3D Ultrastructure of Synaptic Inputs to Distinct GABAergic Neurons in the Mouse Primary Visual Cortex.

Synapses are the fundamental elements of the brain's complicated neural networks. Although the ultrastructure of synapses has been extensively studied, the difference in how synaptic inputs are organized onto distinct neuronal types is not yet fully understood. Here, we examined the cell-type-specific ultrastructure of proximal processes from the soma of parvalbumin-positive (PV+) and somatostatin-positive (SST+) GABAergic neurons in comparison with a pyramidal neuron in the mouse primary visual cortex (V1), using serial block-face scanning electron microscopy. Interestingly, each type of neuron organizes excitatory and inhibitory synapses in a unique way. First, we found that a subset of SST+ neurons are spiny, having spines on both soma and dendrites. Each of those spines has a highly complicated structure that has up to eight synaptic inputs. Next, the PV+ and SST+ neurons receive more robust excitatory inputs to their perisoma than does the pyramidal neuron. Notably, excitatory synapses on GABAergic neurons were often multiple-synapse boutons, making another synapse on distal dendrites. On the other hand, inhibitory synapses near the soma were often single-targeting multiple boutons. Collectively, our data demonstrate that synaptic inputs near the soma are differentially organized across cell types and form a network that balances inhibition and excitation in the V1.

A sexually dimorphic hepatic cycle of periportal VLDL generation and subsequent pericentral VLDLR-mediated re-uptake.

Recent single-cell transcriptomes revealed spatiotemporal programmes of liver function on the sublobular scale. However, how sexual dimorphism affected this space-time logic remained poorly understood. We addressed this by performing scRNA-seq in the mouse liver, which revealed that sex, space and time together markedly influence xenobiotic detoxification and lipoprotein metabolism. The very low density lipoprotein receptor (VLDLR) exhibits a pericentral expression pattern, with significantly higher mRNA and protein levels in female mice. Conversely, VLDL assembly is periportally biased, suggesting a sexually dimorphic hepatic cycle of periportal formation and pericentral uptake of VLDL. In humans, VLDLR expression is also pericentral, with higher mRNA and protein levels in premenopausal women compared to similarly aged men. Individuals with low hepatic VLDLR expression show a high prevalence of atherosis in the coronary artery already at an early age and an increased incidence of heart attack.

A subpopulation of cortical VIP-expressing interneurons with highly dynamic spines.

Structural synaptic plasticity may underlie experience and learning-dependent changes in cortical circuits. In contrast to excitatory pyramidal neurons, insight into the structural plasticity of inhibitory neurons remains limited. Interneurons are divided into various subclasses, each with specialized functions in cortical circuits. Further knowledge of subclass-specific structural plasticity of interneurons is crucial to gaining a complete mechanistic understanding of their contribution to cortical plasticity overall. Here, we describe a subpopulation of superficial cortical multipolar interneurons expressing vasoactive intestinal peptide (VIP) with high spine densities on their dendrites located in layer (L) 1, and with the electrophysiological characteristics of bursting cells. Using longitudinal imaging in vivo, we found that the majority of the spines are highly dynamic, displaying lifetimes considerably shorter than that of spines on pyramidal neurons. Using correlative light and electron microscopy, we confirmed that these VIP spines are sites of excitatory synaptic contacts, and are morphologically distinct from other spines in L1.

The Dark Purple Side of Ceftriaxone: A Case Report on Leucocytoclastic Vasculitis.

We present a case of an 85-year-old woman diagnosed with uncomplicated pyelonephritis, who was treated with intravenous ceftriaxone. Her chronic medications were phenprocoumon, diltiazem and bisoprolol. During the infectious phase, the patient presented tachycardia - despite high-dose beta-blocker treatment - and developed left acute heart failure, with acute renal failure (pre-renal origin). After introduction of furosemide diuretic therapy, clinical conditions improved and better control of the volemic status and heart rate was achieved. Several days after ceftriaxone and digoxin therapy initiation, worsening multiple non-blanching palpable purpuric lesions with bullae and papules, limited to the lower extremities, were noted. Skin biopsy was performed and a diagnosis of leucocytoclastic vasculitis, with associated panniculitis, was made. Ceftriaxone was discontinued and systemic corticosteroids were introduced, with a clear improvement in the cutaneous condition. LEARNING POINTS: Leucocytoclastic vasculitis is a rare but significant side effect related to the administration of ceftriaxone.The importance of skin biopsy in the differential diagnosis of skin eruptions.

Ultrastructural comparison of dendritic spine morphology preserved with cryo and chemical fixation.

Previously, we showed that cryo fixation of adult mouse brain tissue gave a truer representation of brain ultrastructure in comparison with a standard chemical fixation method (Korogod et al., 2015). Extracellular space matched physiological measurements, there were larger numbers of docked vesicles and less glial coverage of synapses and blood capillaries. Here, using the same preservation approaches, we compared the morphology of dendritic spines. We show that the length of the spine and the volume of its head is unchanged; however, the spine neck width is thinner by more than 30% after cryo fixation. In addition, the weak correlation between spine neck width and head volume seen after chemical fixation was not present in cryo-fixed spines. Our data suggest that spine neck geometry is independent of the spine head volume, with cryo fixation showing enhanced spine head compartmentalization and a higher predicted electrical resistance between spine head and parent dendrite.

Pancreatic Pseudocysts in the Mediastinal Space: An Urban Legend?

Pancreatic pseudocysts are a frequent complication of chronic pancreatitis. Nonetheless, they seldom extend beyond the peripancreatic region. However, migration towards the mediastinum may cause heterogeneous and non-specific symptoms, such as dysphagia, chest pain and dyspnoea, which depend on the localization and extension of the cysts. We present the case of a patient with chronic pancreatitis who was admitted to our ward for low-grade fever and mild dyspnoea and who rapidly developed bilateral laterocervical swelling associated with acute dyspnoea and trismus. A total body CT scan showed multiple abdominal pancreatic pseudocysts, one of which had migrated to the mediastinum and towards the retropharyngeal space. Clinicians should always consider the possibility of extra-pancreatic pseudocysts in patients with known pancreatitis so that uncommon clinical presentations with a potentially fatal outcome will be recognized. LEARNING POINTS: Mediastinal pancreatic pseudocysts are a rare manifestation of acute and chronic pancreatitis.The clinical presentation of mediastinal pancreatic pseudocysts is variable, and they may rarely have a fatal outcome.

NeuroMorph: A Software Toolset for 3D Analysis of Neurite Morphology and Connectivity.

The geometries of axons, dendrites and their synaptic connections provide important information about their functional properties. These can be collected directly from measurements made on serial electron microscopy images. However, manual and automated segmentation methods can also yield large and accurate models of neuronal architecture from which morphometric data can be gathered in 3D space. This technical paper presents a series of software tools, operating in the Blender open source software, for the quantitative analysis of axons and their synaptic connections. These allow the user to annotate serial EM images to generate models of different cellular structures, or to make measurements of models generated in other software. The paper explains how the tools can measure the cross-sectional surface area at regular intervals along the length of an axon, and the amount of contact with other cellular elements in the surrounding neuropil, as well as the density of organelles, such as vesicles and mitochondria, that it contains. Nearest distance measurements, in 3D space, can also be made between any features. This provides many capabilities such as the detection of boutons and the evaluation of different vesicle pool sizes, allowing users to comprehensively describe many aspects of axonal morphology and connectivity.