Tutorial Exercises and Demonstrations

Tutorial v14 for Neurosim v5.5 (June 2023)

Version

NOTE: The tutorials in this section are written for an earlier version of Neurosim. Tutorials for the latest version (and links to earlier versions) are available here.

If you are actually running Neurosim v5-5-2, you are strongly recommended to install the free upgrade to the latest version.

Tooltips

Within the tutorial text there are occasional tooltips indicated thus This is a tooltip.. If you hover over one of these (or tap it on a touch screen), hopefully-useful information will show.

Parameter files

Within the tutorials there are links to the parameter files displayed thus.

You can download or run Be aware that if you run a file directly from the browser, each file will start a new instance of Neurosim. Also note that with some browsers a local copy of the file may be downloaded to your default Download folder. To prevent disk clutter, you may want to delete these files after you finish your simulation session. parameter files (depending on your browser configuration) by clicking on the link. However, if you would rather download all the parameter files at once and store them locally on your computer, they are available in the compressed file samples-5-5.zip.

There are 5 core tutorial topics:

There are implementation details about the algorithms and methods used in Neurosim

Click on a link in the Contents below to go to a particular topic.

Note: there is much more material here than would be needed or useful for most undergraduate courses. If you are a teacher using Neurosim, you should just select the activities you deem appropriate – and of course feel free to adjust them and/or write your own.

 


Contents

Passive Properties

Resting potential

Nernst equation

Potassium Equilibrium Potential

Temperature Dependence

Concentration Gradient Dependence

Goldman equation

Simple Goldman

Full Goldman

Chloride

Chloride Regulation

Steady State versus Equilibrium: Pumps

Electrogenic Pumps

Permeability vs Conductance

Conductance Asymmetry: Rectification

Spherical Cells: The Membrane as a Resistor-Capacitor (RC) Circuit

Basic RC Properties

Leakage and Capacitive Currents

Input Resistance

Input Resistance is Size Dependent

Membrane Time Constant

Quantifying the Membrane Time Constant

Reality Checks

Measuring the Time Constant

The Falling Phase
Time Constant is Size Independent

Temporal summation: Why the Time Constant Matters

Low-Pass Filter

Phase Delay

Axons and Dendrites: Conduction of Passive Signals

Attenuation and Delay: Basic Properties

The Space (Length) Constant: Attenuation with Distance

Voltage vs Distance Display

Diameter Affects the Space Constant

Why is the Space Constant Diameter-Sensitive?

Spatial Summation: Why the Space Constant Matters

Conduction Velocity

The Time Constant: Time Delay with Distance

Temporal Summation: Why the Time Constant Matters

Input Resistance

The Cable Equation

Non-Uniform Diameter: A Compartmental Model

Spatial Summation

Passive Property Units

 

Action Potentials (Spikes)

Conceptual Summary

Static (Non-Propagating) Spikes

Threshold: All or None?

Sodium Dependence of Spikes

Analysing the Results

Hyperkalaemia

Spike Currents and Conductances

Blocking Sodium and Potassium Channels

Molecular Events and Patch Recordings

Single Channel Patch Recording

Micro and Macro Conductance
The HH Model in Action

Strength-Duration Curve

Rheobase and Chronaxie

Cause of the Strength-Duration Relationship

Ramp Stimulus

Refractory Period

Threshold Accommodation

Rebound Excitation

Post-Inhibitory Facilitation

Pacemaker (continuous spiking)

Spike Propagation (Conduction)

Basic Conduction Features

Conduction Velocity

Spike Collision

Spike Spatial Distribution

Passive vs Active Conduction

Refractory Conduction

Myelination and Saltatory Conduction

Voltage clamp

Theory of the Voltage Clamp

Voltage Clamp Currents: Ionic, Capacitive, Gating

Classic HH Experiments

Sodium I/V Curve

Sodium Equilibrium Potential

Sodium Inactivation

Potassium I/V Curve

Tail Currents

Capacitive Current

Why a Constant Voltage Matters
Space-Clamp Problems

Single Channel Patch Recording

Conductance

Micro and Macro Conductance

Current

Beyond Basic HH Models

Endogenous Burster Neurons

Calcium/Calcium-Dependent Potassium Channels

Phase Resetting

Inactivating Calcium Channels

Channel Kinetics

Conditional bursters

Plateau Potentials

Bi-stable neurons

A Current (Transient Potassium Channels)

Inking in Aplysia

Advanced Kinetics

Voltage-Dependency of Alpha and Beta

Gate Voltage-Dependency

Steady-State Probability

Time Constant of Probability Change

Alpha and Beta during a Spike

Channel Voltage-Dependency

Potassium Channels

Sodium Channels

Putting it all together: finding the membrane potential

Capacitive current (spike)

Non-Ohmic Channels: The GHK Current Equation

Rectification

Conductance

Morris-Lecar: Reduced Kinetics

Equations

Further reduction

Significance

Phase Plane Analysis

Phase Plots of Experimental Data

 

Synapses

Chemical Synapses

Excitation and Inhibition

Integration

Voltage Clamp

Summation and Facilitation

Depolarising and Silent IPSPs

Non-Spiking Synapses

Voltage-Dependent Synapses (NMDA-type)

NMDA I/V Curve

Hebbian Synapses

Quantal Release

Quantal Size Distribution

Electrical Synapses

Frequency Matters

Size Matters

Rectification

Crayfish

Dendritic Computation

Proximal and Distal Inhibition

Directional Sensitivity

 

Networks

Central Pattern Generators

Flip-Flop Circuit

Reciprocal Inhibition Oscillator

Multi-Phase Rhythms

Laser Photoinactivation and Optogenetics

Sensory Feedback

Phase Resetting Tests

Tadpole Swimming: A case study

Basic dIN and cIN Properties

The Core Swimming Circuit

Spike-Triggered Display

Swim Initiation

Short-Term Motor Memory and the Sodium Pump

Synchronization and Entrainment

Entrainment

Synchronization

Metachronal Rhythm

Stochastic Resonance

Dithering

Lateral Inhibition

Pre-Synaptic Inhibition

Primary Afferent Depolarization (PAD)

Inhibition mechanism

Antidromic Spikes and the DRR

The Jeffress Model for Auditory Localization

Phase Ambiguity

Learning Networks

Classical Conditioning: Pavlov’s Dog

Associative Learning: Pattern Completion

Hebbian mechanism

Limitations

Facilities for Memory Models

Wilson Cowan Models

Background Theory

Neurosim Implementation

Stable States

Bi-stable output

Hysteresis

Tri-stable output

Tri-stable mechanism

Oscillations

Phase plane analysis

Multi-Unit Models

Synchronizing oscillations

Anti-phase synchronization

Fly larval crawling

 

Kinetics of Single Ion Channels

Two-State Channels: An Open and Shut Case

Mean Sojourn Duration and Transition Rate Constants

Sojourn Distribution is Exponential

Histogram Analysis

Channel Blocker: Antagonist Effects

Open-Time Distribution

Effect of Blocker Concentration

Closed-Time Distribution is Multi-Exponential

Likelihood and BIC

Why are there 2 Exponentials?

Comparison of Open- and Closed-Time Distributions

What is the Point? A Reminder

A Transmitter-Activated Channel

Open-Time Distributions

Closed-Time Distribution.

Bursts of Open State Conductance

The Acetylcholine Receptor Model

Auto-Correlations

 

Implementation Details

Neurons

Passive Properties

Noise

Spiking Properties

Integrate-and-fire

Spike Threshold Accommodation
Synaptic connections

Without Integrate-and-Fire

Spike generation
Synaptic connections

Voltage-Dependent Channels

Gates

Non-Gate Models

Calcium and Sodium Channels

Variable Equilibrium Potential

Drugs: Blockers, Activators and Optogenetics

Blockers
Activators
Optogenetics

Calcium Dependent Channels

Intracellular Calcium Concentration

Making a Channel Calcium-Dependent

Sodium Pump

Pump Current Sodium Concentration Dependency

Intracellular Sodium Concentration

Limitations

Synapses

Spiking Chemical Synapse

Delay

Shape

Single exponential
Dual exponential

Facilitation

Voltage-Dependent Synapse

Hebbian Synapses

Learning
Forgetting
Linear forgetting
Augmentation-reduced forgetting

Advanced HH Only

Conductance Decrease Synapse
Extracellular Calcium Concentration
Quantal Release

Non-Spiking Chemical Synapses

Direct

Multi-Stage

Carrier Ions: Calcium and Sodium

Electrical Synapses

Rectifying Electrical Synapses

Drugs: Blockers and Activators

Blockers

Activators

Facilitation
Occlusion

Equations and Integration

Exponential Euler Integration

Integration Components

Adaptive Step Size

Wilson-Cowan Integration

 

Compartmental Models

Active Currents

Neurosim Implementation

 

References

 

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