The Same Synaptic Vesicles Originate Synchronous and Asynchronous Transmitter Release

Acta Naturae ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 81-88 ◽  
Author(s):  
P. N. Grigoryev ◽  
A. L. Zefirov

Transmitter release and synaptic vesicle exo- and endocytosis during high-frequency stimulation (20 pulses/s) in the extracellular presence of different bivalent cations (Ca2+, Sr2+ or Ba2+) were studied in frog cutaneous pectoris nerve-muscle preparations. It was shown in electrophysiological experiments that almost only synchronous transmitter release was registered in a Ca2+-containing solution; a high intensity of both synchronous and asynchronous transmitter release was registered in a Sr2+-containing solution, and asynchronous transmitter release almost only was observed in a Ba2+-containing solution. It was shown in experiments with a FM 1-43 fluorescent dye that the synaptic vesicles that undergo exocytosis-endocytosis during synchronous transmitter release (Ca-solutions) are able to participate in asynchronous exocytosis in Ba-solutions. The vesicles that had participated in the asynchronous transmitter release (Ba-solutions) could subsequently participate in a synchronous release (Ca-solutions). It was shown in experiments with isolated staining of recycling and reserve synaptic vesicle pools that both types of evoked transmitter release originate from the same synaptic vesicle pool.

2016 ◽  
Vol 113 (22) ◽  
pp. E3150-E3158 ◽  
Author(s):  
Satyajit Mahapatra ◽  
Fan Fan ◽  
Xuelin Lou

Dynamin is a large GTPase with a crucial role in synaptic vesicle regeneration. Acute dynamin inhibition impairs neurotransmitter release, in agreement with the protein’s established role in vesicle resupply. Here, using tissue-specific dynamin-1 knockout [conditional knockout (cKO)] mice at a fast central synapse that releases neurotransmitter at high rates, we report that dynamin-1 deletion unexpectedly leads to enhanced steady-state neurotransmission and consequently less synaptic depression during brief periods of high-frequency stimulation. These changes are also accompanied by increased transmission failures. Interestingly, synaptic vesicle resupply and several other synaptic properties remain intact, including basal neurotransmission, presynaptic Ca2+ influx, initial release probability, and postsynaptic receptor saturation and desensitization. However, acute application of Latrunculin B, a reagent known to induce actin depolymerization and impair bulk and ultrafast endocytosis, has a stronger effect on steady-state depression in cKO than in control and brings the depression down to a control level. The slow phase of presynaptic capacitance decay following strong stimulation is impaired in cKO; the rapid capacitance changes immediately after strong depolarization are also different between control and cKO and sensitive to Latrunculin B. These data raise the possibility that, in addition to its established function in regenerating synaptic vesicles, the endocytosis protein dynamin-1 may have an impact on short-term synaptic depression. This role comes into play primarily during brief high-frequency stimulation.


2004 ◽  
Vol 91 (4) ◽  
pp. 1500-1509 ◽  
Author(s):  
Yali Zhao ◽  
Marc Klein

Synaptic transmission at the sensory neuron-motor neuron synapses of Aplysia, like transmission at many synapses of both vertebrates and invertebrates, is increased after a short burst of high-frequency stimulation (HFS), a phenomenon known as posttetanic potentiation (PTP). PTP is generally attributable to an increase in transmitter release from presynaptic neurons. We investigated whether changes in the readily releasable pool of transmitter (RRP) contribute to the potentiation that follows HFS. We compared the changes in excitatory postsynaptic potentials (EPSPs) evoked with action potentials to changes in the RRP as estimated from the asynchronous transmitter release elicited by a hypertonic solution. The changes in the EPSP were correlated with changes in the RRP, but the changes matched quantitatively only at connections whose initial synaptic strength was greater than the median for all experiments. At weaker connections, the increase in the RRP was insufficient to account for PTP. Weaker connections initially released a smaller fraction of the RRP with each EPSP than stronger ones, and this fraction increased at weaker connections after HFS. Moreover, the initial transmitter release in response to the hypertonic solution was accelerated after HFS, indicating that the increase in the efficacy of release was not restricted to excitation-secretion coupling. Modulation of the RRP and of the efficacy of release thus both contribute to the enhancement of transmitter release by HFS.


2010 ◽  
Vol 136 (3) ◽  
pp. 259-272 ◽  
Author(s):  
Jae Sung Lee ◽  
Won-Kyung Ho ◽  
Suk-Ho Lee

Post-tetanic potentiation (PTP) at the calyx of Held synapse is caused by increases not only in release probability (Pr) but also in the readily releasable pool size estimated from a cumulative plot of excitatory post-synaptic current amplitudes (RRPcum), which contribute to the augmentation phase and the late phase of PTP, respectively. The vesicle pool dynamics underlying the latter has not been investigated, because PTP is abolished by presynaptic whole-cell patch clamp. We found that supplement of recombinant calmodulin to the presynaptic pipette solution rescued the increase in the RRPcum after high-frequency stimulation (100 Hz for 4-s duration, HFS), but not the increase in Pr. Release-competent synaptic vesicles (SVs) are heterogeneous in their releasing kinetics. To investigate post-tetanic changes of fast and slowly releasing SV pool (FRP and SRP) sizes, we estimated quantal release rates before and 40 s after HFS using the deconvolution method. After HFS, the FRP size increased by 19.1% and the SRP size decreased by 25.4%, whereas the sum of FRP and SRP sizes did not increase. Similar changes in the RRP were induced by a single long depolarizing pulse (100 ms). The post-tetanic complementary changes of FRP and SRP sizes were abolished by inhibitors of myosin II or myosin light chain kinase. The post-tetanic increase in the FRP size coupled to a decrease in the SRP size provides the first line of evidence for the idea that a slowly releasing SV can be converted to a fast releasing one.


2020 ◽  
Vol 44 (3) ◽  
pp. 241-249
Author(s):  
Yoshiaki Omura

While a visiting Professor at the University of Paris, VI (formerly Sorvonne) more than 40 years ago, the Author became very good friends with Dr. Paul Nogier who periodically gave seminars and workshops in Paris. After the author diagnosed his cervical problem & offered him simple help, Dr. Nogier asked the Author to present lectures and demonstrations on the effects of ear stimulation, namely the effects of acupuncture & electrical stimulation of the ear lobules. It is only now, in 2019 that we have discovered 2–5 minute high frequency stimulation of the ear lobule inhibits cancer activity for 1– 4 hours post stimulation. Although the procedure is extremely simple. First take optimal dose of Vitamin D3, which has the most essential 10 unique beneficial factors required for every human cell activity. Next, apply high frequency stimulation to ear lobule while the worst ear lobule is held by all fingers with vibrator directly touching the surface of the worst ear lobule, preferably after patient repeatedly takes optimal dose of Vitamin D3. When the worst ear lobule is held between thumb & index fingers and applying mechanical stimulation of 250 ~ 500 mechanical vibration/second for 2 ~ 5 minutes using an electrical vibrator, there is rapid disappearance of cancer activity in both the brain and rest of the body for short time duration 1 ~ 4 hours. The effect often increases by additional pressure by holding fingers. As of May 2019, the Author found that many people from various regions of the world developed early stages of multiple cancers. For evaluation of this study, U. S. patented Bi-Digital O-Ring Test (BDORT) was used which was developed by the Author while doing his Graduate experimental physics research at Colombia University. BDORT was found to be most essential for determining the beneficial effects as well as harmful effects of any substance or treatment. Using BDORT, Author was the first to recognize severe increasing mid-backache was an early sign of pancreatic cancer of President of New York State Board of Medicine after top pain specialists failed to detect the cause after 3 years of effort, while the BDORT showed early stages of cancer whereas conventional X-Ray of the pancreas did not show any cancer image until 2 months after Author detected with BDORT. For example, the optimal dose of the banana is usually about 2.0 - 2.5 millimeters cross section of the banana. A whole banana is more than 50 ~ 100 times the optimal dose. Any substance eaten in more than 25 times of its optimal dose becomes highly toxic and creates DNA mutations which can cause multiple malignancies in the presence of strong electro-magnetic field. With standard medication given by doctor, patients often become sick and they are unable to reduce body weight, unless medication is reduced or completely stopped. When the amount of zinc is very high, DNA often becomes unstable and multiple cancers can grow rapidly in the presence of strong electromagnetic field. Large amount of Vitamin C from regular orange or orange juice inhibit the most important Vitamin D3 effects. At least 3 kinds of low Vitamin C oranges will not inhibit Vitamin D3. Since B12 particularly methyl cobalamin which is a red small tablet is known to improve brain circulation very significantly we examined its effect within 20 seconds of oral intake we found the following very significant changes. Acetylcholine in both sides of the brain often increases over 4,500 ng. Longevity gene Sirtuin 1 level increases significantly for short time of few hours. Thymosin α1 and Thymosinβ4 both increase to over 1500 ng from 20 ng or less.


1957 ◽  
Vol 40 (3) ◽  
pp. 435-450 ◽  
Author(s):  
David P. C. Lloyd

An assemblage of individual motoneurons constituting a synthetic motoneuron pool has been studied from the standpoint of relating monosynaptic reflex responses to frequency of afferent stimulation. Intensity of low frequency depression is not a simple function of transmitter potentiality. As frequency of stimulation increases from 3 per minute to 10 per second, low frequency depression increases in magnitude. Between 10 and approximately 60 per second low frequency depression apparently diminishes and subnormality becomes a factor in causing depression. At frequencies above 60 per second temporal summation occurs, but subnormality limits the degree of response attainable by summation. At low stimulation frequencies rhythm is determined by stimulation frequency. Interruptions of rhythmic firing depend solely upon temporal fluctuation of excitability. At high frequency of stimulation rhythm is determined by subnormality rather than inherent rhythmicity, and excitability fluctuation leads to instability of response rhythm. In short, whatever the stimulation frequency, random excitability fluctuation is the factor disrupting rhythmic response. Monosynaptic reflex response latency is stable during high frequency stimulation as it is in low frequency stimulation provided a significant extrinsic source of random bombardment is not present. In the presence of powerful random bombardment discharge may become random with respect to monosynaptic afferent excitation provided the latter is feeble. When this occurs it does so equally at low frequency and high frequency. Thus temporal summation is not a necessary factor. There is, then, no remaining evidence to suggest that the agency for temporal summation in the monosynaptic system becomes a transmitting agency in its own right.


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