# 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

.thusYou 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