Long-term potentiation (LTP)

Long-term potentiation can be either associative (Hebbian) or nonassociative. Long-term potentiation at the synapses among CA3 Scs (Schaffer collaterals) and CA1 cells in the hippocampus is Hebbian. It can be learning in hippocampal brain slices through intracellular or extracellular recording from CA1 neurons whilst electrically stimulating a bundle of Schaffer collaterals in the diagram.

Figure:  LTP in a hippocampal slice. (a) Excitatory postsynaptic potentials (epsps) recorded from CA1 pyramidal cells before (control) and after tetanic stimulus (LTP); (b) epsp magnitude remains elevated over several hours.

In response to brief, low frequency stimulation of the Schaffer collaterals the CA1 cells describe a brief epsp due to glutamate release. If a short tetanic burst of high-frequency stimulation is providing like typically 100 Hz for 0.5 s, following low frequency pulses now elicits a larger epsp. This is Long-term potentiation. It can also be studied using chronically implanted electrodes in awake, behaving animals. Long-term potentiation has various properties:

-Input specificity. Delivery of low frequency stimuli to the CA1 cell via a different untetanized bundle of Scs does not elicit the enhanced epsp.

-Cooperativity. The probability of producing Long-term potentiation increases with the number of afferent fibers (Scs) tetanically stimulated. Although weak (i.e., low current) high-frequency stimuli often fail to generate Long-term potentiation because they excite only a few afferents strong tetanic stimuli are successful because they recruit several afferents.

- Associativity. A given CA1 cell receives Scs from CA3 cells on the similar side and commissural axons which come from CA3 cells in the contralateral hippocampus. Weak tetanic stimulus to either pathway that fails to generate Long-term potentiation will do so if it is paired with a strong tetanic stimulus in the other pathway.

- Persistence. It lasts for several minutes (in brain slices) to months when induced in vivo.

This marks it out from other forms of synaptic plasticity.
Two phases of Long-term potentiation are recognized, early (E-LTP) that does not need protein syntheis, and late (L-LTP) that does. Biochemical processes associated with the maintenance, induction and expression of each phase has been described.