4 The setmethod Command.- 20.5 Using the hsolve Object.- 20.5.1 Modes of Operation.- 20.5.2 Rules for Table Dimensions.- 20.6 Setting up hsolve.- 20.6.1 The findsolvefield Function.- 20.6.2 The DUPLICATE Action.- 20.7 Experiments with the hsolve Object.- 20.8 Exercises.- 21 Large-Scale Simulation Using Parallel GENESIS.- 21.1 Introduction.- 21.2 Classes of Parallel Platforms.- 21.3 Parallel Script Development.- 21.4 Script Language Programming Model.- 21.4.1 Parallel Virtual Machine.- 21.4.2 Namespace.- 21.4.3 Execution (Threads and Synchronization).- 21.4.4 Simulation and Scheduling.- 21.4.5 Node-Specific Script Processing.- 21.4.6 Asynchronous Simulation.- 21.4.7 Zones and Node Identifiers.- 21.4.8 Remote Function Call.- 21.4.9 Asynchronous Remote Function Call.- 21.4.10 Message Creation.- 21.5 Running PGENESIS.- 21.5.1 The pgenesis Startup Script.- 21.5.2 Debug Modes.- 21.6 Network Model Example.- 21.6.1 Setup.- 21.6.2 Simulation Control.- 21.6.3 Lookahead.- 21.7 Parameter Search Examples.- 21.8 I/O Issues.- 21.9 Summary of Script Language Extensions.- 21.9.1 Startup/Shutdown.- 21.9.2 Adding Messages.- 21.9.3 Synaptic Connections.- 21.9.4 Remote Command Execution and Synchronization.- 21.9.5 PGENESIS Objects.- 21.9.6 Modifiable PGENESIS Parameters.- 21.9.7 Unsupported and Dangerous Operations.- 21.10 Exercises.- 22 Advanced XODUS Techniques: Simulation Visualization.- 22.1 Introduction.- 22.2 What Can Your User Interface Do for You?.- 22.3 Draw/Pix Philosophy.- 22.4 Meet the Cast.- 22.4.1 The Draw Widget Family.- 22.4.2 The Pix Family.- 22.5 XODUS Events.- 22.5.1 Returning Arguments to Script Functions.- 22.6 Using Advanced Widgets: A Network Builder.- 22.6.1 The Library Window.- 22.6.2 Making Prototype Cells.- 22.6.3 The Work Window.- 22.6.4 Editing Cells.- 22.6.5 Connecting Cells.- 22.6.6 Plotting Cell Activity.- 22.6.7 Running Netkit.- 22.6.8 Extending Netkit.- 22.7 Interface vs. Simulation.- 22.8 Summary.- A Acquiring and Installing GENESIS.- A.1 System Requirements.- A.2 Using the CD-ROM.- A.3 Obtaining GENESIS over the Internet.- A.4 Installation and Documentation.- A.5 Copyright Notice.- B GENESIS Script Listings.- B.1 tutorial2.g.- B.2 tutorial3.g.- B.3 tutorial4.g.- B.4 tutorial5.g.- B.5 hhchan.g.- B.6 hhchan_K.g.- B.7 userprefs.g.- B.8 cellproto.g.- Index of GENESIS Commands.- Index of GENESIS Objects.