scholarly journals Glycinergic Transmission in the Presence and Absence of Functional GlyT2: Lessons From the Auditory Brainstem

2021 ◽  
Vol 12 ◽  
Author(s):  
Sina E. Brill ◽  
Ayse Maraslioglu ◽  
Catharina Kurz ◽  
Florian Kramer ◽  
Martin F. Fuhr ◽  
...  
Keyword(s):  
Synaptic Cleft ◽  
Auditory Brainstem ◽  
Dominant Factor ◽  
High Frequency Stimulation ◽  
High Fidelity ◽  
Readily Releasable Pool ◽  
Medial Nucleus ◽  
Frequency Stimulation ◽  
Replenishment Kinetics

Synaptic transmission is controlled by re-uptake systems that reduce transmitter concentrations in the synaptic cleft and recycle the transmitter into presynaptic terminals. The re-uptake systems are thought to ensure cytosolic concentrations in the terminals that are sufficient for reloading empty synaptic vesicles (SVs). Genetic deletion of glycine transporter 2 (GlyT2) results in severely disrupted inhibitory neurotransmission and ultimately to death. Here we investigated the role of GlyT2 at inhibitory glycinergic synapses in the mammalian auditory brainstem. These synapses are tuned for resilience, reliability, and precision, even during sustained high-frequency stimulation when endocytosis and refilling of SVs probably contribute substantially to efficient replenishment of the readily releasable pool (RRP). Such robust synapses are formed between MNTB and LSO neurons (medial nucleus of the trapezoid body, lateral superior olive). By means of patch-clamp recordings, we assessed the synaptic performance in controls, in GlyT2 knockout mice (KOs), and upon acute pharmacological GlyT2 blockade. Via computational modeling, we calculated the reoccupation rate of empty release sites and RRP replenishment kinetics during 60-s challenge and 60-s recovery periods. Control MNTB-LSO inputs maintained high fidelity neurotransmission at 50 Hz for 60 s and recovered very efficiently from synaptic depression. During 'marathon-experiments' (30,600 stimuli in 20 min), RRP replenishment accumulated to 1,260-fold. In contrast, KO inputs featured severe impairments. For example, the input number was reduced to ~1 (vs. ~4 in controls), implying massive functional degeneration of the MNTB-LSO microcircuit and a role of GlyT2 during synapse maturation. Surprisingly, neurotransmission did not collapse completely in KOs as inputs still replenished their small RRP 80-fold upon 50 Hz | 60 s challenge. However, they totally failed to do so for extended periods. Upon acute pharmacological GlyT2 inactivation, synaptic performance remained robust, in stark contrast to KOs. RRP replenishment was 865-fold in marathon-experiments, only ~1/3 lower than in controls. Collectively, our empirical and modeling results demonstrate that GlyT2 re-uptake activity is not the dominant factor in the SV recycling pathway that imparts indefatigability to MNTB-LSO synapses. We postulate that additional glycine sources, possibly the antiporter Asc-1, contribute to RRP replenishment at these high-fidelity brainstem synapses.

Role of fascia in maintenance of muscle tension and pressure

1981 ◽  
Vol 51 (2) ◽  
pp. 317-320 ◽  
Author(s):  
S. R. Garfin ◽  
C. M. Tipton ◽  
S. J. Mubarak ◽  
S. L. Woo ◽  
A. R. Hargens ◽  
...  
Keyword(s):  
High Frequency ◽  
Muscle Tension ◽  
Fluid Pressure ◽  
Low Frequency ◽  
Testing Procedure ◽  
Force Transducer ◽  
High Frequency Stimulation ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation

The effect of fasciotomy on muscle tension (measured by a force transducer attached to the tendon) and interstitial fluid pressure (measured by Wick catheters in the muscle belly) was studied in the anterolateral compartments of 13 dog hindlimbs. Muscle tension and pressure were monitored in the tibialis cranialis muscle after low- and high-frequency stimulation of the peroneal nerve to produce twitch- and tetanic-type contractions. Fasciotomy decreased muscle force during the low-frequency stimulation by 16% (35.3 +/- 4.9 to 28.4 +/- 3.9 N) and during the high-frequency stimulation by 10% (60.8 %/- 4.9 to 54.8 +/- 3.9 N). Muscle pressure decreased 50% after fasciotomy under both conditions, 15 +/- 2 to 6 +/- 1 mmHg and 84 +/- 17 to 41 +/- 8 mmHg), respectively. Repeated functional evaluations during the testing procedure indicated that muscle fatigue was not a major factor in these results. It was concluded that fascia is important in the development of muscle tension and changes in interstitial pressure. Furthermore, the results raised questions concerning the merits of performing a fasciotomy for athletes with a compartment syndrome.

Rescue of motoneuron and muscle afferent function in cats by regeneration into skin. II. Ia-motoneuron synapse

1995 ◽  
Vol 73 (2) ◽  
pp. 662-673 ◽  
Author(s):  
L. M. Mendell ◽  
J. S. Taylor ◽  
R. D. Johnson ◽  
J. B. Munson
Keyword(s):  
High Frequency ◽  
Muscle Afferents ◽  
Medial Gastrocnemius ◽  
High Frequency Stimulation ◽  
Lateral Gastrocnemius ◽  
Essentially Normal ◽  
Muscle Afferent ◽  
Muscle Nerve ◽  
Frequency Stimulation

1. In this study we describe application of high-frequency stimulation to the group Ia afferent-to-motoneuron synapse of cats to determine the extent to which regeneration of axotomized muscle afferents and motoneurons into skin or into muscle rescues their ability to generate excitatory postsynaptic potentials (EPSPs). 2. The medial gastrocnemius (MG) muscle nerve was transected and 1) left chronically axotomized, 2) cross-united to the caudal cutaneous sural (CCS) nerve, or 3) self-united. The ability of the operated MG muscle afferents to generate EPSPs in normal lateral gastrocnemius-soleus (LGS) motoneurons and of normal LGS muscle afferents to generate EPSPs in the operated MG motoneurons was tested 5 wk-30 mo later. 3. EPSPs were generated by bursts of 32 shocks at 167 Hz and averaged in register. In normal cats, EPSP amplitude decreased (negative modulation) during these bursts in type S motoneurons and could increase or decrease in type F motoneurons (positive or negative modulation). 4. After axotomy, EPSPs generated both in axotomized motoneurons and by axotomized afferents showed only negative modulation during the burst, and the negative modulation was much greater than in normal animals. Regeneration of the muscle nerve into skin significantly decreased the negative modulation relative to axotomy. Regeneration of the muscle nerve into muscle restored the EPSP modulation behaviors even more, to essentially normal values. 5. We conclude that the ability of muscle afferents to generate EPSPs in motoneurons in response to high-frequency stimulation, and the ability of motoneurons to express those EPSPs, are both influenced by the target innervated by those neurons. Synaptic efficacy is severely reduced by target deprivation (axotomy), partially rescued by cross-regeneration into skin, and rescued virtually completely by regeneration into the native muscle. We speculate on the role of target-derived neurotrophins in these effects.

Differential Effects of SNAP-25 Deletion on Ca2+-Dependent and Ca2+-Independent Neurotransmission

2007 ◽  
Vol 98 (2) ◽  
pp. 794-806 ◽  
Author(s):  
Peter Bronk ◽  
Ferenc Deák ◽  
Michael C. Wilson ◽  
Xinran Liu ◽  
Thomas C. Südhof ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
High Frequency Stimulation ◽  
Neuronal Cultures ◽  
Inhibitory Neurotransmitter ◽  
Calcium Dependent ◽  
Receptor Complexes ◽  
Readily Releasable Pool ◽  
Protein Receptor ◽  
Frequency Stimulation ◽  
Hypertonic Stimulation

At the synapse, SNAP-25, along with syntaxin/HPC-1 and synaptobrevin/VAMP, forms SNARE N-ethylmaleimide-sensitive factor [soluble (NSF) attachment protein receptor] complexes that are thought to catalyze membrane fusion. Results from neuronal cultures of synaptobrevin-2 knockout (KO) mice showed that loss of synaptobrevin has a more severe effect on calcium-evoked release than on spontaneous release or on release evoked by hypertonicity. In this study, we recorded neurotransmitter release from neuronal cultures of SNAP-25 KO mice to determine whether they share this property. In neurons lacking SNAP-25, as those deficient in synaptobrevin-2, we found that ∼10–12% of calcium-independent excitatory and inhibitory neurotransmitter release persisted. However, in contrast to synaptobrevin-2 knockouts, this remaining readily releasable pool in SNAP-25-deficient synapses was virtually insensitive to calcium-dependent–evoked stimulation. Although field stimulation reliably evoked neurotransmitter release in synaptobrevin-2 KO neurons, responses were rare in neurons lacking SNAP-25, and unlike synaptobrevin-2–deficient synapses, SNAP-25–deficient synapses did not exhibit facilitation of release during high-frequency stimulation. This severe loss of evoked exocytosis was matched by a reduction, but not a complete loss, of endocytosis during evoked stimulation. Moreover, synaptic vesicle turnover probed by FM-dye uptake and release during hypertonic stimulation was relatively unaffected by the absence of SNAP-25. This last difference indicates that in contrast to synaptobrevin, SNAP-25 does not directly function in endocytosis. Together, these results suggest that SNAP-25 has a more significant role in calcium-secretion coupling than synaptobrevin-2.

Modulation of synaptic transmission at Ia-afferent fiber connections on motoneurons during high-frequency stimulation: role of postsynaptic target

1991 ◽  
Vol 65 (3) ◽  
pp. 590-597 ◽  
Author(s):  
H. R. Koerber ◽  
L. M. Mendell
Keyword(s):  
High Frequency ◽  
Afferent Fiber ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Epsp Amplitude ◽  
Marked Variability ◽  
Frequency Stimulation ◽  
Frequency Burst ◽  
Stimulation Of

1. High-frequency stimulation of single group Ia-fibers results in modulation of excitatory postsynaptic potential (EPSP) amplitude recorded in target motoneurons. This can be either positive (EPSP amplitude increases in response to successive stimuli in the high-frequency burst) or negative (decrease in EPSP amplitude). We have investigated whether the magnitude of modulation is associated with the stimulated afferent, the responding motoneuron, or the amplitude of the EPSP. 2. In agreement with previous findings, we found that positive modulation tends to occur at connections generating small EPSPs and negative modulation, at those producing large EPSPs. Because large EPSPs generally are evoked in motoneurons with low values of rheobase, we found, as anticipated, that connections on low rheobase motoneurons are prone to negative modulation during high-frequency stimulation, whereas those on high rheobase motoneurons (which tend to generate small EPSPs) are prone to positive modulation. 3. In experiments where the projection of multiple afferents to a single motoneuron was studied, we found that amplitude modulation was similar despite differences in EPSP amplitude. Thus in a given motoneuron there is no relationship between modulation and amplitude, in contrast to the existence of such a relationship in the population of connections as a whole. 4. In the converse experiments where the projection of single afferents to multiple motoneurons was studied, we found marked variability in the modulation patterns with clear indications that amplitude and modulation are correlated as in the entire population of Ia/motoneuron connections. 5. We tested the constancy of modulation patterns evoked in a given motoneuron by comparing the modulation patterns evoked in motoneurons by single fibers, and by stimulation of the heteronymous nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Multiple Sources of Cholinergic Input to the Superior Olivary Complex

2021 ◽  
Vol 15 ◽  
Author(s):  
Nichole L. Beebe ◽  
Chao Zhang ◽  
R. Michael Burger ◽  
Brett R. Schofield
Keyword(s):  
Auditory System ◽  
Cholinergic Neurons ◽  
Auditory Brainstem ◽  
Cholinergic Innervation ◽  
Superior Olivary Complex ◽  
Multiple Sources ◽  
Cholinergic Modulation ◽  
Medial Nucleus ◽  
Trapezoid Body

The superior olivary complex (SOC) is a major computation center in the brainstem auditory system. Despite previous reports of high expression levels of cholinergic receptors in the SOC, few studies have addressed the functional role of acetylcholine in the region. The source of the cholinergic innervation is unknown for all but one of the nuclei of the SOC, limiting our understanding of cholinergic modulation. The medial nucleus of the trapezoid body, a key inhibitory link in monaural and binaural circuits, receives cholinergic input from other SOC nuclei and also from the pontomesencephalic tegmentum. Here, we investigate whether these same regions are sources of cholinergic input to other SOC nuclei. We also investigate whether individual cholinergic cells can send collateral projections bilaterally (i.e., into both SOCs), as has been shown at other levels of the subcortical auditory system. We injected retrograde tract tracers into the SOC in gerbils, then identified retrogradely-labeled cells that were also immunolabeled for choline acetyltransferase, a marker for cholinergic cells. We found that both the SOC and the pontomesencephalic tegmentum (PMT) send cholinergic projections into the SOC, and these projections appear to innervate all major SOC nuclei. We also observed a small cholinergic projection into the SOC from the lateral paragigantocellular nucleus of the reticular formation. These various sources likely serve different functions; e.g., the PMT has been associated with things such as arousal and sensory gating whereas the SOC may provide feedback more closely tuned to specific auditory stimuli. Further, individual cholinergic neurons in each of these regions can send branching projections into both SOCs. Such projections present an opportunity for cholinergic modulation to be coordinated across the auditory brainstem.

scholarly journals Frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Frédéric Doussau ◽  
Hartmut Schmidt ◽  
Kevin Dorgans ◽  
Antoine M Valera ◽  
Bernard Poulain ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Granule Cells ◽  
Low Frequency ◽  
Synaptic Activity ◽  
High Frequency Stimulation ◽  
Frequency Dependent ◽  
Short Term Plasticity ◽  
Readily Releasable Pool ◽  
Frequency Stimulation ◽  
Sensorimotor Information

The segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pools that are differentially poised for exocytosis shapes short-term plasticity. However, the frequency-dependent mobilization of these sub-pools is poorly understood. Using slice recordings and modeling of synaptic activity at cerebellar granule cell to Purkinje cell synapses of mice, we describe two sub-pools in the RRP that can be differentially recruited upon ultrafast changes in the stimulation frequency. We show that at low-frequency stimulations, a first sub-pool is gradually silenced, leading to full blockage of synaptic transmission. Conversely, a second pool of synaptic vesicles that cannot be released by a single stimulus is recruited within milliseconds by high-frequency stimulation and support an ultrafast recovery of neurotransmitter release after low-frequency depression. This frequency-dependent mobilization or silencing of sub-pools in the RRP in terminals of granule cells may play a role in the filtering of sensorimotor information in the cerebellum.

Changes in the Readily Releasable Pool of Transmitter and in Efficacy of Release Induced by High-Frequency Firing at Aplysia Sensorimotor Synapses in Culture

2004 ◽  
Vol 91 (4) ◽  
pp. 1500-1509 ◽  
Author(s):  
Yali Zhao ◽  
Marc Klein
Keyword(s):  
Motor Neuron ◽  
High Frequency ◽  
Transmitter Release ◽  
Action Potentials ◽  
High Frequency Stimulation ◽  
Hypertonic Solution ◽  
Posttetanic Potentiation ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Frequency Stimulation

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.

scholarly journals A frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity

2017 ◽  
Author(s):  
Frédéric Doussau ◽  
Hartmut Schmidt ◽  
Kevin Dorgans ◽  
Antoine M. Valera ◽  
Bernard Poulain ◽  
...  
Keyword(s):  
Granule Cell ◽  
Synaptic Vesicles ◽  
Low Frequency ◽  
Synaptic Activity ◽  
High Frequency Stimulation ◽  
Frequency Dependent ◽  
Readily Releasable Pool ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation

ABSTRACTThe segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pool which are differentially poised for exocytosis shapes short-term plasticity at depressing synapses. Here, we used in vitro recording and modeling of synaptic activity at the facilitating mice cerebellar granule cell to Purkinje cell synapse to demonstrate the existence of two sub-pools of vesicles in the RRP that can be differentially recruited upon fast changes in the stimulation frequency. We show that upon low-frequency stimulation, a population of fully-releasable vesicles is silenced, leading to full blockage of synaptic transmission. A second population of vesicles, reluctant to release by simple stimuli, is recruited in a millisecond time scale by high-frequency stimulation to support an ultrafast recovery of neurotransmitter release after low-frequency depression. The frequency-dependent mobilization or silencing of sub-pools of vesicles in granule cell terminals should play a major role in the filtering of sensorimotor information in the cerebellum.

The Superior Paraolivary Nucleus

2018 ◽  
pp. 394-420
Author(s):  
Anna K. Magnusson ◽  
Marcelo Gómez-Álvarez
Keyword(s):  
Auditory Brainstem ◽  
Superior Olivary Complex ◽  
High Survival ◽  
Complex Sounds ◽  
Robust Detection ◽  
Medial Nucleus ◽  
Superior Paraolivary Nucleus ◽  
The Brain ◽  
Trapezoid Body

This chapter summarizes the current concepts of the superior paraolivary nucleus (SPON)—a structure embedded in the superior olivary complex in the mammalian auditory brainstem. SPON is driven by input pathways from two of the most temporally secure neurons in the brain: the octopus cells in the cochlear nucleus and the neurons of the medial nucleus of the trapezoid body. These inputs activate spiking activity that marks the onset and offset of sound, the latter based on a rebound depolarization mechanism. This makes the SPON an excellent detector of transient sound energy. Robust detection of the coarse sound pattern over time further gives SPON the capacity to track the temporal envelope of complex sounds with supreme precision. Since the SPON circuitry is constant in mammals and resilient to sensory perturbation, it indicates its high survival value. A possible neuroevolutionary role of SPON in the processing of vocalizations is discussed.

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