Memory: maintenance is presynaptic

Article Abstract:

Long-term potentiation has long been regarded as a model for memory formation in neurons, the cells of the nervous system. In this effect, the high-frequency stimulation of cells in the hippocampus of the brain results in a long-lasting increase in efficiency of synaptic transmission between nerve cells. The molecular mechanisms which are at work in creating and sustaining this increase have been the object of considerable research. For a long time, the evidence seemed to point to a postsynaptic location of the changes. That is, the changes involved in long-term potentiation seemed to be happening in the cell which receives the synaptic transmission, rather than in the cell which initiates it. However, some evidence has accumulated recently suggesting that the reverse is true. In an article in the August 23, 1990 issue of the journal Nature, researchers described their use of quantal analysis to show that long-term potentiation results in an increase in the probability that a nerve impulse will result in the release of neurotransmitter. Quantal analysis is an essentially statistical technique. It is straightforward in the case of muscle cells, where a muscle cell is stimulated only by a single neuron. However, in the hippocampus, as in the rest of the brain, a single neuron may be stimulated by a multitude of other cells. It becomes more difficult to attribute an observed event to any one particular cause. Ultimately, the evidence is interpreted by showing which statistical model best fits the data, rather than by conclusively demonstrating the presynaptic location of the effect. The last word on long-term potentiation is certainly not in. Postsynaptic changes might still be involved in the effect. Perhaps more significantly, postsynaptic changes are clearly involved in the early stages after stimulation. If early changes in the postsynaptic cell result in more permanent changes in the presynaptic cell, the question arises about how the changes are communicated back to the presynaptic cell. The results presented in Nature no doubt will stimulate more research on this question. (Consumer Summary produced by Reliance Medical Information, Inc.)

editorial

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Presynaptic mechanism for the long-term potentiation in the hippocampus

Article Abstract:

Ever since long-term potentiation was first observed in the hippocampus of the brain, neurophysiologists have sought to determine if the phenomenon results from presynaptic changes in the cell sending the synaptic message, or from postsynaptic changes in the neuron receiving it. Long-term potentiation, or LTP, is an increase in the efficiency of synapses which persists long after a transient high-frequency stimulation of the hippocampus; the phenomenon is widely regarded as a useful model for understanding the changes which occur during the consolidation of memory. Traditionally, the analysis of synaptic events to determine if they are pre- or postsynaptic relied upon quantal analysis. In this procedure, statistical methods are used to analyze the electrophysiological results of stimulation, results which are generally the sum of individual "quanta" or packets of neurotransmitter substance. The technique is effective in muscle cells, where there is only a single input to the system. In neurons of the brain, there may be thousands of inputs, and it is difficult to tease apart the effects of each. Furthermore, the effects of individual "quanta", as observed by a recording electrode, will vary tremendously depending on the distance and nature of the cellular terrain intervening between the synapse and the experimenter's electrode. However, researchers have managed to overcome these obstacles by carefully and laboriously obtaining electrophysiological recordings from slices of rat hippocampus maintained in culture dishes. Inferring the characteristics of the synaptic transmission from the statistical distribution of tiny electrical signals, the investigators determined that long-term potentiation results from an increase in the probability of release of a packet of transmitter substance. Since it is difficult to imagine that this could be anything except a presynaptic change, the authors conclude that a significant portion of the changes responsible for long-term potentiation occur in the presynaptic cell. (Consumer Summary produced by Reliance Medical Information, Inc.)

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A synaptic model of memory: long-term potentiation in the hippocampus

Article Abstract:

The best experimental model of the synaptic role in vertebrate memory and learning is long-term potentiation (LTP) of synaptic transmission in the hippocampus. Activation of the N-methyl-D-aspartate receptor complex is associated with the best understood form of LTP which also exhibits Hebbian characteristics. The persistent increase in synaptic strength required for LTP is thought to result from chemical signals produced by transduction of electrical signals at the postsynaptic membrane.

Models, Neural transmission, Synaptic transmission

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