Intrinsic plasticity

Nonsynaptic plasticity is a form of neuroplasticity that involves modification of ion channel function in the axon, dendrites, and cell body that results in specific changes in the integration of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). Nonsynaptic plasticity is a modification of the intrinsic excitability of the neuron. It interacts with synaptic plasticity, but it is considered a separate entity from synaptic plasticity. Intrinsic modification of the electrical properties of neurons plays a role in many aspects of plasticity from homeostatic plasticity to learning and memory itself. Nonsynaptic plasticity affects synaptic integration, subthreshold propagation, spike generation, and other fundamental mechanisms of neurons at the cellular level. These individual neuronal alterations can result in changes in higher brain function, especially learning and memory. However, as an emerging field in neuroscience, much of the knowledge about nonsynaptic plasticity is uncertain and still requires further investigation to better define its role in brain function and behavior. Nonsynaptic plasticity is a form of neuroplasticity that involves modification of ion channel function in the axon, dendrites, and cell body that results in specific changes in the integration of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). Nonsynaptic plasticity is a modification of the intrinsic excitability of the neuron. It interacts with synaptic plasticity, but it is considered a separate entity from synaptic plasticity. Intrinsic modification of the electrical properties of neurons plays a role in many aspects of plasticity from homeostatic plasticity to learning and memory itself. Nonsynaptic plasticity affects synaptic integration, subthreshold propagation, spike generation, and other fundamental mechanisms of neurons at the cellular level. These individual neuronal alterations can result in changes in higher brain function, especially learning and memory. However, as an emerging field in neuroscience, much of the knowledge about nonsynaptic plasticity is uncertain and still requires further investigation to better define its role in brain function and behavior. Neuroplasticity is the ability of a particular part or region of a neuron to change in strength over time. There are two largely recognized categories of plasticity: synaptic and nonsynaptic. Synaptic plasticity deals directly with the strength of the connection between two neurons, including amount of neurotransmitter released from the presynaptic neuron, and the response generated in the postsynaptic neuron. Nonsynaptic plasticity involves modification of neuronal excitability in the axon, dendrites, and soma of an individual neuron, remote from the synapse. Synaptic plasticity is the ability of a synapse between two neurons to change in strength over time. Synaptic plasticity is caused by changes in use of the synaptic pathway, namely, the frequency of synaptic potentials and the receptors used to relay chemical signals. Synaptic plasticity plays a large role in learning and memory in the brain. Synaptic plasticity can occur through intrinsic mechanisms, in which changes in synapse strength occur because of its own activity, or through extrinsic mechanisms, in which the changes in synapse strength occur via other neural pathways. Short-term inhibitory synaptic plasticity often occurs because of limited neurotransmitter supply at the synapse, and long-term inhibition can occur through decreased receptor expression in the postsynaptic cell. Short-term complementary synaptic plasticity often occurs because of residual or increased ion flow in either the presynaptic or postsynaptic terminal, while long-term synaptic plasticity can occur through the increased production of AMPA and NMDA glutamate receptors, among others, in the postsynaptic cell. In comparison, nonsynaptic plasticity is a less well known and somewhat new and ongoing field of research in neuroscience. It is manifested through changes in the characteristics of nonsynaptic structures such as the soma (biology), the axon, or the dendrites. Nonsynaptic plasticity can have short-term or long-term effects. One way these changes occur is through modification of voltage-gated channels in the dendrites and axon, which changes the interpretation of excitatory or inhibitory potentials propagated to the cell. For example, axonal nonsynaptic plasticity can be observed when an action potential fails to reach the presynaptic terminal due to low conduction or buildup of ions. Nonsynaptic and synaptic plasticity have been shown to work concurrently in a variety of ways to produce stimulating effects in the neuron. This includes spike generation, a product of nonsynaptic regulation of potassium and other presynaptic ion channels, which increase the response of the excitatory postsynaptic potential through neurotransmitter release and augmentation of the action potential. Nonsynaptic dendritic plasticity also adds to the effects of synaptic plasticity through widening of the action potential. As will be discussed further, brain-derived neurotrophic factor (BNDF) is produced by neurons to coordinate nonsynaptic and synaptic plasticity. Nonsynaptic changes in the somal body, axon, or dendrites of the neuron are inextricably linked to synaptic strength. Although much more is known about the role of synaptic plasticity in memory and learning, both synaptic and nonsynaptic plasticity are essential to memory and learning in the brain. There is much evidence that the two mechanisms both work to achieve the observed effects synergistically. A key example of this is memory formation in the synapse, in which modification of presynaptic release mechanisms and postsynaptic receptors affects either long-term potentiation or depression. Continuous somal depolarization, on the other hand, has been proposed as a method for learned behavior and memory by nonsynaptic plasticity. Nonsynaptic plasticity also augments the effectiveness of synaptic memory formation by regulation of voltage-gated ion channels. Nonsynaptic plasticity is the mechanism responsible for modifications of these channels in the axon, leading to a change in strength of the neuronal action potential, invariably affecting the strength of synaptic mechanisms, and thus the depth and length of memory encoding. Nonsynaptic plasticity also has the ability to regulate the effects of synaptic plasticity through negative feedback mechanisms. Change in the number 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. 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 EPSPs, 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. 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 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.