The Six Modules
HODGKIN-HUXLEY simulates the Hodgkin-Huxley model of a nerve impulse. Two stimulus pulses can be applied in either current clamp or voltage clamp mode, each with square or ramp waveform and user-defined amplitude and timing. A wide range of phenomena can be simulated, including refractory period, threshold accommodation, voltage clamp tail currents, single channel patch clamp conductances and many others. An animated cartoon shows the action of molecular gates in the cell membrane. Various drugs can be applied, and the temperature and ionic concentrations can be varied.
GOLDMAN simulates the Goldman-Hodgkin-Katz constant field equation (known as the Goldman equation for brevity). This allows students to explore the relationship between ionic concentrations and equilibrium potentials, and relative ionic permeability and the membrane potential. It explicitly calculates the Nernst and Goldman equations for a range of ionic parameters.
MEMBRANE PATCH simulates the kinetic properties of single ion channels. Three simple models are supplied: a two-state open/shut channel; a 3-state agonist-activated channel (shut/unbound, shut/bound, open/bound); and a 3-state shut, open, blocked channel. The program can also model a channel with up to 5 states with user-defined transition rate constants. Open-time and shut-time histograms can be displayed, with multi-exponential curves superimposed. A simple burst analysis option is available. Raw data of open and shut times can be exported to ASCII files for more sophisticated analysis.
PASSIVE CONDUCTION simulates the non-spiking conduction properties (the cable properties) of a neuron. The experimental situation is as follows. There is a long non-spiking axon or dendrite of uniform length, into which six microelectrodes are inserted. The electrode at one end of this line is used to inject square pulses of positive or negative current. The other five electrodes are used for measuring voltage. The user can adjust the amplitude, duration and delay of the current pulses, and the location of the five recording electrodes relative to the site of current injection. The user "builds" the axon by setting its membrane characteristics and diameter. The aim is to show how the voltage response to a current pulse varies with time and distance, according to the characteristics of the axon. It demonstrates how signal attenuation relates to the properties of time constant and space constant. Temporal summation can be demonstrated. The membrane potential can be displayed either as a graph of potential against time, or potential against axon location of the recording electrodes.
NETWORK allows the user to construct arbitrary circuits of neurons interconnected by non-spiking or spiking chemical synapses and rectifying or non-rectifying electrical synapses. Many of the membrane properties of each neuron can be set individually, including the option of making a neuron an endogenous burster. Although active membrane events are simplified to maximize speed, spike characteristics such as threshold accommodation can be included. Experimental current pulses of defined amplitude and timing can be injected into any neuron. Many different types of synapses can be defined, including chemical synapses with different reversal potentials, synaptic strengths and facilitation properties, and electrical synapses with different rectification properties. Chemical synapses can be voltage dependent. Tonic or random synaptic input with defined characteristics can impinge on any neuron. These features enable a very wide range of circuit phenomena to be demonstrated, including endogenous and network oscillators, lateral inhibition in sensory systems, and many others. Synapses can be defined with Hebbian properties, where the strength of the connection is augmented when pre- and post-synaptic neurons are co-active, as in long-term potentiation (LTP). A range of features to support investigation of learning and memory processes using such Hebbian synapses are available.
NEURON/SYNAPSE is a single-compartment neuron model in which both voltage-dependent and synaptic conductances can be incorporated. It is intended for investigating more complex cellular systems than that of the standard HH model, but it provides similar current clamp and voltage clamp experimental facilities. Up to nine voltage-dependent channel types can be included, each with user-defined maximum conductance and equilibrium potential, and with activation and inactivation kinetics defined using a built-in equation editor. Intracellular calcium concentration fluctuations can be simulated, and any channel can be made calcium dependent. This means that a wide variety of neuron types can be simulated, including endogenous bursters, neurons with a large A current, etc. The Neuron/Synapse simulation can be used to replicate many classic simulations from the literature, and/or to explore in detail the physiological consequences of variations in channel kinetics and other properties. In addition to the voltage-dependent channels, up to five ligand gated (synaptic) channel types can also be included, each with either a square or alpha-waveform conductance profile and defined maximum conductance and equilibrium potential. Synaptic events can show facilitation or decrement, can be of conductance increase or decrease type, and can show voltage dependence. The parameters for quantal release can be defined for conductance increase synapses, allowing statistical analysis of amplitude fluctuations. This allows the detailed exploration of ionotropic post-synaptic events, and their interaction with voltage-dependent channels.