The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning cognition. In present study, we used intracellular injections Lucifer yellow fixed tissue to analyse over 19 500 that were completely reconstructed three dimensions along length basal dendrites neurons parahippocampal cortex CA1 patients with Alzheimer's disease. Following injection, sections immunostained for anti-Lucifer...

Chandelier (or axo-axonic) cells are a distinct group of GABAergic interneurons that innervate the axon initial segments pyramidal and thus could have an important role controlling activity cortical circuits. To understand their connectivity, we labeled upper layers chandelier (ChCs) from mouse neocortex with genetic strategy studied how axons contact local populations neurons, using immunohistochemical detection segments. We ChCs located in border 1 2 primary somatosensory cortex found...

A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer's disease (AD). The beginning this has been associated with the very early, pathological accumulation tau and neuronal degeneration observed in entorhinal cortex (EC). Tau-related pathology thought to then spread progressively hippocampal formation other brain areas as progresses. major cortical afferent source hippocampus dentate gyrus EC through perforant pathway. At least two main circuits...

Although misfolded and aggregated α-synuclein (α-syn) is recognized in the disease progression of synucleinopathies, its role impairment cortical circuitries synaptic plasticity remains incompletely understood. We investigated how accumulation affects mouse somatosensory cortex using two distinct approaches. Long-term

Abstract Alzheimer’s disease is the most common form of dementia, characterized by a persistent and progressive impairment cognitive functions. typically associated with extracellular deposits amyloid-β peptide accumulation abnormally phosphorylated tau protein inside neurons (amyloid-β neurofibrillary pathologies). It has been proposed that these pathologies cause neuronal degeneration synaptic alterations, which are thought to constitute major neurobiological basis dysfunction in disease....

Synaptic dysfunction or loss in early stages of Alzheimer's disease (AD) is thought to be a major structural correlate cognitive dysfunction. Early episodic memory, which occurs at the stage AD, closely associated with progressive degeneration medial temporal lobe (MTL) structures transentorhinal cortex (TEC) first affected area. However, no ultrastructural studies have been performed this region human brain samples from AD patients. In present study, we detailed three-dimensional (3D)...

Abstract The transentorhinal cortex (TEC) is an obliquely oriented located in the medial temporal lobe and, together with entorhinal cortex, one of first affected areas Alzheimer’s disease (AD). One most widely accepted hypotheses that synaptopathy (synaptic alterations and loss) represents major structural correlate cognitive decline observed AD. However, very few electron microscope (EM) studies are available; common method to estimate synaptic density indirectly by counting, at light...

The quantification and measurement of synapses is a major goal in the study brain organization both health disease. Serial section electron microscopy (EM) ideal method since it permits direct crucial features such as number per unit volume or distribution size synapses. However, limitation that obtaining long series ultrathin sections extremely time-consuming difficult. Consequently, quantitative EM studies are scarce most common employed to estimate synaptic density human indirect, by...

Axonal dystrophies (AxDs) are swollen and tortuous neuronal processes that associated with extracellular depositions of amyloid β (Aβ) have been observed to contribute synaptic alterations occurring in Alzheimer's disease. Understanding the temporal course this axonal pathology is high relevance comprehend progression disease over time. We performed a long-term vivo study (up 210 days two-photon imaging) two transgenic mouse models (dE9xGFP-M APP-PS1xGFP-M). Interestingly, AxDs were formed...

Alzheimer’s disease (AD) is thought to be caused by accumulation of amyloid-β protein (Aβ), which a cleavage product amyloid precursor (APP). Transgenic mice overexpressing APP have been used recapitulate pathology. Among them, APP23 and APPswe/PS1deltaE9 (deltaE9) are extensively studied. express with Swedish mutation develop plaques late in their life, while cognitive deficits observed young age. In contrast, deltaE9 mutant presenilin-1 early but show typical old To unveil the reasons for...

The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying human brain via electron microscope techniques. However, we have shown that 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied study detail obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed...

Chandelier (or axo-axonic) cells are a distinct group of GABAergic interneurons that innervate the axon initial segments pyramidal and thus thought to have an important role in controlling activity cortical circuits. To examine circuit connectivity chandelier (ChCs), we made use genetic targeting strategy label neocortical ChCs upper layers juvenile mouse neocortex. We filled individual with biocytin living brain slices reconstructed their axonal arbors from serial semi-thin sections. also...

Summary Advances in the understanding of brain functions are closely linked to technical developments microscopy. In this study, we describe a correlative microscopy technique that offers possibility combining two‐photon vivo imaging with focus ion beam/scanning electron microscope (FIB/SEM) techniques. Long‐term allows visualization functional interactions within living organism over time, and therefore, is emerging as new tool for studying dynamics neurodegenerative diseases, such...

Abstract In recent years, numerous studies have shown that astrocytes play an important role in neuronal processing of information. One the most interesting findings is existence bidirectional interactions between neurons and at synapses, which has given rise to concept “tripartite synapses” from a functional point view. We used focused ion beam milling scanning electron microscopy (FIB/SEM) examine 3D relationship synapses with were previously labeled by intracellular injections rat...

The neurons in the cortical white matter (WM neurons) originate from first set of postmitotic that migrates ventricular zone. In particular, they arise subplate contains earliest cells generated telencephalon, prior to appearance gray layers. These WM are very numerous during development, when thought participate transient synaptic networks, although many these later die, and relatively few survive as adult. We used light electron microscopy analyze distribution density various areas adult...

A key symptom in the early stages of Alzheimer's disease (AD) is loss declarative memory. The anatomical substrate that supports this kind memory involves neural circuits medial temporal lobe, and particular, hippocampa

In Alzheimer's disease (AD), hallmark β-amyloid deposits are characterized by the presence of activated microglia around them. Despite an extensive characterization relation amyloid plaques with microglia, little is known about initiation this interaction. study, detailed investigation very small in brain slices AD transgenic mice line APP-PS1(dE9) revealed different levels recruitment. Analysing a diameter up to 10 μm we find that only half associated clear morphologically microglia....

Abstract 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 upper layers EC. present report, we examined Layers II and III from eight human brain autopsies (four subjects with no recorded neurologic four AD cases). We used stereological methods assess cortical atrophy EC possible changes volume occupied by different elements (neuronal glial cell bodies; blood vessels;...

Abstract The basic building block of the cerebral cortex, pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers, cortical areas, and species. Functionally, differences in their dendrites axons are critical determining how neurons integrate information. However, within human these have not quantified detail. In present work, we performed intracellular injections Lucifer Yellow 3D reconstructed over 200 neurons, including apical basal local...

Abstract The entorhinal cortex (EC) is a brain region that has been shown to be essential for memory functions and spatial navigation. However, detailed three-dimensional (3D) synaptic morphology analysis identification of postsynaptic targets at the ultrastructural level have not performed before in human EC. In present study, we used Focused Ion Beam/Scanning Electron Microscopy perform 3D synapses neuropil medial EC layers II III from autopsies. Specifically, studied structural parameters...

The main hallmarks of human hippocampal sclerosis are neuronal loss and gliosis; reductions in microvasculature labeling the cornu Ammonis 1 this condition have been detected using alkaline phosphatase histochemistry. To determine whether reduction inalkaline activity is coupled with a blood vessels,we examined volume fraction occupied by vessels toluidine blue-stained sections from 24 epilepsy patientresections (19 sclerosis, 5 without sclerosis) normal autopsy controls. Light electron...