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 excitatory and inhibitory postsynaptic potentials arriving at the
axon hillock. If the summation of all excitatory 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.
Spike generation Nonsynaptic plasticity has an excitatory effect on the generation of
spikes. The increase in spike generation has been correlated with a decrease in the
spike threshold,
Regulation of synaptic plasticity Nonsynaptic plasticity has been linked with synaptic plasticity, via both synergistic and regulatory mechanisms. The degree of synaptic modification determines the
polarity of nonsynaptic changes, affecting the change in cellular excitability. Moderate levels of synaptic plasticity produce nonsynaptic changes that will synergistically act with the synaptic mechanisms to strengthen a response. Conversely, more robust levels of synaptic plasticity will produce nonsynaptic responses that will act as a
negative feedback mechanism. The negative feedback mechanisms work to protect against saturation or suppression of the circuit activity as a whole.
Shunting Shunting is a process in which axonal ion channels open during the passive flow (not requiring an
ion pump) of a subthreshold
depolarization down the axon. Usually occurring at axonal branch points, 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 than others. These differing membrane potentials cause certain areas of the neuron to be more excitable than others, based on the specific location and occurrence 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 amount of
voltage required to fire an action potential. 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. Neuronal death due to overstimulation is called
excitotoxicity.
Low frequency stimulation Short-term effects: All living neurons have a basal rate of action potential propagation and synaptic release. Thus, low frequency stimulation of a neuron in the short term is similar to the activity of a neuron at rest in the brain. No major changes happen to the intrinsic excitability of the neuron. Long-term effects: Low frequency stimulation of a neuron for a long period of time decreases the excitability of the neuron by activating calcium-dependent phosphatases that tag
AMPA receptors for internalization. Low frequency stimulation leads to low levels of calcium in the cell. When calcium concentrations are low, active calcium-dependent phosphatases dominate over calcium-dependent kinases. As more phosphatases are activated, they tag more AMPA receptors for internalization through endocytosis. Since AMPA receptors are one of the main excitatory receptors on neurons, removing them from the cell membrane effectively depresses the cell (if the cell cannot react to excitatory signals, it cannot generate an action potential of its own). In this way low frequency stimulation can actually reverse the effects of
long-term potentiation, however these concepts are generally considered types of synaptic plasticity.
Homeostatic and Hebbian plasticity Central nervous system (CNS) neurons integrate signals from many neurons. In the short term, it is important to have changes in activity of the neuron because this is how information is conveyed in the nervous system (
Hebbian plasticity). However, for long-term sustainability, drift towards excitability or inexcitability will disturb the circuit's ability to convey information (
homeostatic plasticity). Long-term potentiation (LTP) induces a higher firing rate in post synaptic neurons. It has been hypothesized that the intrinsic properties of a neuron should be arranged to make the most of the dynamic range, acting as a homeostatic mechanism. However, it was shown that intrinsic excitability follows a lognormal distribution which requires active, Hebbian learning to be kept up.
In vitro studies have found that when the
spontaneous activity of neuronal cultures is inhibited, the neurons become hyper excitable and that when an increase in activity is induced for long periods, the firing rates of the culture drop. In contrast, there is a wealth of evidence that the opposite form of regulation, Hebbian learning or LTP-IE/LTD-IE, also occurs and theoretical arguments show that
Hebbian plasticity must be the dominant form of plasticity for intrinsic excitability as well. an earlier view suggesting that homeostatic plasticity and intrinsic plasticity are linked was shown to be inconsistent with evidence.
Mechanism One mechanism for preserving the dynamic range of a neuron is
synaptic scaling, a homeostatic form of plasticity that restores neuronal activity to its normal 'baseline' levels by changing the postsynaptic response of synapses of a neuron as a function of activity. Homeostatic modulation of the intrinsic excitability of a neuron is another way to maintain stability. The regulation of
ionic conductances can be achieved in a number of ways, mostly through the release of neuromodulators like
dopamine,
serotonin etc. Another way is through the controlled release of brain-derived
neurotrophic factor (BDNF). BDNF has also been found to influence synaptic scaling, suggesting that this neurotrophic factor may be responsible for the coordination of synaptic and nonsynaptic mechanisms in homeostatic plasticity. Dendritic excitability is important for the propagation and integration of synaptic signals. Dendritic excitability is thought to contribute to E-S potentiation, or an increase in the probability that a given input will result in the firing of an action potential. It is known that changes in dendritic excitability affect action potential back propagation. Action potentials begin near the axon hillock and propagate down the length of the axon, but they also propagate backward through the soma into the dendritic arbor. Active back propagation is dependent on ion channels and changing the densities or properties of these channels can influence the degree to which the signal is
attenuated. Back propagation is a method of signaling to the synapses that an action potential was fired. This is important for
spike-timing-dependent plasticity. Fast dendritic adaptation on timescales of few seconds was experimentally observed indicating a potential meaningful global learning mechanism
Intrinsic plasticity Intrinsic plasticity is a form of
activity-dependent plasticity distinct from
synaptic plasticity, which involves changes at the synapse between two neurons rather than changes in the electrical properties within a single neuron. There are some closely related phenomena that can affect a neuron's excitability – such as
neuromodulation, structural plasticity, short-term plasticity due to channel kinetics, and
neural development. There is no consensus on the quantity that intrinsic plasticity regulates, e.g. the firing rate of a neuron, its gain or its internal calcium concentration. Functionally, intrinsic plasticity might allow neurons to learn the intensity of stimuli and represent those intensity statistics in their excitabilities. Intrinsic plasticity contributes to encoding memory and complements other forms of activity-dependent plasticity including
synaptic plasticity. ==Higher brain function==