scholarly journals Ultrastructural heterogeneity of human layer 4 excitatory synaptic boutons in the adult temporal lobe neocortex

2019 ◽  
Author(s):  
Rachida Yakoubi ◽  
Astrid Rollenhagen ◽  
Marec von Lehe ◽  
Dorothea Miller ◽  
Bernd Walkenfort ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Synaptic Vesicles ◽  
Building Blocks ◽  
Synaptic Activity ◽  
Quantitative Morphology ◽  
Layer 4 ◽  
Total Pool ◽  
Synaptic Boutons ◽  
Active Zones ◽  
Computational Properties

AbstractSynapses are fundamental building blocks that control and modulate the ‘behavior’ of brain networks. How their structural composition, most notably their quantitative morphology underlies their computational properties remains rather unclear, particularly in humans. Here, excitatory synaptic boutons (SBs) in layer 4 (L4) of the temporal lobe neocortex (TLN) were quantitatively investigated.Biopsies from epilepsy surgery were used for fine-scale and tomographic electron microscopy to generate 3D-reconstructions of SBs. Particularly, the size of active zones (AZs) and of the three functionally defined pools of synaptic vesicles (SVs) were quantified.SBs were comparably small (∼2.50 μm2), with a single AZ (∼0.13 µm2) and preferentially established on spines. SBs had a total pool of ∼1800SVs with strikingly large readily releasable (∼ 20), recycling (∼ 80) and resting pools (∼850).Thus, human L4 SBs may act as ‘amplifiers’ of signals from the sensory periphery and integrate, synchronize and modulate intra- and extra-cortical synaptic activity.

scholarly journals Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rachida Yakoubi ◽  
Astrid Rollenhagen ◽  
Marec von Lehe ◽  
Dorothea Miller ◽  
Bernd Walkenfort ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Synaptic Vesicles ◽  
Building Blocks ◽  
Synaptic Activity ◽  
Quantitative Morphology ◽  
Layer 4 ◽  
Total Pool ◽  
Synaptic Boutons ◽  
Computational Properties ◽  
Human Temporal Lobe

Synapses are fundamental building blocks controlling and modulating the ‘behavior’ of brain networks. How their structural composition, most notably their quantitative morphology underlie their computational properties remains rather unclear, particularly in humans. Here, excitatory synaptic boutons (SBs) in layer 4 (L4) of the temporal lobe neocortex (TLN) were quantitatively investigated. Biopsies from epilepsy surgery were used for fine-scale and tomographic electron microscopy (EM) to generate 3D-reconstructions of SBs. Particularly, the size of active zones (AZs) and that of the three functionally defined pools of synaptic vesicles (SVs) were quantified. SBs were comparatively small (~2.50 μm2), with a single AZ (~0.13 µm2); preferentially established on spines. SBs had a total pool of ~1800 SVs with strikingly large readily releasable (~20), recycling (~80) and resting pools (~850). Thus, human L4 SBs may act as ‘amplifiers’ of signals from the sensory periphery, integrate, synchronize and modulate intra- and extracortical synaptic activity.

scholarly journals Synaptic Organization of the Human Temporal Lobe Neocortex as Revealed by High-Resolution Transmission, Focused Ion Beam Scanning, and Electron Microscopic Tomography

2020 ◽  
Vol 21 (15) ◽  
pp. 5558
Author(s):  
Astrid Rollenhagen ◽  
Bernd Walkenfort ◽  
Rachida Yakoubi ◽  
Sarah A. Klauke ◽  
Sandra F. Schmuhl-Giesen ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Focused Ion Beam ◽  
Ion Beam ◽  
3D Models ◽  
Synaptic Organization ◽  
Experimental Animals ◽  
Synaptic Boutons ◽  
Active Zones ◽  
Em Tomography ◽  
Human Temporal Lobe

Modern electron microscopy (EM) such as fine-scale transmission EM, focused ion beam scanning EM, and EM tomography have enormously improved our knowledge about the synaptic organization of the normal, developmental, and pathologically altered brain. In contrast to various animal species, comparably little is known about these structures in the human brain. Non-epileptic neocortical access tissue from epilepsy surgery was used to generate quantitative 3D models of synapses. Beside the overall geometry, the number, size, and shape of active zones and of the three functionally defined pools of synaptic vesicles representing morphological correlates for synaptic transmission and plasticity were quantified. EM tomography further allowed new insights in the morphological organization and size of the functionally defined readily releasable pool. Beside similarities, human synaptic boutons, although comparably small (approximately 5 µm), differed substantially in several structural parameters, such as the shape and size of active zones, which were on average 2 to 3-fold larger than in experimental animals. The total pool of synaptic vesicles exceeded that in experimental animals by approximately 2 to 3-fold, in particular the readily releasable and recycling pool by approximately 2 to 5-fold, although these pools seemed to be layer-specifically organized. Taken together, synaptic boutons in the human temporal lobe neocortex represent unique entities perfectly adapted to the “job” they have to fulfill in the circuitry in which they are embedded. Furthermore, the quantitative 3D models of synaptic boutons are useful to explain and even predict the functional properties of synaptic connections in the human neocortex.

scholarly journals Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity

2019 ◽  
Vol 20 (11) ◽  
pp. 2692
Author(s):  
Jae Hoon Jung
Keyword(s):  
Synaptic Vesicles ◽  
Neuromuscular Junctions ◽  
Synaptic Activity ◽  
Membrane Thickness ◽  
Intermediate Step ◽  
Presynaptic Membrane ◽  
Vesicle Membrane ◽  
Contact Areas ◽  
Contact Sites ◽  
Active Zones

Synaptic vesicles dock on the presynaptic plasma membrane of axon terminals and become ready to fuse with the presynaptic membrane or primed. Fusion of the vesicle membrane and presynaptic membrane results in the formation of a pore between the membranes, through which the vesicle’s neurotransmitter is released into the synaptic cleft. A recent electron tomography study on frog neuromuscular junctions fixed at rest showed that there is no discernible gap between or merging of the membrane of docked synaptic vesicles with the presynaptic membrane, however, the extent of the contact area between the membrane of docked synaptic vesicles and the presynaptic membrane varies 10-fold with a normal distribution. The study also showed that when the neuromuscular junctions are fixed during repetitive electrical nerve stimulation, the portion of large contact areas in the distribution is reduced compared to the portion of small contact areas, suggesting that docked synaptic vesicles with the largest contact areas are greatly primed to fuse with the membrane. Furthermore, the finding of several hemifused synaptic vesicles among the docked vesicles was briefly reported. Here, the spatial relationship of 81 synaptic vesicles with the presynaptic membrane at active zones of the neuromuscular junctions fixed during stimulation is described in detail. For the most of the vesicles, the combined thickness of each of their contact sites was not different from the sum of the membrane thicknesses of the vesicle membrane and presynaptic membrane, similar to the docked vesicles at active zones of the resting neuromuscular junctions. However, the combined membrane thickness of a small portion of the vesicles was considerably less than the sum of the membrane thicknesses, indicating that the membranes at their contact sites were fixed in a state of hemifusion. Moreover, the hemifused vesicles were found to have large contact areas with the presynaptic membrane. These findings support the recently proposed hypothesis that, at frog neuromuscular junctions, docked synaptic vesicles with the largest contact areas are most primed for fusion with the presynaptic membrane, and that hemifusion is a fusion intermediate step of the vesicle membrane with the presynaptic membrane for synaptic transmission.

scholarly journals Author response: Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex

2019 ◽  
Author(s):  
Rachida Yakoubi ◽  
Astrid Rollenhagen ◽  
Marec von Lehe ◽  
Dorothea Miller ◽  
Bernd Walkenfort ◽  
...  
Keyword(s):  
Temporal Lobe ◽  
Author Response ◽  
Adult Human ◽  
Layer 4 ◽  
Synaptic Boutons ◽  
Human Temporal Lobe

A Simple Depletion Model of the Readily Releasable Pool of Synaptic Vesicles Cannot Account for Paired-Pulse Depression

2007 ◽  
Vol 97 (1) ◽  
pp. 948-950 ◽  
Author(s):  
Jane M. Sullivan
Keyword(s):  
Synaptic Vesicles ◽  
Hippocampal Neurons ◽  
Synaptic Activity ◽  
Excitatory Synapses ◽  
Short Term ◽  
Paired Pulse ◽  
Short Term Plasticity ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Paired Pulse Depression

Paired-pulse depression (PPD) is a form of short-term plasticity that plays a central role in processing of synaptic activity and is manifest as a decrease in the size of the response to the second of two closely timed stimuli. Despite mounting evidence to the contrary, PPD is still commonly thought to reflect depletion of the pool of synaptic vesicles available for release in response to the second stimulus. Here it is shown that PPD cannot be accounted for by depletion at excitatory synapses made by hippocampal neurons because PPD is unaffected by changes in the fraction of the readily releasable pool (RRP) released by the first of a pair of pulses.

scholarly journals Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites.

1978 ◽  
Vol 78 (1) ◽  
pp. 176-198 ◽  
Author(s):  
J R Sanes ◽  
L M Marshall ◽  
U J McMahan
Keyword(s):  
Skeletal Muscle ◽  
Basal Lamina ◽  
Muscle Fiber ◽  
Nerve Terminal ◽  
Synaptic Vesicles ◽  
Muscle Fibers ◽  
Nerve Terminals ◽  
Morphological Criteria ◽  
Histological Criteria ◽  
Active Zones

Axons regenerate to reinnervate denervated skeletal muscle fibers precisely at original synaptic sites, and they differentiate into nerve terminals where they contact muscle fibers. The aim of this study was to determine the location of factors that influence the growth and differentiation of the regenerating axons. We damaged and denervated frog muscles, causing myofibers and nerve terminals to degenerate, and then irradiated the animals to prevent regeneration of myofibers. The sheath of basal lamina (BL) that surrounds each myofiber survives these treatments, and original synaptic sites on BL can be recognized by several histological criteria after nerve terminals and muscle cells have been completely removed. Axons regenerate into the region of damage within 2 wk. They contact surviving BL almost exclusively at original synaptic sites; thus, factors that guide the axon's growth are present at synaptic sites and stably maintained outside of the myofiber. Portions of axons that contact the BL acquire active zones and accumulations of synaptic vesicles; thus by morphological criteria they differentiate into nerve terminals even though their postsynaptic targets, the myofibers, are absent. Within the terminals, the synaptic organelles line up opposite periodic specializations in the myofiber's BL, demonstrating that components associated with the BL play a role in organizing the differentiation of the nerve terminal.

scholarly journals Neocortical layer 4 in adult mouse differs in major cell types and circuit organization between primary sensory areas

2018 ◽  
Author(s):  
F. Scala ◽  
D. Kobak ◽  
S. Shan ◽  
Y. Bernaerts ◽  
S. Laturnus ◽  
...  
Keyword(s):  
Adult Mouse ◽  
Building Blocks ◽  
Cell Types ◽  
Excitatory Input ◽  
Excitatory Neurons ◽  
Layer 4 ◽  
Cell Type Specific ◽  
Fast Spiking ◽  
Mouse Visual Cortex ◽  
Whole Cell Recordings

AbstractLayer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM+) non-fast-spiking neurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM+ neurons were non-Martinotti. These morphologically distinct SOM+ interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell-type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are optionally used across the cortex as building blocks to assemble cortical circuits.

scholarly journals Vesicle capture by discrete self-assembled clusters of membrane-bound Munc13

2020 ◽  
Author(s):  
Feng Li ◽  
Venkat Kalyana Sundaram ◽  
Alberto T. Gatta ◽  
Jeff Coleman ◽  
Shyam S. Krishnakumar ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Self Assembly ◽  
Synaptic Vesicles ◽  
Supported Lipid Bilayers ◽  
Membrane Domains ◽  
Vesicle Docking ◽  
Multiple Copies ◽  
Membrane Bound ◽  
Small Unilamellar Vesicles ◽  
Active Zones

ABSTRACTMunc13 is a large banana-shaped soluble protein that is involved in the regulation of synaptic vesicle docking and fusion. Recent studies suggested that multiple copies of Munc13 form nanoassemblies in active zones of neurons. However, it is not known if such clustering is an inherent self-assembly property of Munc13 or whether Munc13 clusters indirectly by multivalent binding to synaptic vesicles or specific plasma membrane domains at docking sites in the active zone. The functional significance of putative Munc13 clustering is also unknown. Here we report that nano-clustering is an inherent property of Munc13, and is indeed required for vesicle binding to bilayers containing Munc13. Pure Munc13 reconstituted onto supported lipid bilayers assembled into clusters containing from 2 to ∼20 copies as revealed by a combination of quantitative TIRF microscopy and step-wise photobleaching. Surprisingly, only clusters a minimum of 6 copies of Munc13 were capable of efficiently capturing and retaining small unilamellar vesicles. The C-terminal C2C domain of Munc13 is not required for Munc13 clustering, but is required for efficient vesicle capture.

scholarly journals A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Yumei Wu ◽  
Eileen T O'Toole ◽  
Martine Girard ◽  
Brigitte Ritter ◽  
Mirko Messa ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Synaptic Vesicles ◽  
Synaptic Activity ◽  
Synaptic Vesicle Recycling ◽  
Knock Out ◽  
Knock Down ◽  
Vesicle Recycling ◽  
Subsequent Conversion ◽  
Insight Into

The exocytosis of synaptic vesicles (SVs) elicited by potent stimulation is rapidly compensated by bulk endocytosis of SV membranes leading to large endocytic vacuoles (‘bulk’ endosomes). Subsequently, these vacuoles disappear in parallel with the reappearance of new SVs. We have used synapses of dynamin 1 and 3 double knock-out neurons, where clathrin-mediated endocytosis (CME) is dramatically impaired, to gain insight into the poorly understood mechanisms underlying this process. Massive formation of bulk endosomes was not defective, but rather enhanced, in the absence of dynamin 1 and 3. The subsequent conversion of bulk endosomes into SVs was not accompanied by the accumulation of clathrin coated buds on their surface and this process proceeded even after further clathrin knock-down, suggesting its independence of clathrin. These findings support the existence of a pathway for SV reformation that bypasses the requirement for clathrin and dynamin 1/3 and that operates during intense synaptic activity.

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