scholarly journals Tissue-specific dynamin-1 deletion at the calyx of Held decreases short-term depression through a mechanism distinct from vesicle resupply

2016 ◽  
Vol 113 (22) ◽  
pp. E3150-E3158 ◽  
Author(s):  
Satyajit Mahapatra ◽  
Fan Fan ◽  
Xuelin Lou
Keyword(s):  
Steady State ◽  
Synaptic Vesicle ◽  
High Frequency ◽  
Synaptic Depression ◽  
Conditional Knockout ◽  
High Frequency Stimulation ◽  
Latrunculin B ◽  
Short Term ◽  
Tissue Specific ◽  
Frequency Stimulation

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.

Regulation of Synaptic Depression Rates in the Cricket Cercal Sensory System

1998 ◽  
Vol 79 (3) ◽  
pp. 1277-1285 ◽  
Author(s):  
Andrew A. V. Hill ◽  
Ping Jin
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
High Frequency ◽  
Sensory System ◽  
Synaptic Depression ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Short Term ◽  
Frequency Stimulation ◽  
Postsynaptic Target

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.

scholarly journals Nonequivalent release sites govern synaptic depression

2015 ◽  
Vol 113 (3) ◽  
pp. E378-E386 ◽  
Author(s):  
Hua Wen ◽  
Matthew J. McGinley ◽  
Gail Mandel ◽  
Paul Brehm
Keyword(s):  
Steady State ◽  
Release Site ◽  
Synaptic Depression ◽  
Nonlinear Dependence ◽  
High Frequency Stimulation ◽  
Patch Clamp Recording ◽  
Highly Nonlinear ◽  
Frequency Stimulation ◽  
State Transmission ◽  
State Depression

Synaptic depression is prominent among synapses, but the underlying mechanisms remain uncertain. Here, we use paired patch clamp recording to study neuromuscular transmission between the caudal primary motor neuron and target skeletal muscle in zebrafish. This synapse has an unusually low number of release sites, all with high probabilities of release in response to low-frequency stimulation. During high-frequency stimulation, the synapse undergoes short-term depression and reaches steady-state levels of transmission that sustain the swimming behavior. To determine the release parameters underlying this steady state, we applied variance analysis. Our analysis revealed two functionally distinct subclasses of release sites differing by over 60-fold in rates of vesicle reloading. A slow reloading class requires seconds to recover and contributes to depression onset but not the steady-state transmission. By contrast, a fast reloading class recovers within tens of milliseconds and is solely responsible for steady-state transmission. Thus, in contrast to most current models that assign levels of steady-state depression to vesicle availability, our findings instead assign this function to nonuniform release site kinetics. The duality of active-site properties accounts for the highly nonlinear dependence of steady-state depression levels on frequency.

scholarly journals Distinct Temporal Filters In Mitral Cells And External Tufted Cells Of The Olfactory Bulb

2017 ◽  
Author(s):  
Christopher E. Vaaga ◽  
Gary L. Westbrook
Keyword(s):  
Olfactory Bulb ◽  
High Frequency ◽  
Synaptic Depression ◽  
High Frequency Stimulation ◽  
Mitral Cells ◽  
Release Probability ◽  
High Release ◽  
Frequency Stimulation ◽  
Tufted Cells ◽  
Synaptic Dynamics

Short-term synaptic plasticity is a critical regulator of neural circuits, and largely determines how information is temporally processed. In the olfactory bulb, afferent olfactory receptor neurons respond to increasing concentrations of odorants with barrages of action potentials, and their terminals have an extraordinarily high release probability (Sicard, 1986; Murphy et al., 2004). These features suggest that during naturalistic stimuli, afferent input to the olfactory bulb is subject to strong synaptic depression, presumably truncating the postsynaptic response to afferent stimuli. To examine this issue, we used single glomerular stimulation in mouse olfactory bulb slices to measure the synaptic dynamics of afferent-evoked input at physiological stimulus frequencies. In cell-attached recordings, mitral cells responded to high frequency stimulation with sustained responses, whereas external tufted cells responded transiently. Consistent with previous reports (Murphy et al., 2004), olfactory nerve terminals onto both cell types had a high release probability (0.7), from a single pool of slowly recycling vesicles, indicating that the distinct responses of mitral and external tufted cells to high frequency stimulation did not originate presyaptically. Rather, distinct temporal response profiles in mitral cells and external tufted cells could be attributed to slow dendrodendritic responses in mitral cells, as blocking this slow current in mitral cells converted mitral cell responses to a transient response profile, typical of external tufted cells. Our results suggest that despite strong axodendritic synaptic depression, the balance of axodendritic and dendrodendritic circuitry in external tufted cells and mitral cells, respectively, tunes the postsynaptic responses to high frequency, naturalistic stimulation.

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
Keyword(s):  
Receptor Antagonist ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
Short Term ◽  
Transport Inhibitor ◽  
Vesicular Release ◽  
Organotypic Slice Cultures ◽  
Adenosine Transport ◽  
Frequency Stimulation ◽  
Activity Dependent

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.

scholarly journals Trigeminal high-frequency stimulation produces short- and long-term modification of reflex blink gain

2014 ◽  
Vol 111 (4) ◽  
pp. 888-895 ◽  
Author(s):  
Michael Ryan ◽  
Jaime Kaminer ◽  
Patricia Enmore ◽  
Craig Evinger
Keyword(s):  
High Frequency ◽  
Eyelid Conditioning ◽  
High Frequency Stimulation ◽  
Short Term ◽  
Long Term Depression ◽  
Delay Conditioning ◽  
Essential Blepharospasm ◽  
Reflex Blink ◽  
Frequency Stimulation

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.

Steady State Average Evoked Potentials as a Measure of Tracking Difficulty

1980 ◽  
Vol 24 (1) ◽  
pp. 678-680
Author(s):  
Glenn F. Wilson
Keyword(s):  
Steady State ◽  
Evoked Potentials ◽  
High Frequency ◽  
Sine Wave ◽  
Tracking Task ◽  
High Frequency Stimulation ◽  
Phase Lag ◽  
Frequency Stimulation ◽  
Modulated Light ◽  
State Average

The utility of steady state average evoked potentials (AEPs) to measure the difficulty of a tracking task will be reported. Medium (14 Hz) and high (50–56 Hz) frequency sine wave modulated light was used to evoke steady state AEPs while subjects performed a tracking task. Three levels of difficulty, based upon each subject's ability, were used in the single axis visual tracking task. The phase lag between stimulus input and the AEP waveform was found to be significantly related to task difficulty. Increasing difficulty levels were associated with greater amounts of phase lag of the AEPs during the high frequency stimulation. Neither the phase lag nor the amplitude of the medium frequency AEPs were significantly affected by the level of tracking difficulty. Each subject was found to have one particular frequency of stimulation in the high range which produced an enhanced AEP amplitude. This suggests that researchers using high frequency stimulation with sine wave modulated light should test each subject to find the frequency which produces the maximal amplitude.

Depression of postsynaptic potentials by high-frequency stimulation in embryonic motoneurons grown in spinal cord slice cultures

1992 ◽  
Vol 68 (5) ◽  
pp. 1793-1803 ◽  
Author(s):  
J. Streit ◽  
C. Luscher ◽  
H. R. Luscher
Keyword(s):  
Spinal Cord ◽  
Dorsal Root Ganglia ◽  
High Frequency ◽  
Dorsal Root ◽  
Input Resistance ◽  
Synaptic Depression ◽  
High Frequency Stimulation ◽  
Postsynaptic Potentials ◽  
Wide Range ◽  
Frequency Stimulation

1. In embryonic cocultures of spinal cord, dorsal root ganglia, and muscle, excitatory postsynaptic potentials (EPSPs) were recorded in motoneurons during focal electrical stimulation of the dorsal root ganglia or the spinal cord. 2. EPSPs were depressed in amplitude at high-frequency stimulation relative to a control frequency of 0.5 Hz by 47 and 75% at 5 and 10 Hz, respectively. This was true for composite EPSPs and unitary EPSPs. 3. The depression showed a wide range of variability between individual experiments. The degree of depression at 5 Hz was negatively correlated to the rate of spontaneous excitatory input the motoneurons received. There was no correlation to the soma size, the average amplitude of the EPSPs, the rheobase, or the input resistance of the motoneurons. 4. An increase in latency of EPSPs was observed concomitant with or preceding the synaptic depression in most experiments. Total transmission failures, which were absent at low-frequency stimulation, appeared during depression. 5. Large incremental steps in amplitude could be seen during depression, suggesting that several release sites were switched off and on together. 6. Decreasing the extracellular calcium concentration from 5 to 1 mM led to a decrease in the frequency sensitivity of the synaptic efficacy and to a decrease of the EPSP amplitude and latency. 7. Measurements of the antidromic conduction of action potentials evoked in the axons and recorded in the somata of dorsal root ganglion cells revealed an increase in latency and the appearance of conduction failures at stimulation frequencies of 1-10 Hz. The frequency modulation of conduction was decreased in 1 mM compared with 5 mM external calcium. 8. Together these findings suggest that conduction failures in the presynaptic axons contribute to the synaptic depression of EPSPs in embryonic motoneurons.

Developmental Changes in Short-Term Synaptic Depression in the Neonatal Mouse Spinal Cord

2002 ◽  
Vol 88 (6) ◽  
pp. 3218-3231 ◽  
Author(s):  
Yan Li ◽  
R. E. Burke
Keyword(s):  
Steady State ◽  
High Frequency ◽  
Transmitter Release ◽  
Synaptic Depression ◽  
The Other ◽  
Postnatal Life ◽  
Short Term ◽  
Constant Frequency ◽  
Paired Pulse ◽  
State Depression

We examined age-dependent changes in short-term synaptic depression of monosynaptic excitatory postsynaptic potentials (EPSPs) recorded in lumbar motoneurons in hemisected spinal cords of neonatal Swiss-Webster mice between postnatal day 2 (P2) and 12 (P12). We used four paradigms that sample the input-output dependence on stimulation history in different but complementary ways: 1) paired-pulse depression; 2) steady-state depression during constant frequency trains; 3) modulation during irregular stimulation sequences; and 4) recovery after high-frequency conditioning trains. Paired-pulse synaptic depression declined more than steady-state depression during 10-pulse trains at frequencies from 0.125 to 8 Hz in this age range. Depression during sequences of irregular stimulations that more closely mimic physiological activation also declined with postnatal age. On the other hand, the overall rate of synaptic recovery after a 4-Hz conditioning train exhibited surprisingly little change between P2 and P12. Control experiments indicated that these observations depend primarily, if not exclusively, on changes in presynaptic transmitter release. The data were examined using quantitative models that incorporate factors that have been suggested to exist at more specialized central synapses. The model that best predicted the observations included two presynaptic compartments that are depleted during activation, plus two superimposed processes that enhance transmitter release by different mechanisms. One of the latter produced rapidly-decaying enhancement of transmitter release fraction. The other mechanism indirectly enhanced the rate of renewal of one of the depleted presynaptic compartments. This model successfully predicted the constant frequency and irregular sequence data from all age groups, as well as the recovery curves following short, high-frequency tetani. The results suggest that a reduction in release fraction accounts for much of the decline in synaptic depression during early postnatal development, although changes in both enhancement processes also contribute. The time constants of resource renewal showed surprisingly little change through the first 12 days of postnatal life.

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
Keyword(s):  
Synaptic Vesicle ◽  
High Frequency ◽  
Transmitter Release ◽  
Synaptic Vesicles ◽  
High Frequency Stimulation ◽  
Vesicle Pools ◽  
Bivalent Cations ◽  
Frequency Stimulation ◽  
Nerve Muscle ◽  
Vesicle Pool

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.

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