Long-Term Potentiation (LTP) is a process, which is mainly attractive for the contemporary neuroscience. In fact, this branch of science is relatively new, but at the same time, it is essential and profound research in this field is nowadays fundamental since they contribute significantly to better understanding of many processes traditionally hidden from a naked eye but which can define the life and normal functioning of a living being.
In this respect, it is particularly noteworthy to discuss the presynaptic and postsynaptic mechanisms which are integrally involved in the maintenance of LTP, and one of the primary goals of this paper would be to find out the role of these two different processes in the maintenance of LTP across different time periods and stages.
The essence of LTP
Before discussing presynaptic and postsynaptic mechanisms and their role and impact on LTP, it is primarily necessary to briefly define LTP and find out the core of this notion because it will naturally help to better understand the role of both mechanisms in the maintenance of LTP.
First of all, it should be said that LTP is traditionally defined as the long-lasting strengthening connection between two nerve cells (Westbrook and Guthrie 1984). Naturally, such a definition seems to be quite simple, but at the same time, it is insufficient for the profound understanding of the essence of LTP. This is why it is necessary to explain the nature of this notion mostly.
In this respect, it is possible to refer to practice. To put it more precisely, it should be said that the recent experiments have revealed the fact that “a series of short, high-frequency stimulations to a nerve cell synapse can strengthen, or potentiate, the synapse for minutes to hours” (Bliss and Lomo 1973:354). In other words, it is possible to estimate that the time of the strengthening of the synapse may last from several minutes to hours under the impact of specific stimulation on a nerve cell.
However, it should be pointed out that these results were received in the temporary situation while in nature, in living cells, LTP may occur readily under the impact of natural mechanisms and can last much longer than experiments showed. Notably, it can last not only for hours but even for days, months, and years.
Probably, it is necessary to briefly the mechanism of LTP to understand better its significance and the significance of period for which it lasts in nature. So, it should be said that LTP occurs in the result of the interplay of protein kinases, phosphatases, and gene expression. Eventually, this gives rise to “synaptic plasticity and provides the foundation for highly adaptable nervous system” (Otmakhova 2000:4451). Nowadays many specialists working on neuroscientific learning theories estimate that long-term potentiations along with its opposing process, long-term depression, are the cornerstone, the cellular basis of learning and memory.
It is why it is hardly possible to underestimate the value of this process and consequently the importance of further research in this filed, which is relatively new for the modern science because LTP was initially discovered in the mammalian hippocampus by Terje Lomo in 1966. In such a way, the research in this field has lasted even for less than a half of a century, but it does not make these investigations any less significant. It is not a secret that LTP remains in the focus of attention of many specialists.
In this respect, it is necessary to point out that the modern LTP studies seek to “better understand its biology, while other research aims to develop drugs that exploit these biological mechanisms to treat neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease” (Rogan et al. 1997:607). It is why the role of research concerning LTP is vital and, in such a situation, it is particularly important to find out the role of presynaptic and postsynaptic mechanisms in the maintenance of LTP across different time periods.
The role of presynaptic and postsynaptic mechanisms in the maintenance of LTP
Speaking about the impact of presynaptic and postsynaptic mechanisms on the support of LTP, it is necessary to underline from the beginning that there are defined two main phases. The first stage is an early phase which is traditionally defined as protein-synthesis independent phase (E-LTP). Remarkably, specialists note that this step may last for a relatively short period from one to five hours. The second stage is entirely different and, to a certain extent, contrary to the previous one. This phase is traditionally defined as the late phase (L-LTP), and it is a protein synthesis-dependent phase, which lasts for quite a long time from several days to months (Otmakhova 2000).
Speaking E-LTP, as it has been just mentioned above, produces a potentiation of a few hours duration. Specialists explain that it occurs in the result of “making the postsynaptic side of the synapse more sensitive to glutamate by adding additional AMPA receptors into the postsynaptic membrane” (Weisskopf 1999:10514).
In stark contrast, L-LTP results in “a pronouncing strengthening of the postsynaptic response largely through the synthesis of new proteins” (Weisskopf 1999:10515). These proteins include glutamate receptors, for instance, AMPAR, transcription factors, and structural proteins that enhance the existing synapses and form new connections.
Furthermore, it is also necessary to point out that some of the recent researches revealed that “late LTP prompts the postsynaptic synthesis of a retrograde messenger that diffuses to the presynaptic cell increasing the probability of neurotransmitter vesicle release on subsequent stimuli” (Otmakhova 2000:4449). At the same time, it should be pointed out that the conclusions made in the results of the researchers are highly hypothetical since they are obviously insufficient and need to be continued. In fact, it is really hardly possible to estimate that the researches that have been held in recent years are absolutely reliable because firstly, certain time is needed to provide sufficient pieces of evidence of the conclusions of the researches and, secondly, it is necessary to take into consideration the conclusions and results of further researches. To prove the low reliability of the researches, it should be said that the mechanism of L-LTP, which has been just proposed above, are only weakly supported by existing data. Moreover, some specialists in the field of neurobiology even doubt the very existing of L-LTP.
Nonetheless, to support the thesis of the significance of presynaptic and postsynaptic mechanisms in the maintenance of LTP, it is necessary to draw some practical examples of recent researches. For instance, according to the analysis of Esteban (2003) the researcher, is looking for the existence and functionality and existence of presynaptic mechanisms, arguments transmitter release in hippocampal slices. The researcher presented “simulations with a quantitative model glutamatergic synaptic transmission that includes modulation of the presynaptic fusion pore, realistic cleft geometry and a distributed array of postsynaptic receptors and glutamate transporters” (Esteban 2003:122)). Eventually, he concludes that such modeling supports the idea that “changes in the dynamic of glutamate release can contribute to synaptic silencing” (Esteban 2003:218).
At the same time, the research held by Nicoll may be summoned up as follows. First of all, paired-pulse facilitation thought to be emblematic of presynaptic change, not found in perforant path, where LTP occurs. Consequently, not presynaptic and as a researcher estimates both confirmed and challenged. Furthermore, AMPA component of glutamate response increased by LTP, consistent with the postsynaptic mechanism, whereas presynaptic would have affected both. Finally, the research showed that both failure rate and coefficient of variation of release, both consistent with presynaptic effect. By the way, it is noteworthy that Nicoll remarks that “the result is robust, but not conclusive” (2003:726).
The role of tetanic stimulation and importance of multiple systems for the control of LTP
On analyzing the research concerning LTP and both presynaptic and postsynaptic mechanisms, it should be said that tetanic stimulation can also play an essential role in this process as well as multiple control for LTP, which is also of paramount importance.
Speaking about the role of tetanic stimulation, it should be pointed out that, depending on its strength, tetanic stimulation can induce LTP and it will be either of a single pathway to a synapse, or cooperatively via the weaker stimulation of many (). Such a phenomenon may be explained by the fact that there is a stimulus threshold, which has to be reached to induce LTP.
Consequently, if one pathway into a synapse is stimulated weakly, it results in insufficient postsynaptic depolarization to induce LTP. On the other hand, when “weak stimuli are applied to many pathways that converge on a single patch of the postsynaptic membrane, the individual postsynaptic depolarisations generated may collectively depolarise the postsynaptic cell enough to induce LTP cooperatively” (Otmakhova et al. 2000:4449).
As for the importance of multiple systems for the control of LTP, it should be pointed out that such operation is needed objectively to receive reliable results of the research. Otherwise, it would be hardly possible to speak about scientific reliability of any research lacking such a system. At the same time, the development of the multiple systems for the control of LTP is another problem specialists currently face researching LTP because the development of such a system is also a severe problem since the research in this field are relatively new. Consequently, there is an absolute lack of reliable multiple methods for the control of LTP, which, as it has been just mentioned above, are essential.
Thus, taking into account all above mentioned, it is possible to conclude that presynaptic and postsynaptic mechanisms can play a crucial role in the process of LTP. It should be pointed out that the presynaptic mechanism’s maintenance of LTP may be defined in temporal terms as lasting from one to five hours. As for the postsynaptic mechanism, its maintenance of LTP may be defined respectively as varying from several hours to several months. However, it should be emphasized that the data of the research are still insufficient and it is still necessary to continue the investigation in this field.
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