Activity-Dependent Release of Adenosine Contributes to Short-Term Depression at CA3-CA1 Synapses in Rat Hippocampus

2003 ◽  
Vol 89 (1) ◽  
pp. 22-26 ◽  
Author(s):  
Darrin H. Brager ◽  
Scott M. Thompson

High-frequency stimulation results in a transient, presynaptically mediated decrease in synaptic efficacy called short-term depression (STD). Stimulation of Schaffer-collateral axons at 10 Hz for 5 s resulted in approximately 75% depression of excitatory postsynaptic current (EPSC) slope recorded from CA1 cells in rat organotypic slice cultures. An adenosine A1 receptor antagonist decreased the magnitude of STD elicited with 10-Hz stimulation by approximately 30%. The A1 receptor antagonist had no effect on STD elicited with 3-Hz stimulation. The activation of A1 receptors during 10-Hz stimulation was not due to the extracellular conversion of released ATP to adenosine, because block of 5′-ectonucleotidases did not significantly affect STD. The adenosine transport inhibitor dipyridamole did not reduce STD, indicating that adenosine was not released by facilitated transport. We conclude that 10-Hz, but not 3-Hz, stimulation causes the vesicular release of adenosine and the rapid (<3 s) activation of presynaptic inhibitory A1 receptors, which account for approximately 40% of homosynaptic EPSC depression.

2012 ◽  
Vol 37 (5) ◽  
pp. 880-887 ◽  
Author(s):  
Steve Connor ◽  
Gustavo Tenorio ◽  
Michael Tom Clandinin ◽  
Yves Sauvé

While some studies on dietary supplementation with docosahexaenoic acid (DHA, 22:6n-3) have reported a beneficial effect on memory as a function of age, others have failed to find any effect. To clarify this issue, we sought to determine whether supplementing mice with a DHA-enriched diet could alter the ability of synapses to undergo activity-dependent changes in the hippocampus, a brain structure involved in forming new spatial memories. We found that DHA was increased by 29% ± 5% (mean ± SE) in the hippocampus for the supplemented (DHA+) versus nonsupplemented (control) group (n = 5 mice per group; p < 0.05). Such DHA elevation was associated with enhanced synaptic transmission (p < 0.05) as assessed by application of a high-frequency electrical stimulation protocol (100 Hz stimulation, which induced transient (<2 h) increases in synaptic strength) to slices from DHA+ (n = 4 mice) hippocampi when compared with controls (n = 4 mice). Increased synaptic responses were evident 60 min poststimulation. These results suggest that dietary DHA supplementation facilitates synaptic plasticity following brief high-frequency stimulation. This increase in synaptic transmission might provide a physiological correlation for the improved spatial learning and memory observed following DHA supplementation.


1998 ◽  
Vol 79 (3) ◽  
pp. 1277-1285 ◽  
Author(s):  
Andrew A. V. Hill ◽  
Ping Jin

Hill, Andrew A. V. and Ping Jin. Regulation of synaptic depression rates in the cricket cercal sensory system. J. Neurophysiol. 79: 1277–1285, 1998. To assess the roles of pre- and postsynaptic mechanisms in the regulation of depression, short-term synaptic depression was characterized at the synapses between sensory neurons and two interneurons in the cricket cercal sensory system. Changes in excitatory postsynaptic potential (EPSP) amplitude with repetitive stimulation at 5 and 20 Hz were quantified and fitted to the depletion model of transmitter release. The depression rates of different sensory neuron synapses on a single interneuron varied with the age of the sensory neurons such that old sensory neuron synapses depressed faster than young synapses. Although all synapses showed depression, short-term facilitation was selectively expressed only at sensory neuron synapses on one interneuron, the medial giant interneuron (MGI). These synapses showed concurrent facilitation and depression with high-frequency stimulation (100 Hz), whereas the synapses on another interneuron, 10-3, showed only depression at all stimulus frequencies. A previous study showed that the ability of a synapse to facilitate is correlated with the identity of the postsynaptic neuron. The present results indicate that depression and facilitation are regulated independently. Depression is regulated presynaptically in a manner related to sensory neuron age; whereas, facilitation is regulated by the postsynaptic target.


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.


2014 ◽  
Vol 111 (4) ◽  
pp. 888-895 ◽  
Author(s):  
Michael Ryan ◽  
Jaime Kaminer ◽  
Patricia Enmore ◽  
Craig Evinger

Reflex blinks provide a model system for investigating motor learning in normal and pathological states. We investigated whether high-frequency stimulation (HFS) of the supraorbital branch of the trigeminal nerve before the R2 blink component (HFS-B) decreases reflex blink gain in alert rats. As with humans (Mao JB, Evinger C. J Neurosci 21: RC151, 2001), HFS-B significantly reduced blink size in the first hour after treatment for rats. Repeated days of HFS-B treatment produced long-term depression of blink circuits. Blink gain decreased exponentially across days, indicating a long-term depression of blink circuits. Additionally, the HFS-B protocol became more effective at depressing blink amplitude across days of treatment. This depression was not habituation, because neither long- nor short-term blink changes occurred when HFS was presented after the R2. To investigate whether gain modifications produced by HFS-B involved cerebellar networks, we trained rats in a delay eyelid conditioning paradigm using HFS-B as the unconditioned stimulus and a tone as the conditioned stimulus. As HFS-B depresses blink circuits and delay conditioning enhances blink circuit activity, occlusion should occur if they share neural networks. Rats acquiring robust eyelid conditioning did not exhibit decreases in blink gain, whereas rats developing low levels of eyelid conditioning exhibited weak, short-term reductions in blink gain. These results suggested that delay eyelid conditioning and long-term HFS-B utilize some of the same cerebellar circuits. The ability of repeated HFS-B treatment to depress trigeminal blink circuit activity long term implied that it may be a useful protocol to reduce hyperexcitable blink circuits that underlie diseases like benign essential blepharospasm.


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.


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