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Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001.

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Neuroscience. 2nd edition.

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Long-Term Synaptic Potentiation

LTP has been most thoroughly studied in the mammalian hippocampus, an area of the brain that is especially important in the formation and/or retrieval of some forms of memory (see Chapter 31). In humans, functional imaging shows that the human hippocampus is activated during certain kinds of memory tasks, and that damage to the hippocampus results in an inability to form certain types of new memories. In rodents, hippocampal neurons fire action potentials only when an animal is in certain locations. Such “place cells” appear to encode spatial memories, an interpretation supported by the fact that hippocampal damage prevents rats from developing proficiency in spatial learning tasks (Figure 25.4). Although many other brain areas are involved in the complex process of memory formation, storage, and retrieval, these observations have led many investigators to study this particular form of synaptic plasticity in the hippocampus.

Figure 25.4. Spatial learning in rodents.

Figure 25.4

Spatial learning in rodents. (A) Rats are placed in a circular arena (about the size and shape of a child's wading pool) filled with cloudy water. The arena itself is featureless, but the surrounding environment contains the positional cues such as windows, (more...)

Work on LTP began in the early 1970s, when Timothy Bliss and his colleagues at Mill Hill in England discovered that a few seconds of highfrequency electrical stimulation can enhance synaptic transmission in the rabbit hippocampus for days or even weeks. More recently, however, progress in understanding the mechanism of LTP has relied heavily on in vitro studies of slices of living hippocampus. The arrangement of neurons allows the hippocampus to be sectioned such that most of the relevant circuitry is left intact. In such preparations, the cell bodies of the pyramidal neurons lie in a single densely packed layer that is readily apparent (Figure 25.5). This layer is divided into several distinct regions, the major ones being CA1 and CA3. “CA” refers to Cornu Ammon, a Latin name for Ammon's horn—the ram's horn that resembles the shape of the hippocampus. The dendrites of pyramidal cells in the CA1 region form a thick band (the stratum radiatum), where they receive synapses from Schaffer collaterals, the axons of pyramidal cells in the CA3 region. Much of the work on LTP has focused on the synaptic connections between the Schaffer collaterals and CA1 pyramidal cells. Electrical stimulation of Schaffer collaterals generates excitatory postsynaptic potentials (EPSPs) in the postsynaptic CA1 cells (Figure 25.6). If the Schaffer collaterals are stimulated only two or three times per minute, the size of the evoked EPSP in the CA1 neurons remains constant. However, a brief, high-frequency train of stimuli to the same axons causes LTP, which is evident as a long-lasting increase in EPSP amplitude. LTP also occurs at many other synapses, both within the hippocampus and in a variety of other brain regions, including the cortex, amygdala, and cerebellum.

Figure 25.5. Diagram of a section through the rodent hippocampus showing the major regions, excitatory pathways, and synaptic connections.

Figure 25.5

Diagram of a section through the rodent hippocampus showing the major regions, excitatory pathways, and synaptic connections. Long-term potentiation has been observed at each of the three synaptic connections shown here.

Figure 25.6. Long-term potentiation of Schaffer collateral-CA1 synapses.

Figure 25.6

Long-term potentiation of Schaffer collateral-CA1 synapses. (A) Arrangement for recording synaptic transmission; two stimulating electrodes (1 and 2) each activate separate populations of Schaffer collaterals, thus providing test and control synaptic (more...)

LTP of the Schaffer collateral synapse exhibits several properties that make it an attractive neural mechanism for information storage. First, LTP is state-dependent: The degree of depolarization of the postsynaptic cell determines whether or not LTP occurs (Figure 25.7). If a single stimulus to the Schaffer collaterals—which would not normally elicit LTP—is paired with strong depolarization of the postsynaptic CA1 cell, the size of the EPSP is increased. The increase occurs only if the paired activities of the presynaptic and postsynaptic cells are tightly linked in time, such that the strong postsynaptic depolarization occurs within about 100 ms of presynaptic transmitter release. Recall that a requirement for coincident activation of presynaptic and postsynaptic elements is the hallmark of the Hebbian postulate (see Chapter 24), an early attempt to establish a theoretical framework of the synaptic changes underlying learning and memory.

Figure 25.7. Pairing presynaptic and postsynaptic activity causes LTP.

Figure 25.7

Pairing presynaptic and postsynaptic activity causes LTP. Single stimuli applied to a Schaffer collateral synaptic input evokes EPSPs in the postsynaptic CA1 neuron. These stimuli alone do not elicit any change in synaptic strength. However, when the (more...)

LTP also exhibits the property of input specificity: When LTP is induced by the stimulation of one synapse, it does not occur in other, inactive synapses that contact the same neuron (see Figure 25.6). Thus, LTP is input-specific in the sense that it is restricted to activated synapses rather than to all of the synapses on a given cell (Figure 25.8A). This feature of LTP is consistent with its involvement in memory formation. If activation of one set of synapses led to all other synapses—even inactive ones—being potentiated, it would be difficult to selectively enhance particular sets of inputs, as is presumably required for learning and memory (see also Box B).

Figure 25.8. Properties of LTP at a CA1 pyramidal neuron receiving synaptic inputs from two independent sets of Schaffer collateral axons.

Figure 25.8

Properties of LTP at a CA1 pyramidal neuron receiving synaptic inputs from two independent sets of Schaffer collateral axons. (A) Strong activity initiates LTP at active synapses (pathway 1) without initiating LTP at nearby inactive synapses (pathway (more...)

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Box B

Silent Synapses. Several recent observations indicate that excitatory synapses can dynamically regulate their postsynaptic glutamate receptors. Early insight into this process came from the finding that stimulation of some glutamatergic synapses generates (more...)

Another important property of LTP is associativity (Figure 25.8B). As noted, weak stimulation of a pathway will not by itself trigger LTP. However, if one pathway is weakly activated at the same time that a neighboring pathway onto the same cell is strongly activated, both synaptic pathways undergo LTP. This selective enhancement of conjointly activated sets of synaptic inputs is often considered a cellular analog of associative or classical conditioning. More generally, associativity is expected in any network of neurons that links one set of information with another.

Although there is clearly a gap between understanding LTP of hippocampal synapses and understanding behavioral plasticity, this form of synaptic plasticity provides a plausible neural mechanism for long-lasting changes in a part of the brain that is known to be involved in the formation of certain kinds of memories.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2001, Sinauer Associates, Inc.
Bookshelf ID: NBK10878

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