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Module 13 LTP NBL 656

Terms in this set (49)

The features of LTP: long term/persistent, cooperative and associative, input (synapse) specific (also called Hebbian), reversible, and saturable.

LTP is Input specific/Hebbian: Only pathways (synapses) that receive input (axonal stimulation) can be strengthened. LTP is input specific and requires coincident presynaptic and postsynaptic stimulation. In tetanic stimulation of the SC, glutamate must bind and activate both the AMPARs (which cause depolarization) and activation of NMDARs to allow Ca2+ influx. For the SC, both the presynaptic stimulation and postsynaptic depolarization must be temporally linked to ensure NMDAR activation (since the NMDAR requires both glutamate binding and depolarization, which removes the Mg2+ block, to be activated). If no glutamate or no activation of NMDARs and Ca2+ influx, no LTP occurs. Tetanic stimulation of the SC is not physiological (it is much more activity than this pathway normally has). In a more physiological setting, the postsynaptic depolarizations are most likely caused by multiple small EPSPs that are produced by excitatory inputs that arrive at the postsynaptic neuron at about the same time. Thus there would be presynaptic release of glutamate (but at a much lower level than in the tetanic stimulus) and the postsynaptic depolarization would occur through the summed EPSPs of multiple nearby synapses within a short time period. This would lead to strengthening of all the active glutamate synapses in the dendritic region that received the concomitant inputs.

LTP is Associative: Weak stimulation of an axon and low levels of glutamate release at synapse 1 cannot induce LTP (and may induce LTD). However, if there is strong stimulation to a nearby synapse 2 that occurs at the same time as the weak input to synapse 1, then LTP can occur at both synapses. Mechanism: the strong stimulation at synapse 2 produces a large depolarization which will spread/move along the membrane (as the Na+ ions diffuse) and this will depolarize the membrane at synapse 1, and relieve the NMDAR Mg2+ block from synapse 1. Since synapse 1 also has input/glutamate, the NMDARs will be activated, Ca2+ will flow in and LTP will be induced. From Wiki: "Associativity refers to the observation that when weak stimulation of a single pathway is insufficient for the induction of LTP, simultaneous strong stimulation of another pathway will induce LTP at both pathways.

LTP is Cooperative: LTP requires that presynaptic stimulation be linked temporally with postsynaptic depolarization. In the non-physiological experimental paradigm, this involves prolonged high frequency stimulation (tetanic); repeated bursts of 4 pulses (theta); or, a pairing between induced postsynaptic depolarization and low frequency presynaptic stimulation.
Under physiological situations, induction can be cooperative, since many weak signals to a neuron can cooperatively cause sufficient postsynaptic depolarization (even if on its own, each would be insufficient to produce LTP by itself.) From Wiki "LTP can be induced either by strong tetanic stimulation of a single pathway to a synapse, or cooperatively via the concomitant weaker stimulation of many pathways. When one pathway into a synapse is stimulated weakly, it produces insufficient postsynaptic depolarization to induce LTP. In contrast, when weak stimuli are applied to many pathways that converge on a single patch of postsynaptic membrane, the individual postsynaptic depolarizations generated may collectively depolarize the postsynaptic cell enough to induce LTP cooperatively.

Associative and Cooperative May be Similar. Associativity refers to the requirement for coincident timing of presynaptic glutamate release and postsynaptic depolarization. Cooperativity refers to the requirement for enough coincident activity to produce enough depolarization to relieve the Mg2+ block of the NMDA receptors. Some neuroscientists argue that any difference between associativity and cooperativity is strictly semantic. Synaptic tagging, discussed later, may be a common mechanism underlying associativity and cooperativity.

LTP is Reversible: Stimulation of the SC with a tetanus or theta burst stimulation (TBS) will induce LTP. After LTP has been induced, stimulation of that same SC with a low frequency stimulation will reverse the LTP and the response will return to its pre-stimulation level, and even undergo LTD. Likewise, if LTD is induced first with low frequency stimulation of the SC, if this is then followed by a tetanus or TBS, the synaptic response will return to the pre-stimulation level, and even undergo LTP. This is an important feature of LTP/LTD since it is consistent with reversible biochemical pathways such as protein phosphorylation and dephosphorylation, membrane trafficking in exocytosis and endocytosis, and mRNA and protein turnover (synthesis and degradation).

LTP is Saturable: There is a maximal level of increase in LTP or decrease in LTD that can be achieved. So even if one stimulated with a longer time with a higher frequency tetanus for LTP, or lower frequency stimulation for LTD, the magnitude of LTP or LTD cannot be increased beyond a certain level. Presumably this means that there is a maximum and minimum to the volume of the spine and size of the synapse. This is also consistent with biochemical mechanisms underlying long term plasticity.

LTP is Persistent: From Wiki: "LTP is persistent, lasting from several minutes to many months, and it is this persistence that separates LTP from other forms of synaptic plasticity (such as post-tetanic potentiation, a type of short term plasticity)."
Note that LTD has been shown to have the same types of features/characteristics, including reversibility, input specificity, cooperativity/associativity, saturability and persistence.