and properties of ion channels in the axon or dendrites has the ability to diminish the effects of a hyperstimulated synapse. In the case of extreme overexcitation of these ion channels, backwards flow of ions into the cell will occur, leading to excitotoxicity and cell death by apoptosis or necrosis. Intrinsic mechanisms Nonsynaptic neuronal areas such as the axon also have inherent qualities that affect the synapse. These essential mechanisms include the delay in depolarization that action potential undergoes while traveling down the axon. This intrinsic quality slows the propagation of action potentials and is due to the movement of depolarizing current down the cytoplasm and the intermittent placement of sodium channels on the Nodes of Ranvier. These mechanisms always exist, but may change depending on the conditions of the cell soma, axon, and dendrites at the time. Therefore, latency, or delay in propagation of action potentials or excitatory postsynaptic potentials, can be variable. Every excitatory postsynaptic potential that is propagated to a postsynaptic cell is first transmitted through the action potential down the axon in the presynaptic cell, and thus nonsynaptic plasticity inherently affects synaptic plasticity. Types 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, a response from nonsynaptic plasticity. This response can result from the modulation of certain presynaptic K+ (potassium ion) currents (IA, IK,Ca, and IKs), which work to increase the excitability of the sensory neurons, broaden the action potential, and enhance neurotransmitter release. These modulations of K+ conductances serve as common mechanisms for regulating excitability and synaptic strength. 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