scholarly journals Kinetic structure of recycling vesicle pool at the Calyx of Held synapse under in vivo-like activities

2021 ◽  
Author(s):  
Zili Liu ◽  
Ying Zhu ◽  
Yubing Hu ◽  
Jianyuan Sun
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Activity ◽  
Capacitance Measurement ◽  
Calyx Of Held ◽  
Physiological Temperature ◽  
Vesicle Recycling ◽  
Central Synapses ◽  
Vesicle Pool ◽  
The Impact

AbstractSynaptic transmission at mammalian central synapses has ongoing background activity at physiological temperature. The recycling vesicle pool, with proper kinetics, ensures sustained synaptic transmission. However, the kinetic structure of recycling vesicle pool has never been quantitatively analyzed before, and most studies were performed at room temperature and under resting conditions. With the combination of presynaptic capacitance measurement and postsynaptic EPSC recording on calyx of Held synapses at physiological temperature, we studied vesicle recycling under sustained presynaptic stimulation. The kinetics of vesicle reuse was revealed by impeding transmitter refilling with folimycin. We kinetically dissected the recycling vesicle pool as sequentially connected sub-pools and depicted the complete kinetic structure. The sizes and transition rates among these sub-pools were dynamically regulated by neuronal activity, in order to ensure efficient synaptic transmission. Our work highlights the impact of the vesicle recycling machinery on stable and reliable synaptic transmission under variable levels of neuronal activity.Impact statementThe recycling pool of vesicles are kinetically dissected as four populated pools ensuring stable and reliable synaptic transmission

scholarly journals Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus

2019 ◽  
Author(s):  
Felix C. Nebeling ◽  
Stefanie Poll ◽  
Lena C. Schmid ◽  
Manuel Mittag ◽  
Julia Steffen ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dendritic Spines ◽  
Synapse Formation ◽  
Brain Parenchyma ◽  
Two Photon ◽  
Contact Rates ◽  
Health And Disease ◽  
The Impact ◽  
The Brain

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.

scholarly journals Dual pools of actin at presynaptic terminals

2012 ◽  
Vol 107 (12) ◽  
pp. 3479-3492 ◽  
Author(s):  
Adam Bleckert ◽  
Huzefa Photowala ◽  
Simon Alford
Keyword(s):  
Synaptic Transmission ◽  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Repetitive Stimulation ◽  
Filamentous Actin ◽  
Cortical Actin ◽  
Vesicle Recycling ◽  
Latrunculin A ◽  
Kinetics Of

We investigated actin's function in vesicle recycling and exocytosis at lamprey synapses and show that FM1-43 puncta and phalloidin-labeled filamentous actin (F-actin) structures are colocalized, yet recycling vesicles are not contained within F-actin clusters. Additionally, phalloidin also labels a plasma membrane-associated cortical actin. Injection of fluorescent G-actin revealed activity-independent dynamic actin incorporation into presynaptic synaptic vesicle clusters but not into cortical actin. Latrunculin-A, which sequesters G-actin, dispersed vesicle-associated actin structures and prevented subsequent labeled G-actin and phalloidin accumulation at presynaptic puncta, yet cortical phalloidin labeling persisted. Dispersal of presynaptic F-actin structures by latrunculin-A did not disrupt vesicle clustering or recycling or alter the amplitude or kinetics of excitatory postsynaptic currents (EPSCs). However, it slightly enhanced release during repetitive stimulation. While dispersal of presynaptic actin puncta with latrunculin-A failed to disperse synaptic vesicles or inhibit synaptic transmission, presynaptic phalloidin injection blocked exocytosis and reduced endocytosis measured by action potential-evoked FM1-43 staining. Furthermore, phalloidin stabilization of only cortical actin following pretreatment with latrunculin-A was sufficient to inhibit synaptic transmission. Conversely, treatment of axons with jasplakinolide, which induces F-actin accumulation but disrupts F-actin structures in vivo, resulted in increased synaptic transmission accompanied by a loss of phalloidin labeling of cortical actin but no loss of actin labeling within vesicle clusters. Marked synaptic deficits seen with phalloidin stabilization of cortical F-actin, in contrast to the minimal effects of disruption of a synaptic vesicle-associated F-actin, led us to conclude that two structurally and functionally distinct pools of actin exist at presynaptic sites.

scholarly journals Quantitative analysis of vesicle recycling at the calyx of Held synapse

2015 ◽  
Vol 112 (15) ◽  
pp. 4779-4784 ◽  
Author(s):  
Xufeng Qiu ◽  
Qianwen Zhu ◽  
Jianyuan Sun
Keyword(s):  
Electron Microscopy ◽  
Quantitative Analysis ◽  
Kinetic Model ◽  
Temporal Resolution ◽  
Nerve Terminal ◽  
Calyx Of Held ◽  
Vesicle Recycling ◽  
Readily Releasable Pool ◽  
Vesicle Pool ◽  
Kinetics Of

Vesicle recycling is pivotal for maintaining reliable synaptic signaling, but its basic properties remain poorly understood. Here, we developed an approach to quantitatively analyze the kinetics of vesicle recycling with exquisite signal and temporal resolution at the calyx of Held synapse. The combination of this electrophysiological approach with electron microscopy revealed that ∼80% of vesicles (∼270,000 out of ∼330,000) in the nerve terminal are involved in recycling. Under sustained stimulation, recycled vesicles start to be reused in tens of seconds when ∼47% of the preserved vesicles in the recycling pool (RP) are depleted. The heterogeneity of vesicle recycling as well as two kinetic components of RP depletion revealed the existence of a replenishable pool of vesicles before the priming stage and led to a realistic kinetic model that assesses the size of the subpools of the RP. Thus, our study quantified the kinetics of vesicle recycling and kinetically dissected the whole vesicle pool in the calyceal terminal into the readily releasable pool (∼0.6%), the readily priming pool (∼46%), the premature pool (∼33%), and the resting pool (∼20%).

Physical exercise decreases neuronal activity in the posterior hypothalamic area of spontaneously hypertensive rats

2005 ◽  
Vol 98 (2) ◽  
pp. 572-578 ◽  
Author(s):  
Joseph A. Beatty ◽  
Jeffery M. Kramer ◽  
Edward D. Plowey ◽  
Tony G. Waldrop
Keyword(s):  
Physical Exercise ◽  
Neuronal Activity ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Hypothalamic Area ◽  
Spontaneously Hypertensive ◽  
Firing Rates ◽  
The Impact

Recently, physical exercise has been shown to significantly alter neurochemistry and neuronal function and to increase neurogenesis in discrete brain regions. Although we have documented that physical exercise leads to molecular changes in the posterior hypothalamic area (PHA), the impact on neuronal activity is unknown. The purpose of the present study was to determine whether neuronal activity in the PHA is altered by physical exercise. Spontaneously hypertensive rats (SHR) were allowed free access to running wheels for a period of 10 wk (exercised group) or no wheel access at all (nonexercised group). Single-unit extracellular recordings were made in anesthetized in vivo whole animal preparations or in vitro brain slice preparations. The spontaneous firing rates of PHA neurons in exercised SHR in vivo were significantly lower (8.5 ± 1.6 Hz, n = 31 neurons) compared with that of nonexercised SHR in vivo (13.7 ± 1.8 Hz, n = 38 neurons; P < 0.05). In addition, PHA neurons that possessed a cardiac-related rhythm in exercised SHR fired significantly lower (6.0 ± 1.8 Hz, n = 11 neurons) compared with nonexercised SHR (12.1 ± 2.4 Hz, n = 18 neurons; P < 0.05). Similarly, the spontaneous in vitro firing rates of PHA neurons from exercised SHR were significantly lower (3.5 ± 0.3 Hz, n = 67 neurons) compared with those of nonexercised SHR (5.6 ± 0.5 Hz, n = 58 neurons; P < 0.001). Both the in vivo and in vitro findings support the hypothesis that physical exercise can lower spontaneous activity of neurons in a cardiovascular regulatory region of the brain. Thus physical exercise may alter central neural control of cardiovascular function by inducing lasting changes in neuronal activity.

scholarly journals Synaptic Transmission at the Calyx of Held Under In Vivo–Like Activity Levels

2007 ◽  
Vol 98 (2) ◽  
pp. 807-820 ◽  
Author(s):  
Joachim Hermann ◽  
Michael Pecka ◽  
Henrique von Gersdorff ◽  
Benedikt Grothe ◽  
Achim Klug
Keyword(s):  
Synaptic Transmission ◽  
Brain Stem ◽  
Spontaneous Activity ◽  
Afferent Fiber ◽  
High Frequency Stimulation ◽  
Mongolian Gerbils ◽  
Calyx Of Held ◽  
Sensory Stimuli

One of the hallmarks of auditory neurons in vivo is spontaneous activity that occurs even in the absence of any sensory stimuli. Sound-evoked bursts of discharges are thus embedded within this background of random firing. The calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB) has been characterized in vitro as a fast relay that reliably fires at high stimulus frequencies (≤800 Hz). However, inherently due to the preparation method, spontaneous activity is absent in studies using brain stem slices. Here we first determine in vivo spontaneous firing rates of MNTB principal cells from Mongolian gerbils and then reintroduce this random firing to in vitro gerbil brain stem synapses at near-physiological temperature. After conditioning synapses with afferent fiber stimulation for 2 min at Poisson averaged rates of 20, 40, and 60 Hz, we observed a number of differences in the properties of synaptic transmission between conditioned and unconditioned synapses. Foremost, we observed reduced steady-state EPSC amplitudes that depressed even further during an embedded short-stimulation train of 100, 300, or 600 Hz (a protocol that thus simulates in vitro what probably occurs at the in vivo MNTB after a short sound stimulus in a silent background). Accordingly, current-clamp, dynamic-clamp, and loose-patch recordings revealed a number of action potential failures at the postsynaptic cell during high-frequency–stimulation trains, although the initial onset of evoked activity was still transmitted with higher fidelity. We thus propose that some in vivo auditory synapses are in a tonic state of reduced EPSC amplitudes as a consequence of high spontaneous spiking and this in vivo–like conditioning has important consequences for the encoding of signals throughout the auditory pathway.

Spike Transmission Delay at the Calyx of Held In Vivo: Rate Dependence, Phenomenological Modeling, and Relevance for Sound Localization

2009 ◽  
Vol 102 (2) ◽  
pp. 1206-1217 ◽  
Author(s):  
Sandra Tolnai ◽  
Bernhard Englitz ◽  
Jonathan Scholbach ◽  
Jürgen Jost ◽  
Rudolf Rübsamen
Keyword(s):  
Action Potential ◽  
Sound Localization ◽  
Temporal Dynamics ◽  
Transmission Delay ◽  
Mongolian Gerbils ◽  
Calyx Of Held ◽  
Time Constants ◽  
Medial Nucleus ◽  
Central Synapses

Transmission at central synapses exhibits rapid changes in response amplitude under different patterns of stimulation. Whether the delay associated with the transmission of action potentials is similarly modifiable is important for temporally precise computations. We address this question at the calyx of Held of the medial nucleus of the trapezoid body (MNTB) in Mongolian gerbils in vivo using extracellular recordings. Here the pre- and postsynaptic activity can be observed simultaneously, allowing the definition of an action potential transmission delay (ATD) from the pre- to the postsynaptic side. We find the ATD to increase as a function of spike rate (10–40%). The temporal dynamics of the ATD increase exhibit an exponential shape with activity-dependent time constants (∼15–25 ms). Recovery dynamics of ATD were mono- (20–70 ms) or biexponential with fast (3–20 ms) and slow time constants (50–500 ms). Using a phenomenological model to capture ATD dynamics, we estimated ΔATD = 5–30 μs per transmitted action potential. Using vocalizations and cage noise stimuli, we confirm that substantial changes in ATD occur in natural situations. Because the ATD changes cover the behaviorally relevant range of interaural time differences in gerbils, these results could provide constraints for models of sound localization.

scholarly journals Activity-dependent regulation of mitochondrial motility in developing cortical dendrites

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Catia AP Silva ◽  
Annik Yalnizyan-Carson ◽  
M Victoria Fernández Busch ◽  
Mike van Zwieten ◽  
Matthijs Verhage ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Neuronal Activity ◽  
High Rate ◽  
Atp Production ◽  
Mitochondrial Motility ◽  
Regulation Mechanisms ◽  
Developing Neurons ◽  
Synaptic Vesicle Release ◽  
Activity Dependent

Developing neurons form synapses at a high rate. Synaptic transmission is very energy-demanding and likely requires ATP production by mitochondria nearby. Mitochondria might be targeted to active synapses in young dendrites, but whether such motility regulation mechanisms exist is unclear. We investigated the relationship between mitochondrial motility and neuronal activity in the primary visual cortex of young mice in vivo and in slice cultures. During the first 2 postnatal weeks, mitochondrial motility decreases while the frequency of neuronal activity increases. Global calcium transients do not affect mitochondrial motility. However, individual synaptic transmission events precede local mitochondrial arrest. Pharmacological stimulation of synaptic vesicle release, but not focal glutamate application alone, stops mitochondria, suggesting that an unidentified factor co-released with glutamate is required for mitochondrial arrest. A computational model of synaptic transmission-mediated mitochondrial arrest shows that the developmental increase in synapse number and transmission frequency can contribute substantially to the age-dependent decrease of mitochondrial motility.

scholarly journals Wide-Band Information Transmission at the Calyx of Held

2009 ◽  
Vol 21 (4) ◽  
pp. 991-1017 ◽  
Author(s):  
Zhijun Yang ◽  
Matthias H. Hennig ◽  
Michael Postlethwaite ◽  
Ian D. Forsythe ◽  
Bruce P. Graham
Keyword(s):  
Information Transmission ◽  
Wide Band ◽  
Interspike Intervals ◽  
Calyx Of Held ◽  
Low Frequencies ◽  
Postsynaptic Response ◽  
Vesicle Recycling ◽  
Significant Depression ◽  
The Impact

We use a mathematical model of the calyx of Held to explore information transmission at this giant glutamatergic synapse. The significant depression of the postsynaptic response to repeated stimulation in vitro is a result of various activity-dependent processes in multiple timescales, which can be reproduced by multiexponential functions in this model. When the postsynaptic current is stimulated by Poisson-distributed spike trains, its amplitude varies considerably with the preceding interspike intervals. Here we quantify the information contained in the postsynaptic current amplitude about preceding interspike intervals and determine the impact of different pre- and postsynaptic factors on information transmission. The mutual information between presynaptic spike times and the amplitude of the postsynaptic response in general decreases as the mean stimulation rate increases, but remains high even at frequencies greater than 100 Hz, unlike at many neocortical synapses. The maintenance of information transmission is attributable largely to vesicle recycling rates at low frequencies of stimulation, shifting to vesicle release probability at high frequencies. Also, at higher frequencies, the synapse operates largely in a release-ready mode in which most release sites contain a release-ready vesicle and release probabilities are low.

scholarly journals How Secure Is In Vivo Synaptic Transmission at the Calyx of Held?

2008 ◽  
Vol 28 (41) ◽  
pp. 10206-10219 ◽  
Author(s):  
M. Mc Laughlin ◽  
M. van der Heijden ◽  
P. X. Joris
Keyword(s):  
Synaptic Transmission ◽  
Calyx Of Held
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