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

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.

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

10.1101/643924 ◽

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.

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Decision letter: Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex

10.7554/elife.48373.sa1 ◽

2019 ◽

Author(s):

Kathleen Rockland

Keyword(s):

Temporal Lobe ◽

Adult Human ◽

Layer 4 ◽

Synaptic Boutons ◽

Human Temporal Lobe

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

10.7554/elife.48373.sa2 ◽

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

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

International Journal of Molecular Sciences ◽

10.3390/ijms21155558 ◽

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.

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Quantitative Three-Dimensional Reconstructions of Excitatory Synaptic Boutons in Layer 5 of the Adult Human Temporal Lobe Neocortex: A Fine-Scale Electron Microscopic Analysis

Cerebral Cortex ◽

10.1093/cercor/bhy146 ◽

2018 ◽

Vol 29 (7) ◽

pp. 2797-2814 ◽

Cited By ~ 15

Author(s):

Rachida Yakoubi ◽

Astrid Rollenhagen ◽

Marec von Lehe ◽

Yachao Shao ◽

Kurt Sätzler ◽

...

Keyword(s):

Temporal Lobe ◽

Three Dimensional ◽

Microscopic Analysis ◽

Synaptic Cleft ◽

Brain Regions ◽

Fine Scale ◽

Electron Microscopic ◽

Readily Releasable Pool ◽

Synaptic Boutons ◽

Human Temporal Lobe

Abstract Studies of synapses are available for different brain regions of several animal species including non-human primates, but comparatively little is known about their quantitative morphology in humans. Here, synaptic boutons in Layer 5 (L5) of the human temporal lobe (TL) neocortex were investigated in biopsy tissue, using fine-scale electron microscopy, and quantitative three-dimensional reconstructions. The size and organization of the presynaptic active zones (PreAZs), postsynaptic densities (PSDs), and that of the 3 distinct pools of synaptic vesicles (SVs) were particularly analyzed. L5 synaptic boutons were medium-sized (~6 μm2) with a single but relatively large PreAZ (~0.3 μm2). They contained a total of ~1500 SVs/bouton, ~20 constituting the putative readily releasable pool (RRP), ~180 the recycling pool (RP), and the remainder, the resting pool. The PreAZs, PSDs, and vesicle pools are ~3-fold larger than those of CNS synapses in other species. Astrocytic processes reached the synaptic cleft and may regulate the glutamate concentration. Profound differences exist between synapses in human TL neocortex and those described in various species, particularly in the size and geometry of PreAZs and PSDs, the large RRP/RP, and the astrocytic ensheathment suggesting high synaptic efficacy, strength, and modulation of synaptic transmission at human synapses.

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