Neural facilitation

Increase in postsynaptic potential by impulses
Neural facilitation, also known as paired pulse facilitation (PPF), is a phenomenon in neuroscience in which postsynaptic potentials (PSPs) (EPPs, EPSPs or IPSPs) evoked by an impulse are increased when that impulse closely follows a prior impulse. PPF is thus a form of short term synaptic plasticity. The mechanisms underlying neural facilitation are exclusively pre synaptic; broadly speaking, PPF arises due to increased presynaptic concentration leading to a greater release of neurotransmitter containing synaptic vesicles. Neural facilitation may be involved in several neuronal tasks, including simple learning, information processing, and sound source localization.

Early experiments by Del Castillo & Katz in 1954 and Dudel & Kuffler in 1968 showed that facilitation was possible at the neuromuscular junction even if transmitter release does not occur, indicating that facilitation is an exclusively presynaptic phenomenon. Katz and Miledi proposed the residual hypothesis. They attributed the increase in neurotransmitter release to residual or accumulated ("active calcium") within the axon membrane that remains attached to the membrane's inner surface. Katz and Miledi manipulated the concentration within the presynaptic membrane to determine whether or not residual remaining within the terminal after the first impulse caused an increase in neurotransmitter release following the second stimulus. During the first nerve impulse, concentration was either significantly below or nearing that of the second impulse. When concentration was approaching that of the second impulse, facilitation was increased. In this first experiment, stimuli were presented in intervals of 100 ms between the first and second stimuli. An absolute refractory period was reached when intervals were about 10 ms apart. To examine facilitation during shorter intervals, Katz and Miledi directly applied brief depolarizing stimuli to nerve endings. When increasing the depolarizing stimulus from 1 2 ms, neurotransmitter release greatly increased due to accumulation of active Therefore, the degree of facilitation depends on the amount of active , which is determined by the reduction in conductance over time as well as the amount of removed from axon terminals after the first stimulus. Facilitation is greatest when the impulses are closest together because conductance would not return to baseline prior to the second stimulus. Therefore, both conductance and accumulated would be greater for the second impulse when presented shortly after the first. In the Calyx of Held synapse, short term facilitation (STF) has been shown to result from the binding of residual to neuronal sensor 1 (NCS1). Conversely, STF has been shown to decrease when chelators are added to the synapse (causing chelation) which reduce residual Therefore, "active " plays a significant role in neural facilitation. In the synapse between Purkinje cells, short term facilitation has been shown to be entirely mediated by the facilitation of currents through the voltage dependent calcium channels.

Short term synaptic enhancement is often differentiated into categories of facilitation, augmentation, and potentiation (also referred to as post tetanic potentiation or PTP). These three processes are often differentiated by their time scales: facilitation usually lasts for tens of milliseconds, while augmentation acts on a time scale on the order of seconds and potentiation has a time course of tens of seconds to minutes. All three effects increase the probability of neurotransmitter release from the presynaptic membrane, but the underlying mechanism is different for each. Paired pulse facilitation is caused by the presence of residual , augmentation likely arises due to increased action of the presynaptic protein munc 13, and post tetanic potentiation is mediated by presynaptic activation of protein kinases. Many synapses exhibit properties of both facilitation and depression. In general, however, synapses with low initial probability of vesicle release are more likely to exhibit facilitation, and synapses with high probability of initial vesicle release are more likely to exhibit depression. Short term plasticity likely assists in differentiating between these two pathways: short term facilitation dominates in intensity pathways, while short term depression dominates in temporal pathways. These different types of short term plasticity allow for different kinds of information filtration, thus contributing to the division of the two kinds of information into distinct processing streams. The filtering capabilities of short term plasticity may also assist with encoding information related to amplitude modulation (AM). Short term depression can dynamically adjust the gain on high frequency inputs, and may thus allow for an expanded high frequency range for AM. A mixture of facilitation and depression may also assist in AM coding by leading to rate filtering.