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 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.

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.

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.

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.

Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus

1996 ◽  
Vol 75 (5) ◽  
pp. 1901-1908 ◽  
Author(s):  
M. Isokawa
Keyword(s):  
Nmda Receptor ◽  
Granule Cells ◽  
Perforant Path ◽  
High Frequency Stimulation ◽  
Patch Clamp Recording ◽  
Dentate Granule Cells ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Pilocarpine Model ◽  
Frequency Stimulation

1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy, with the use of the whole cell patch-clamp recording technique in slice preparations. 2. In the pilocarpine model, hippocampal slices were prepared from rats that were allowed to experience spontaneous seizures for 2 mo. Human hippocampal specimens were obtained from epileptic patients who underwent surgical treatment for medically intractable seizures. 3. IPSCs were generated by single perforant path stimulation and recorded at a membrane potential (Vm) of 0 mV near the reversal potential of glutamate excitatory postsynaptic currents in the voltage-clamp recording. IPSCs were pharmacologically identified as gamma-aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During low-frequency stimulation, IPSCs were not different in amplitude among non-seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure-experienced rat hippocampi, and human sclerotic hippocampi. In the last two groups of DGCs, current-clamp recordings indicated the presence of prolonged excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure-experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to recover to their original amplitude was also shortened by the application of APV. 6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory transmission may interact with GABAergic synaptic inhibition in DGCs in seizure-experienced hippocampus to transiently reduce GABA(A) receptor-channel function. Such interactions may contribute to give rise to epileptic excitation in chronically seizure-prone hippocampus.

Short- and long-term synaptic depression in rat neostriatum

1993 ◽  
Vol 70 (5) ◽  
pp. 1937-1949 ◽  
Author(s):  
D. M. Lovinger ◽  
E. C. Tyler ◽  
A. Merritt
Keyword(s):  
High Frequency ◽  
Time Course ◽  
Glutamate Release ◽  
Synaptic Depression ◽  
High Frequency Stimulation ◽  
Glutamatergic Synapses ◽  
Glutamatergic Synaptic Transmission ◽  
Frequency Stimulation ◽  
Short And Long Term

1. We have examined plasticity at glutamatergic synapses on neurons in slices of neostriatum, a forebrain area involved in movement and cognitive function. 2. High-frequency stimulation of afferent inputs to neostriatal neurons induced depression of glutamatergic synaptic transmission. Depression could be induced using either prolonged trains or short repetitive bursts of high-frequency stimulation. Depression developed within seconds after such stimulation. Responses recovered to baseline levels within 10 min in most slices but persisted for up to 60 min in others. 3. Postsynaptic passive electrical properties and the ability to elicit action potentials by postsynaptic depolarization were not altered during depression. 4. The magnitude and time course of depression was similar whether postsynaptic responses were mediated by alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or N-methyl-D-aspartate (NMDA) type glutamate receptors. Depression was not altered by antagonism of AMPA or NMDA receptors or potentiation of AMPA receptor function with aniracetam. 5. Depression was blocked by treatments that increase transmitter release including increased extracellular Ca2+, application of 4-aminopyridine, or application of phorbol ester. 6. Our findings indicate that glutamatergic synapses in neostriatum are capable of expressing a form of synaptic depression that may involve decreased glutamate release.

Synaptic depression in frog neuromuscular junction

1987 ◽  
Vol 58 (1) ◽  
pp. 230-246 ◽  
Author(s):  
M. I. Glavinovic
Keyword(s):  
Nerve Stimulation ◽  
High Frequency ◽  
Synaptic Depression ◽  
High Frequency Stimulation ◽  
Frog Neuromuscular Junction ◽  
Choline Uptake ◽  
Uptake System ◽  
End Plate ◽  
Quantal Size ◽  
Frequency Stimulation

1. The amplitudes of end-plate currents (EPCs) evoked by stimulating the nerve with frequencies ranging from 1 to 5 Hz and the amplitudes of miniature end-plate currents (MEPCs) gradually diminish if choline uptake is blocked by hemicholinium-3 (HC-3, 20 microM). This reduction of EPC amplitudes is predominantly of presynaptic origin, although an observed decrease in MEPC amplitudes suggests that some postsynaptic changes [due to direct action of HC-3 on acetylcholine (ACh) receptors or on open ACh channels] also occurs. 2. Shortening of both EPCs and MEPCs is observed during high-frequency stimulation (5 Hz) in the presence of cholinesterase inhibitor after impairment of ACh synthesis. Shortening of MEPCs probably results from a direct blocking action of HC-3 on open ACh channels, as well as from reduction in quantal size. Shortening of EPCs is more pronounced (EPCs eventually have shorter time courses than MEPCs) and usually does not result from a gradual reduction in the spatial overlap of quantal events (because of reduced quantal content) or from a diminished 'lingering ACh' (ACh that remains in the synaptic cleft between nerve impulses), but rather from a much reduced quantal size of nerve-evoked quanta. 3. It therefore appears that the quanta that are released by nerve stimulation are preferentially filled with newly synthesized ACh. In its absence nerve stimulation leads to secretion of only partially filled quanta. This occurs simultaneously with spontaneous secretion of almost normally filled quanta. Hence it seems that the quantal discharge is not strongly dependent, if at all, on its ACh content. Moreover, the correspondence between the quantal sizes of nerve-evoked and spontaneously released quanta does not remain valid during high-frequency prolonged stimulation. 4. Even with the choline uptake system intact, prolonged high-frequency stimulation leads to a gradual shortening of EPCs and, to a small extent, MEPCs. Shortening of EPCs appears to be mainly a result of a reduction of their quantal size. 5. It is estimated from the shortening of EPCs and the known EPC versus MEPC relationship that the reduction of the quantal sizes of nerve-evoked quanta probably contributes very significantly to synaptic depression that occurs during prolonged high-frequency nerve stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

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