Overview

PyRhO Architecture

PyRhO is composed of several abstraction layers, including the Model layer, Protocol layer and Simulator layer (shown in the architectural schematic below). Choices in each layer are independent or one another, giving a large number of possible combinations to suit many needs for in silico experiments. Additionally, parameters may be fit to each type of kinetic model from experimental data or loaded from the default options of popular opsins. 

For a more detailed introduction along with worked examples, please see our paper. 

Abstraction Layers

Models

PyRhO's kinetic Markov models of opsin dynamics
StatesTransitionsParametersProsCons
 3  3  11  Efficient analytic solution  Single exponential off-phase decay
 4  7  17  Balance of detail and efficiency  Lacks short-pulse dynamics
 6  9  19  Most detailed dynamics  Computationally expensive
Summary of opsin models

Opsin model schematics
Three-state modelFour-state modelSix-state model
 Three-state model

 Four-state model  Six-state model
 
Schematics of PyRhO's opsin models

Protocols

PyRhO comes with several preconfigured and customisable simulation protocols for exploring the dynamics of the models. These include typical system analysis stimuli such as delta functions, step functions and sinusoids, as well as chirps and specialised protocols designed to probe particular features of the opsins including voltage-dependence (rectifier), opsin activation (shortPulse) and dark recovery (recovery). 

Stimulation Protocols
NameTypePurposeVariationsNotes
 step  Discrete  Standard pulse train    
 delta  Discrete  Quick perturbation    
 sinusoid  Continuous  Oscillating pulse  {sine, cosine}  
 chirp  Continuous  Frequency analysis  {linear, exponential}  
 ramp  Continuous  Linearly varying pulse    
 rectifier  Discrete  Assess voltage dependence    
 shortPulse  Discrete  Assess short pulse dynamics    
 recovery  Discrete  Assess dark recovery rate    
 custom  Continuous  Build custom stimulation function  User supplied  
Summary of PyRhO's stimulation protocols

 

Simulators

Python

For opsin-level simulations, PyRhO solves the ordinary differential equations describing the opsin models with numerical integrators under a given set of experimental conditions. This assumes the opsin is essentially in something like a HEK cell where there are no confounding effects of other ion channels. The resultant photocurrents are then calculated and plotted. 

NEURON

If more detailed morphological neuron models are desired, the topology, geometry and biophysics may be specified in a list of hoc files and passed to the NEURON simulator, along with the parameterised opsin model to be inserted into the cell's membrane. Additionally, the compartment name of where to record from should be specified (default: Vcomp='soma') along with the compartmental expression probability (default: expProb=1.0) and the initialisation membrane potential (default: v_init=-65) and whether to use a voltage clamp (default Vclamp=False). If desired, details of NEURON's numerical integrator may also be adjusted (defaults: CVode=False; dt=0.1) to balance the accuracy and runtime of the simulation. 

Brian 2

For network level simulations, groups of spiking neurons may be transfected with a model opsin and simulated with the Brian 2 simulator. Brian is not currently integrated with PyRhO's GUI and so networks for simulation must be specified programmatically (although the opsin parameters may still be fit or loaded from the GUI). A worked example may be found in the demonstration notebook. For further details, examples and tutorials for using Brian, we refer you to the Brian 2 documentation