Synaptic Fatigue , or short-term synaptic depression, is a form that depends on the short-term synaptic plasticity activity that causes the temporary disability of the neuron to shoot and therefore emits an input signal. It is considered a form of negative feedback to physiologically control the particular form of nervous system activity.
This is due to the depletion of synaptic vesicles which cause neurotransmitters in synapses, generally produced by persistent high frequency neuronal stimulation. Neurotransmitters are released by synapses to spread signals to postsynaptic cells. It has also been hypothesized that synaptic fatigue may be a result of desensitization of postsynaptic receptors or changes in postsynaptic passive conductance, but recent evidence has shown that it is primarily a presinaptic phenomenon.
Video Synaptic fatigue
​​â € <â €
Chemical synapses allow signal transmission by presinaptic cells to release neurotransmitters to synapses to bind to receptors on postsynaptic cells. These neurotransmitters are synthesized in presinaptic cells and stored in vesicles until released. Once the neurotransmitter is released into the synaptic cleft and the signal is forwarded, the retrieval begins which is a transport protein process clearing the neurotransmitters from the synapses and recycling them to allow new signals to be multiplied. If the stimulation occurs at a sufficiently high frequency and with sufficient strength, the neurotransmitter will be released at a faster rate than the retrieval can recycle those which will eventually drain them until there are no easily removable vesicles and the signal can no longer be transmitted..
Maps Synaptic fatigue
Functional meaning
It has previously been shown that short repetitive train-action potentials lead to exponential decay of the amplitude of synaptic responses in neurons from many neural networks, especially the pontine reticular nucleus (PnC). Recent research has shown that only recurrent burst stimulation, compared with single or coupling pulse stimulation, at very high frequencies can produce SF. Some cells such as aortic baroreceptor neurons can have devastating effects including an inability to regulate aortic blood pressure if the onset of synaptic fatigue affects them. Activation of metabotropic glutamate autoreceptor in these neurons can inhibit synaptic transmission by inhibiting calcium entry, decrease exocytosis of synaptic vesicles and modulate the mechanisms that regulate the recovery of synaptic vesicles and endocytosis. These glutamate autoreceptors are able to inhibit synaptic fatigue to prevent adverse physiological consequences that can result from dysfunctional blood pressure regulation in the aorta (not true)
Synaptic recovery
When the synaptic vesicles release the neurotransmitter to the synapses that bind to the post-synaptic membrane protein to pass through the signal, the re-uptake neurotransmitter occurs to recycle the neurotransmitter in the presinaptic cell in order to be released again. Neurotransmitter vesicles are recycled through the process of endocytosis. Because each presinaptic cell can connect up to thousands of connections with other neurons, synaptic fatigue and its recovery may cause interaction with other neuronal circuits and may affect kinetics with other neuron processes. It is important that neurotransmitter recycling takes place at an effective and efficient level to prevent synaptic fatigue from the negative effects of signal transmission.
Time
Maintaining a removable vesicle pool is important in enabling constant ability to pass the physiological signals between neurons. The time taken for the neurotransmitter to be released into the synaptic cleft and then recycled back to presinaptic cells for reuse is currently not well understood. There are two models currently proposed to try to understand this process. One model predicts that the vesicle is fully fused with a presinaptic cell membrane after all its contents are emptied. Then it should take a vesicular membrane from another site that can take up to tens of seconds. The second model tries to explain this phenomenon by assuming the vesicle begins to recycle the neurotransmitter immediately after discharge, which takes less than a second to complete the endocytosis. One study showed that time varied from complete endocytosis ranging from 5.5 to 38.9 seconds. It also shows that this time is completely independent of long-term or chronic activity.
Affected cells
Synaptic fatigue can affect many synapses from different types of neurons. The existence and observation of synaptic fatigue is universally accepted, although the exact mechanisms underlying the phenomenon are not fully understood. This is generally seen in mature cells at high stimulus frequencies (& gt; 1 Hz). One specific example is that Aplysia gills retreat reflexes are caused by homosynaptic depression. Although homosynaptic and heterosynaptic depression can cause long-term depression and/or potentiation, this particular case is a short-term example of how homosynaptic depression leads to synaptic fatigue. Perforant path-granule cells (PP-GC) in the dentate gyrus of the hippocampus in adult rats have been shown to experience fatigue at lower frequencies (0.05-0.2 Hz). In PP PPs mice develop, two types of synaptic plasticity are shown to cause synaptic fatigue. Low-frequency reversible depression of presinaptic vesicle release and nonreversible depressive forms caused by AMPA silencing. The second form of plasticity disappears with the PP-GC maturation, although the reversible low-frequency depression remains unchanged.
Role in neural plasticity
Synaptic vesicles are considered to be part of three different pools: a removable swimming pool (consisting of about 5% of the total vesicles), recycling pool (about 15%), and reservoir pool (80% rest). The reserve pool seems to just start releasing the vesicles in response to intense stimuli. There have been several studies showing that spinal vesicles are rarely released in response to physiological stimuli that raise questions about its importance. This release in the vesicles, regardless of the pool where they are released, is considered a form of short-term synapsesis plasticity because it alters the functional characteristics of presinaptic cells that ultimately change the temporary burning properties. The difference between this and long-term potentiation is the fact that this phenomenon occurs only for the duration of time required to recycle and reuse neurotransmitters as opposed to it occurring over the long term as the underlying characteristics of long-term potentiation. Further research should be conducted to identify the importance of reservoir pool vesicles in presinaptic cells.
Role in CNS pathology
Synaptic fatigue has not been proven to directly cause or lead to central nervous system pathology, although the degree to which it is activated in cells has been studied as a result of pathology and certain diseases. Long-term changes in neurons or synapses, resulting in a permanent change in the excitatory nature of neurons that can cause synaptic fatigue to occur from more or less activation have the potential to cause some types of physiological abnormalities.
Alzheimer's Disease
Signs of Alzheimer's disease (AD) are cognitive impairment, amyloid peptide aggregation (A?), Neurofibriller degeneration, loss of neurons with accelerated atrophy from certain areas of the brain, and a decrease in the number of synapses in a surviving neuron. Research shows the mechanisms both pre and postcaptnaptic produce AD. One specific abnormality includes an increase in the number of APP presynaptic proteins. A study was conducted in which synaptic fatigue was compared between overexpressing APP/PS1 transgenic mice with their littermates that did not overexpress the protein. The results showed that fatigue was more pronounced in APP/PS1 mice, which showed a decrease in the number of ready-to-release presynaptic vesicles in presinaptic neurons. The conclusions of this study include synaptic fatigue which is primarily a presinaptic phenomenon and unaffected by desensitization of postsynaptic receptors, synaptic fatigue is not the result of Ca 2 ion formation in the terminal, and most importantly synaptic fatigue is an important player and can be studied when examining the causes and effects of some neurodegenerative diseases.
Depression
Antidepressants have short-term and long-term effects in depressed patients. Short-term effects are explained by the hypothesis that acute depression is caused by decreased catecholamines in the brain. Antidepressants act immediately to inhibit this decline and restore normal levels of these neurotransmitters in the brain. Under stressful conditions, vesicle eksocytosis is potentiated and catecholamine release causes presinaptic cell depression due to reduced neurotransmitters. The therapeutic dose of fluoxetine has been shown to reduce this state of neuronal fatigue by inhibiting the release of vesicles and thus preventing synaptic fatigue in hippocampal neurons. These findings suggest that fluoxetine as well as other antidepressants that act through the same mechanisms as fluoxetine improve neurorecovery and neurotransmission to reduce the risk of depression.
Questions not answered
- Although now synaptic fatigue is considered to be primarily a presinaptic phenomenon, can postcashinaps process be responsible for most of the causes currently understood for synaptic fatigue?
- Recycling of fast synaptic-vesicle membrane proteins, as demonstrated by the ability of many neurons to shoot fifty times per second, and quite specific, in which some unique membrane proteins in synaptic vesicles are specifically internalized by endocytosis. Endocytosis usually involves clathrin-coated vesicles, although non-coated clathrin vesicles may also be used. After the endocytic vesicles lose their clathrin layer, however, they usually do not coalesce with larger lower pH endosomes, as they do during endocytosis of plasma membrane proteins in other cells (see Figure 17-46). In contrast, recycled vesicles are immediately replenished with neurotransmitters.
https://www.ncbi.nlm.nih.gov/books/NBK21521/
References
Source of the article : Wikipedia
0 Comments