Intrinsic excitability of a neuron

The excitability of a neuron at any point depends on the internal and external conditions of the cell at the time of stimulation. Since a neuron typically receives multiple incoming signals at a time, the propagation of an action potential depends on the integration of all the incoming EPSPs and IPSPs arriving at the axon hillock. If the summation of all exitatory and inhibitory signals depolarize the cell membrane to the threshold voltage, an action potential is fired. Changing the intrinsic excitability of a neuron will change that neuron's function.

Axonal modulation

Axonal modulation is a type of plasticity in which the number, activity, or location of ion-channels in the axon changes. This causes the neuron to behave differently when stimulated. The modulation of ion-channels is a response to a change in the stimulation frequencies of a neuron. This is the main form of nonsynaptic plasticity.

Shunting

Shunting is a process in which axonal ion-channels open during the passive flow of a subthreshold depolarization down the axon. Usually ocurring at axonal branch points ^[1] , the timing of these channels opening as the subthreshold signal arrives in the area causes a hyperpolarization to be introduced to the passively flowing depolarization. Therefore, the cell is able to control which branches of the axon the subthreshold depolarization current flows through, resulting in some branches of the axon being more hyperpolarized that others. These differing membrane potentials cause certain areas of the neuron to be more excitable than others, based on the specific location and ocurrence of shunting.

High frequency stimulation

• Short term effects:

High frequency stimulation of a neuron for a short period of time increases the excitability of the neuron by lowering the threshold voltage required to fire an action potential.^[2] High frequency stimulation leads to an increase in the intracellular concentration of sodium ions due to the repeated opening of voltage-gated sodium channels in the axon and terminal. As the frequency of stimuli increases, there is less time between each stimulus for the cell to repolarize and return to normal resting potential. Therefore, the resting potential becomes more depolarized, meaning a smaller depolarizing current is needed to fire an action potential.

However, this modulation is usually very short lived. If the stimulation ceases, the neuron will revert back to its original resting potential as the ion-channels and pumps have ample time to recover from the last stimulus.

• Long term effects:

High frequency stimulation of a neuron over a long period of time causes two resulting neuronal changes. Initially, the neuron responds as it would during short term stimulation, with an increase in excitability. Continuing the high frequency stimulation after this point results in a drastic, non-reversible change in excitability. When sodium concentrations reach a high enough level in the axon, sodium/calcium pumps reverse their direction of flow, causing calcium to be imported into the cell as sodium is exported out. The increased calcium concentration (and subsequent depolarization of the membrane) inactivates sodium channels and targets them for endocytosis and lysosomal hydrolysis.^[3] This results in a major decrease in axonal sodium channels, which are necessary for action potential propagation. If the stimulation continues, eventually the neuron will stop transmitting action potentials and will die.