Three-dimensional synaptic organization of layer III of the human temporal neocortex

Cano‐Astorga, Nicolás; DeFelipe, Javier; Alonso‐Nanclares, Lidia

doi:10.1101/2021.01.18.427131

Cited by 9 publications

(35 citation statements)

References 102 publications

(230 reference statements)

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“…In addition, the majority of the synapses that a pyramidal cell receives are on spines and they represent the vast majority of AS synapses (DeFelipe and Fariñas, 1992). In the human transentorhinal cortex, 75% of the synapses were AS on spines, which is similar to the case of the AS found in the layer III of the temporal cortex (75%) using the same analysis method (Cano-Astorga et al, 2021). This percentage was much higher in the CA1 hippocampal field, as high as 94% in the superficial part of the CA1 stratum pyramidale (Montero-Crespo et al, 2020).…”

Section: Postsynaptic Targetssupporting

confidence: 56%

“…Finally, the present results indicate that the distribution of synapses in the neuropil of both control and AD samples is nearly random, only constrained by the fact that synapses cannot physically overlap in space and so their geometric centers or centroids cannot be too close to their neighbors. As we have previously shown in human brain samples from hippocampal CA1, entorhinal cortex, transentorhinal cortex and temporal cortex, there seems to be no limitation to the position of any synapse except the space already occupied by other synapses (Montero-Crespo et al, 2020;Domínguez-Álvaro et al, 2018Domínguez-Álvaro et al, , 2021Cano-Astorga et al, 2021). Previous studies in the plaque-free neuropil of AD cases also showed a random distribution pattern of the synapses in other brain regions (Blazquez-Llorca et al, 2013, Domínguez-Álvaro et al, 2018Montero-Crespo et al, 2021).…”

Section: Synaptic Density Proportions and Spatial Distributionmentioning

confidence: 63%

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3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer’s disease

Domínguez-Álvaro

Montero-Crespo²,

Blázquez-Llorca³

et al. 2020

Preprint

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The entorhinal cortex (EC) is especially vulnerable in the early stages of Alzheimer's disease (AD). In particular, cognitive deficits have been linked to alterations in the upper layers of EC. In the present report, we performed light microscopy analysis and 3D ultrastructural analyses of synapses in the EC using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to examine possible alterations related to AD. We analyzed 5000 synaptic junctions that were 3D reconstructed, representing the largest 3D ultrastructural study of synapses in the EC of the human brain from cases with AD performed to date. Structural differences were found in the AD tissue at the light microscope level and at the ultrastructural level. These differences may play a role in the anatomical basis for the impairment of cognitive functions in AD.

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Section: Postsynaptic Targetssupporting

confidence: 56%

Section: Synaptic Density Proportions and Spatial Distributionmentioning

confidence: 63%

3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer’s disease

Domínguez-Álvaro

Montero-Crespo²,

Blázquez-Llorca³

et al. 2020

Preprint

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“…In order to compare their selection of output synapse locations to the distribution of potential GABAergic synaptic target sites in the neuropil, we have studied the distribution of GABAergic synapses on dendritic spines and shafts in layer III. Using post-embedding immunogold reactions with antibodies to GABA in electron-microscopic sections (Somogyi & Soltész, 1986) and a stereological method based on 3D tracing of synapses and their targets in a defined volume through serial sections (West, 1999; Cano-Astorga et al, 2021) we determined the numerical density and the proportion of GABAergic synapses and their neuropil targets in samples from temporal and frontal cortices.…”

Section: Resultsmentioning

confidence: 99%

Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex

Lukacs

Francavilla

Field

et al. 2022

Preprint

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Diverse neocortical GABAergic neurons specialise in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in two distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBC) had columnar “horsetail” axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and non-pyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%) and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline), but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialised, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.

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“…Likewise, the reduction in spinous synapse areas in CA1 and dlPFC of monkeys exposed to neonatal anesthesia implies an enduring loss of excitatory synapse coverage with specific long-term consequences for the makeup of excitatory receptors, and by extension excitatory neurotransmission, in both regions. Almost all (91-99%) spinous synapses in the CA1 and cortex of rodents and primates are excitatory, as demonstrated by their asymmetry (Blazquez-Llorca et al, 2021; Cano-Astorga et al, 2021; Domínguez-Álvaro et al, 2019; Hsu et al, 2017; Montero-Crespo et al, 2020; Santuy et al, 2018; Tao et al, 2018). Thus, the reductions in spinous synapse areas by early-life anesthesia in the present cohort of monkeys are likely highly specific to excitatory synapses.…”

Section: Discussionmentioning

confidence: 99%

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

Fehr

Janssen

Park

et al. 2022

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Early-life exposure to anesthesia in infant humans and monkeys increases the risk for cognitive and socioemotional impairments. However, the long-term effects of neonatal anesthesia on synaptic ultrastructure have not been thoroughly investigated in primates. We used electron microscopy with unbiased stereological sampling to assess synaptic ultrastructure in the CA1 of the hippocampus and the dorsolateral prefrontal cortex (dlPFC) of female and male rhesus macaques four years after three 4-hour exposures to sevoflurane during the first five postnatal weeks. We counted synapses and measured synapse areas for all synapses and those classified as perforated or nonperforated with spine or dendritic shaft targets. We measured numbers and shapes of mitochondria within presynaptic boutons and calculated vesicle docking rates. In monkeys exposed to anesthesia as infants, synapse areas were reduced in the largest 20% of synapses in CA1 and the largest 5% of synapses in dlPFC, with differential sex effects for the largest 10% of synapses in CA1. Synapse areas were reduced by 7.6% for perforated spinous synapses in CA1, and by 10.4% for nonperforated spinous synapses in dlPFC. Perforated and nonperforated dendritic synapse numbers in CA1 increased by 180% and 63% respectively. Curved mitochondria decreased 25% in CA1 after anesthesia exposure, and dlPFC boutons with 0 mitochondria showed an interaction of anesthesia and sex. These results demonstrate that exposure to anesthesia in infancy can cause long-term structural deficits in primates. These structural changes may be substrates for long-term alterations in the strength and efficiency of synaptic transmission in hippocampus and prefrontal cortex.Key pointsExposure to anesthesia in early life causes lasting cognitive and socioemotional impairments in human and nonhuman primates, but the extent to which early-life exposure to anesthesia alters synaptic ultrastructure in later life has not been known.Four years after rhesus monkeys were given multiple exposures to anesthesia in infancy, the area of spinous synapses was reduced in CA1 and dlPFC, dendritic synapse numbers were elevated in CA1, there were fewer curved presynaptic mitochondria in CA1, and numbers of presynaptic boutons without mitochondria were altered in dlPFC.The long-term ultrastructural changes to synapses and presynaptic mitochondria of rhesus monkeys that were exposed to anesthesia as infants could help explain their behavioral deficits later in life.

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Three-dimensional synaptic organization of layer III of the human temporal neocortex

Cited by 9 publications

References 102 publications

3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer’s disease

3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer’s disease

Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex

Neonatal exposures to sevoflurane in rhesus monkeys alter synaptic ultrastructure in later life

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