Pharmacokinetics of 1,25-dihydroxyvitamin D3 glycosides from Solanum glaucophyllum extract given in a rumen bolus on blood mineral profiles in dry pregnant dairy cows.

Providing tablets of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the biologically active metabolite of vitamin D3, in a rumen bolus may be used as prevention for periparturient hypocalcemia in dairy cows. This study investigated the pharmacokinetics of 1,25(OH)2D3 glycosides extracted from Solanum glaucophyllum (SGE) on blood serum 1,25(OH)2D3, Ca, P and Mg response in dry pregnant dairy cows. Boluses contained tablets of SGE which differed in their release properties (rapid release, slow release and combination) and galenics (200 μg uncoated, 300 μg and 500 μg uncoated or coated, 2 × 500 μg uncoated). Nineteen blood samples were collected from 29 cows between 96 h before and 336 h after bolus administration. Blood serum 1,25(OH)2D3, Ca and P increased between 12 h and 120 h, 12 h and 264 h and 24 h and 264 h, respectively. Highest values were reached at 30 h, 72 h and 120 h for 1,25(OH)2D3, Ca and P, respectively. Baseline values were then reached at 216 h for 1,25(OH)2D3 and 336 h for Ca and P. Concentration of Mg decreased between 24 h and 216 h, before reaching values comparable to baseline at 264 h. Highest Ca values were obtained with the combined rapid and slow release properties (500 μg) and there was no effect from coating on pharmacokinetics. In conclusion, the antepartum oral SGE bolus administration may be suitable for the prevention of periparturient hypocalcemia

Potential of a rumen bolus containing 1,25-dihydroxyvitamin D3 glycosides for the prevention of hypocalcaemia in primiparous and multiparous dairy cows

Periparturient hypocalcaemia is a widespread metabolic disorder in dairy cows. Clinical and subclinical cases occur primarily in multiparous (Multi) cows, but subclinical cases have also been reported in primiparous (Primi) cows. A preventive strategy was investigated by administering the physiologically active vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol, 1,25(OH)2D3) as a rumen bolus. The bolus contained tablets of 1,25(OH)2D3 glycoside extract from Solanum glaucophyllum (SGE), releasing SGE over several days. The aim was to study the effect of a bolus containing 0 (C) or 500 µg (SGE) of 1,25(OH)2D3 on 1,25(OH)2D3 and mineral status in periparturient cows up to three weeks into lactation and on colostrum, milk and calves' blood mineral contents. The bolus was administered three to four days prior to expected calving to Primi and Multi cows fed a herbage-based diet (dietary cation-anion difference of +522 mEq/kg DM). One C or SGE bolus was applied to 12 Primi and 12 Multi cows. Blood was regularly sampled (and selected a posteriori for antepartum samples) in regard to the actual calving day (d0), immediately prior to bolus application and at day -2, 0.5, 1, 1.5, 2, 4, 8, 11, 15, 18 and 22. Additional samples included urine (at bolus application, d0.5 and d2), colostrum, milk samples (weekly) and calves' blood (d2). Blood serum 1,25(OH)2D3 increased between d0.5 and d2 in Primi-SGE, but remained unchanged in Primi-C, as did parathyroid hormone (PTH) and Ca in all Primi. Urinary Ca of Primi-SGE was increased on d2, indicating regulation of Ca excess. Three Multi-C cows with confirmed clinical hypocalcaemia needed treatment and thus were excluded from the dataset and replaced. Blood serum 1,25(OH)2D3 and PTH increased while Ca dropped by 40% between d0.5 and d2 in Multi-C, whereas 1,25(OH)2D3, Ca and PTH remained unchanged in Multi-SGE. Blood serum carboxyterminal telopeptide of type I collagen was higher in Primi than in Multi and increased with time, except in Primi-C. Mineral contents in colostrum, milk and blood serum of calves were not influenced to a relevant degree. In conclusion, Primi-C did not, in contrast to Multi-C, develop subclinical hypocalcaemia (<2.0 mmol Ca/l). Prevention of hypocalcaemia with one SGE bolus applied three to four days prior to expected calving was successful in maintaining blood Ca within normal range in Multi over the critical first two days and up to the first three weeks of lactation, without any observed detrimental effects on cows or calves

Cell Type–Specific Thalamic Innervation in a Column of Rat Vibrissal Cortex

This is the concluding article in a series of 3 studies that investigate the anatomical determinants of thalamocortical (TC) input to excitatory neurons in a cortical column of rat primary somatosensory cortex (S1). We used viral synaptophysin-enhanced green fluorescent protein expression in thalamic neurons and reconstructions of biocytin-labeled cortical neurons in TC slices to quantify the number and distribution of boutons from the ventral posterior medial (VPM) and posteromedial (POm) nuclei potentially innervating dendritic arbors of excitatory neurons located in layers (L)2–6 of a cortical column in rat somatosensory cortex. We found that 1) all types of excitatory neurons potentially receive substantial TC input (90–580 boutons per neuron); 2) pyramidal neurons in L3–L6 receive dual TC input from both VPM and POm that is potentially of equal magnitude for thick-tufted L5 pyramidal neurons (ca. 300 boutons each from VPM and POm); 3) L3, L4, and L5 pyramidal neurons have multiple (2–4) subcellular TC innervation domains that match the dendritic compartments of pyramidal cells; and 4) a subtype of thick-tufted L5 pyramidal neurons has an additional VPM innervation domain in L4. The multiple subcellular TC innervation domains of L5 pyramidal neurons may partly explain their specific action potential patterns observed in vivo. We conclude that the substantial potential TC innervation of all excitatory neuron types in a cortical column constitutes an anatomical basis for the initial near-simultaneous representation of a sensory stimulus in different neuron types

Neocortical Axon Arbors Trade-off Material and Conduction Delay Conservation

The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons. The morphology of individual axons, therefore, defines the course of information flow within the brain. More than a century ago, Ramón y Cajal proposed that conservation laws to save material (wire) length and limit conduction delay regulate the design of individual axon arbors in cerebral cortex. Yet the spatial and temporal communication costs of single neocortical axons remain undefined. Here, using reconstructions of in vivo labelled excitatory spiny cell and inhibitory basket cell intracortical axons combined with a variety of graph optimization algorithms, we empirically investigated Cajal's conservation laws in cerebral cortex for whole three-dimensional (3D) axon arbors, to our knowledge the first study of its kind. We found intracortical axons were significantly longer than optimal. The temporal cost of cortical axons was also suboptimal though far superior to wire-minimized arbors. We discovered that cortical axon branching appears to promote a low temporal dispersion of axonal latencies and a tight relationship between cortical distance and axonal latency. In addition, inhibitory basket cell axonal latencies may occur within a much narrower temporal window than excitatory spiny cell axons, which may help boost signal detection. Thus, to optimize neuronal network communication we find that a modest excess of axonal wire is traded-off to enhance arbor temporal economy and precision. Our results offer insight into the principles of brain organization and communication in and development of grey matter, where temporal precision is a crucial prerequisite for coincidence detection, synchronization and rapid network oscillations

What’s black and white about the grey matter?

In 1873 Camillo Golgi discovered his eponymous stain, which he called la reazione nera. By adding to it the concepts of the Neuron Doctrine and the Law of Dynamic Polarisation, Santiago Ramon y Cajal was able to link the individual Golgi-stained neurons he saw down his microscope into circuits. This was revolutionary and we have all followed Cajal's winning strategy for over a century. We are now on the verge of a new revolution, which offers the prize of a far more comprehensive description of neural circuits and their operation. The hope is that we will exploit the power of computer vision algorithms and modern molecular biological techniques to acquire rapidly reconstructions of single neurons and synaptic circuits, and to control the function of selected types of neurons. Only one item is now conspicuous by its absence: the 21st century equivalent of the concepts of the Neuron Doctrine and the Law of Dynamic Polarisation. Without their equivalent we will inevitably struggle to make sense of our 21st century observations within the 19th and 20th century conceptual framework we have inherited

Cell type-specific three-dimensional structure of thalamocortical networks in a barrel column of rat vibrissal cortex

Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory−evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type− and location−specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type−specific lemniscal synaptic wiring diagram and elucidates structure−function relationships of this physiologically relevant pathway at single−cell resolutio