
Biophysics of Computation
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Content
- Cover
- Contents
- Preface
- List of Symbols
- Introduction
- 1 The Membrane Equation
- 1.1 Structure of the Passive Neuronal Membrane
- 1.1.1 Resting Potential
- 1.1.2 Membrane Capacity
- 1.1.3 Membrane Resistance
- 1.2 A Simple RC Circuit
- 1.3 RC Circuits as Linear Systems
- 1.3.1 Filtering by RC Circuits
- 1.4 Synaptic Input
- 1.5 Synaptic Input Is Nonlinear
- 1.5.1 Synaptic Input, Saturation, and the Membrane Time Constant
- 1.5.2 Synaptic Interactions among Excitation and Shunting Inhibition
- 1.5.3 Gain Normalization in Visual Cortex and Synaptic Input
- 1.6 Recapitulation
- 2 Linear Cable Theory
- 2.1 Basic Assumptions Underlying One-Dimensional Cable Theory
- 2.1.1 Linear Cable Equation
- 2.2 Steady-State Solutions
- 2.2.1 Infinite Cable
- 2.2.2 Finite Cable
- 2.3 Time-Dependent Solutions
- 2.3.1 Infinite Cable
- 2.3.2 Finite Cable
- 2.4 Neuronal Delays and Propagation Velocity
- 2.5 Recapitulation
- 3 Passive Dendritic Trees
- 3.1 Branched Cables
- 3.1.1 What Happens at Branch Points?
- 3.2 Equivalent Cylinder
- 3.3 Solving the Linear Cable Equation for Branched Structures
- 3.3.1 Exact Methods
- 3.3.2 Compartmental Modeling
- 3.4 Transfer Resistances
- 3.4.1 General Definition
- 3.4.2 An Example
- 3.4.3 Properties of K[sub(ij)]
- 3.4.4 Transfer Resistances in a Pyramidal Cell
- 3.5 Measures of Synaptic Efficiency
- 3.5.1 Electrotonic Distance
- 3.5.2 Voltage Attenuation
- 3.5.3 Charge Attenuation
- 3.5.4 Graphical Morphoelectrotonic Transforms
- 3.6 Signal Delays in Dendritic Trees
- 3.6.1 Experimental Determination of T[sub(m)]
- 3.6.2 Local and Propagation Delays in Dendritic Trees
- 3.6.3 Dependence of Fast Synaptic Inputs on Cable Parameters
- 3.7 Recapitulation
- 4 Synaptic Input
- 4.1 Neuronal and Synaptic Packing Densities
- 4.2 Synaptic Transmission Is Stochastic
- 4.2.1 Probability of Synaptic Release p
- 4.2.2 What Is the Synaptic Weight?
- 4.3 Neurotransmitters
- 4.4 Synaptic Receptors
- 4.5 Synaptic Input as Conductance Change
- 4.5.1 Synaptic Reversal Potential in Series with an Increase in Conductance
- 4.5.2 Conductance Decreasing Synapses
- 4.6 Excitatory NMDA and Non-NMDA Synaptic Input
- 4.7 Inhibitory GABAergic Synaptic Input
- 4.8 Postsynaptic Potential
- 4.8.1 Stationary Synaptic Input
- 4.8.2 Transient Synaptic Input
- 4.8.3 Infinitely Fast Synaptic Input
- 4.9 Visibility of Synaptic Inputs
- 4.9.1 Input Impedance in the Presence of Synaptic Input
- 4.10 Electrical Gap Junctions
- 4.11 Recapitulation
- 5 Synaptic Interactions in a Passive Dendritic Tree
- 5.1 Nonlinear Interaction among Excitation and Inhibition
- 5.1.1 Absolute versus Relative Suppression
- 5.1.2 General Analysis of Synaptic Interaction in a Passive Tree
- 5.1.3 Location of the Inhibitory Synapse
- 5.1.4 Shunting Inhibition Implements a "Dirty" Multiplication
- 5.1.5 Hyperpolarizing Inhibition Acts Like a Linear Subtraction
- 5.1.6 Functional Interpretation of the Synaptic Architecture and Dendritic Morphology: AND-NOT Gates
- 5.1.7 Retinal Directional Selectivity and Synaptic Logic
- 5.2 Nonlinear Interaction among Excitatory Synapses
- 5.2.1 Sensitivity of Synaptic Input to Spatial Clustering
- 5.2.2 Cluster Sensitivity for Pattern Discrimination
- 5.2.3 Detecting Coincident Input from the Two Ears
- 5.3 Synaptic Microcircuits
- 5.4 Recapitulation
- 6 The Hodgkin-Huxley Model of Action Potential Generation
- 6.1 Basic Assumptions
- 6.2 Activation and Inactivation States
- 6.2.1 Potassium Current I[sub(K)]
- 6.2.2 Sodium Current I[sub(Na)]
- 6.2.3 Complete Model
- 6.3 Generation of Action Potentials
- 6.3.1 Voltage Threshold for Spike Initiation
- 6.3.2 Refractory Period
- 6.4 Relating Firing Frequency to Sustained Current Input
- 6.5 Action Potential Propagation along the Axon
- 6.5.1 Empirical Determination of the Propagation Velocity
- 6.5.2 Nonlinear Wave Propagation
- 6.6 Action Potential Propagation in Myelinated Fibers
- 6.7 Branching Axons
- 6.8 Recapitulation
- 7 Phase Space Analysis of Neuronal Excitability
- 7.1 The FitzHugh-Nagumo Model
- 7.1.1 Nullclines
- 7.1.2 Stability of the Equilibrium Points
- 7.1.3 Instantaneous Current Pulses: Action Potentials
- 7.1.4 Sustained Current Injection: A Limit Cycle Appears
- 7.1.5 Onset of Nonzero Frequency Oscillations: The Hopf Bifurcation
- 7.2 The Morris-Lecar Model
- 7.2.1 Abrupt Onset of Oscillations
- 7.2.2 Oscillations with Arbitrarily Small Frequencies
- 7.3 More Elaborate Phase Space Models
- 7.4 Recapitulation
- 8 Ionic Channels
- 8.1 Properties of Ionic Channels
- 8.1.1 Biophysics of Channels
- 8.1.2 Molecular Structure of Channels
- 8.2 Kinetic Model of the Sodium Channel
- 8.3 From Stochastic Channels to Deterministic Currents
- 8.3.1 Probabilistic Interpretation
- 8.3.2 Spontaneous Action Potentials
- 8.4 Recapitulation
- 9 Beyond Hodgkin and Huxley: Calcium and Calcium-Dependent Potassium Currents
- 9.1 Calcium Currents
- 9.1.1 Goldman-Hodgkin-Katz Current Equation
- 9.1.2 High-Threshold Calcium Current
- 9.1.3 Low-Threshold Transient Calcium Current
- 9.1.4 Low-Threshold Spike in Thalamic Neurons
- 9.1.5 N-Type Calcium Current
- 9.1.6 Calcium as a Measure of the Spiking Activity of the Neuron
- 9.2 Potassium Currents
- 9.2.1 Transient Potassium Currents and Delays
- 9.2.2 Calcium-Dependent Potassium Currents
- 9.3 Firing Frequency Adaptation
- 9.4 Other Currents
- 9.5 An Integrated View
- 9.6 Recapitulation
- 10 Linearizing Voltage-Dependent Currents
- 10.1 Linearization of the Potassium Current
- 10.2 Linearization of the Sodium Current
- 10.3 Linearized Membrane Impedance of a Patch of Squid Axon
- 10.4 Functional Implications of Quasi-Active Membranes
- 10.4.1 Spatio-Temporal Filtering
- 10.4.2 Temporal Differentiation
- 10.4.3 Electrical Tuning in Hair Cells
- 10.5 Recapitulation
- 11 Diffusion, Buffering, and Binding
- 11.1 Diffusion Equation
- 11.1.1 Random Walk Model of Diffusion
- 11.1.2 Diffusion in Two or Three Dimensions
- 11.1.3 Diffusion Coefficient
- 11.2 Solutions to the Diffusion Equation
- 11.2.1 Steady-State Solution for an Infinite Cable
- 11.2.2 Time-Dependent Solution for an Infinite Cable
- 11.2.3 Square-Root Relationship of Diffusion
- 11.3 Electrodiffusion and the Nernst-Planck Equation
- 11.3.1 Relationship between the Electrodiffusion Equation and the Cable Equation
- 11.3.2 An Approximation to the Electrodiffusion Equation
- 11.4 Buffering of Calcium
- 11.4.1 Second-Order Buffering
- 11.4.2 Higher Order Buffering
- 11.5 Reaction-Diffusion Equations
- 11.5.1 Experimental Visualization of Calcium Transients in Diffusion-Buffered Systems
- 11.6 Ionic Pumps
- 11.7 Analogy between the Cable Equation and the Reaction-Diffusion Equation
- 11.7.1 Linearization
- 11.7.2 Chemical Dynamics and Space and Time Constants of the Diffusion Equation
- 11.8 Calcium Nonlinearities
- 11.9 Recapitulation
- 12 Dendritic Spines
- 12.1 Natural History of Spines
- 12.1.1 Distribution of Spines
- 12.1.2 Microanatomy of Spines
- 12.1.3 Induced Changes in Spine Morphology
- 12.2 Spines only Connect
- 12.3 Passive Electrical Properties of Single Spines
- 12.3.1 Current Injection into a Spine
- 12.3.2 Excitatory Synaptic Input to a Spine
- 12.3.3 Joint Excitatory and Inhibitory Input to a Spine
- 12.3.4 Geniculate Spine Triad
- 12.4 Active Electrical Properties of Single Spines
- 12.5 Effect of Spines on Cables
- 12.6 Diffusion in Dendritic Spines
- 12.6.1 Solutions of the Reaction-Diffusion Equation for Spines
- 12.6.2 Imaging Calcium Dynamics in Single Dendritic Spines
- 12.7 Recapitulation
- 13 Synaptic Plasticity
- 13.1 Quantal Release
- 13.2 Short-Term Synaptic Enhancement
- 13.2.1 Facilitation Is an Increase in Release Probability
- 13.2.2 Augmentation and Posttetanic Potentiation
- 13.2.3 Synaptic Release and Presynaptic Calcium
- 13.3 Long-Term Synaptic Enhancement
- 13.3.1 Long-Term Potentiation
- 13.3.2 Short-Term Potentiation
- 13.4 Synaptic Depression
- 13.5 Synaptic Algorithms
- 13.5.1 Hebbian Learning
- 13.5.2 Temporally Asymmetric Hebbian Learning Rules
- 13.5.3 Sliding Threshold Rule
- 13.5.4 Short-Term Plasticity
- 13.5.5 Unreliable Synapses: Bug or Feature?
- 13.6 Nonsynaptic Plasticity
- 13.7 Recapitulation
- 14 Simplified Models of Individual Neurons
- 14.1 Rate Codes, Temporal Coding, and All of That
- 14.2 Integrate-and-Fire Models
- 14.2.1 Perfect or Nonleaky Integrate-and-Fire Unit
- 14.2.2 Forgetful or Leaky Integrate-and-Fire Unit
- 14.2.3 Other Variants
- 14.2.4 Response Time of Integrate-and-Fire Units
- 14.3 Firing Rate Models
- 14.3.1 Comparing the Dynamics of a Spiking Cell with a Firing Rate Cell
- 14.4 Neural Networks
- 14.4.1 Linear Synaptic Interactions Are Common to Almost All Neural Networks
- 14.4.2 Multiplicative Interactions and Neural Networks
- 14.5 Recapitulation
- 15 Stochastic Models of Single Cells
- 15.1 Random Processes and Neural Activity
- 15.1.1 Poisson Process
- 15.1.2 Power Spectrum Analysis of Point Processes
- 15.2 Stochastic Activity in Integrate-and-Fire Models
- 15.2.1 Interspike Interval Histogram
- 15.2.2 Coefficient of Variation
- 15.2.3 Spike Count and Fano Factor
- 15.2.4 Random Walk Model of Stochastic Activity
- 15.2.5 Random Walk in the Presence of a Leak
- 15.3 What Do Cortical Cells Do?
- 15.3.1 Cortical Cells Fire Randomly
- 15.3.2 Pyramidal Cells: Integrator or Coincidence Detector
- 15.3.3 Temporal Precision of Cortical Cells
- 15.4 Recapitulation
- 16 Bursting Cells
- 16.1 Intrinsically Bursting Cells
- 16.2 Mechanisms for Bursting
- 16.3 What Is the Significance of Bursting?
- 16.4 Recapitulation
- 17 Input Resistance, Time Constants, and Spike Initiation
- 17.1 Measuring Input Resistances
- 17.1.1 Membrane Chord Conductance
- 17.1.2 Membrane Slope Conductance
- 17.2 Time Constants for Active Systems
- 17.3 Action Potential Generation and the Question of Threshold
- 17.3.1 Current-Voltage Relationship
- 17.3.2 Stability of the Membrane Voltage
- 17.3.3 Voltage Threshold
- 17.3.4 Current Threshold
- 17.3.5 Charge Threshold
- 17.3.6 Voltage versus Current Threshold
- 17.4 Action Potential
- 17.5 Repetitive Spiking
- 17.5.1 Discharge Curve
- 17.5.2 Membrane Potential during Spiking Activity
- 17.6 Recapitulation
- 18 Synaptic Input to a Passive Tree
- 18.1 Action of a Single Synaptic Input
- 18.1.1 Unitary Excitatory Postsynaptic Potentials and Currents
- 18.1.2 Utility of Measures of Synaptic Efficacy
- 18.1.3 What Do Unitary EPSPs and EPSCs Tell Us about the Threshold?
- 18.2 Massive Synaptic Input
- 18.2.1 Relationship between Synaptic Input and Spike Output Jitter
- 18.2.2 Cable Theory for Massive Synaptic Input
- 18.3 Effect of Synaptic Background Activity
- 18.3.1 Input Resistance
- 18.3.2 Time Constant
- 18.3.3 Electroanatomy
- 18.3.4 Resting Potential
- 18.3.5 Functional Implications
- 18.4 Relating Synaptic Input to Output Spiking
- 18.4.1 Somatic Current from Distal Synaptic Input
- 18.4.2 Relating f[sub(out)] to f[sub(in)]
- 18.4.3 Functional Considerations
- 18.5 Shunting Inhibition Acts Linearly
- 18.6 Recapitulation
- 19 Voltage-Dependent Events in the Dendritic Tree
- 19.1 Experimental Evidence for Voltage-Dependent Dendritic Membrane Conductances
- 19.1.1 Fast Dendritic Spikes
- 19.2 Action Potential Initiation in Cable Structures
- 19.2.1 Effect of Dendritic Geometry on Spike Initiation
- 19.2.2 Biophysical Modeling of Antidromic Spike Invasion
- 19.3 Synaptic Input into Active Dendrites: Functional Considerations
- 19.3.1 Back-Propagating Spike as Acknowledgment Signal
- 19.3.2 Implementing Logic Computations with Spikes in Spines
- 19.3.3 Coincidence Detection with Dendritic Spikes
- 19.3.4 Nonlinear Spatial Synaptic Interactions Using Active Currents
- 19.3.5 Graded Amplification of Distal Synaptic Input
- 19.4 Recapitulation
- 20 Unconventional Computing
- 20.1 A Molecular Flip-Flop
- 20.1.1 Autophosphorylating Kinases
- 20.1.2 CaM Kinase II and Synaptic Information Storage
- 20.2 Extracellular Resources and Presynaptic Inhibition
- 20.3 Computing with Puffs of Gas
- 20.4 Programming with Peptides
- 20.5 Routing Information Using Neuromodulators
- 20.6 Recapitulation
- 21 Computing with Neurons: A Summary
- 21.1 Is a Biophysics of Computation Possible?
- 21.1.1 The Many Ways to Multiply
- 21.1.2 A Large Number of Biophysical Mechanisms for Computation
- 21.1.3 Can Different Biophysical Mechanisms Be Selected For?
- 21.2 Strategic Questions or How to Find a Topic for a Ph.D. Thesis
- Appendix A: Passive Membrane Parameters
- A.1 Intracellular Resistivity R[sub(i)]
- A.2 Membrane Resistance R[sub(m)]
- A.3 Membrane Capacitance C[sub(m)]
- Appendix B: A Miniprimer on Linear Systems Analysis
- Appendix C: Sparse Matrix Methods for Modeling Single Neurons
- C. 1 Linear Cable Equation
- C.1.1 Unbranched Cables and Tridiagonal Matrices
- C.1.2 Branched Cables and Hines Matrices
- C.1.3 Boundary Conditions
- C.1.4 Eigensystems and Model Fitting
- C.1.5 Green's Functions and Matrix Inverses
- C.2 Nonlinear Cable Equations
- C.2.1 Generalized Hodgkin-Huxley Equations
- C.2.2 Calcium Buffering
- C.2.3 Conclusion
- References
- Index
- A
- B
- C
- D
- E
- F
- G
- H
- I
- J
- K
- L
- M
- N
- O
- P
- Q
- R
- S
- T
- U
- V
- W
- Z
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