Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex

Autologous Serum Eye Drops for Post-Chemical Injuries and Corneal Epithelial Defects

Aim: To evaluate success rate (efficacy, safety) in treatment of post-chemical injuries and corneal defects using autologous serum eye drops.Material and Methods: Authors reviewed 93 patients (116 eyes) hospitalized in Clinic of ophthalmology from 2010 to 2013, who had post-causoma corneal defects that were nonresponsive to conventional treatment and were treated with serum therapy. Authors correlated time of epithelialization of defects with rate of epithelial healing.Results: Authors investigated 93 patients (52 males, 41 females; aged 18 - 74) for treatment of corneal defects. Application of autologous serum therapy 56 (48.28%) of 116 eyes was healed in an average time of 4 weeks. Among 116 eyes, epithelial defects healed in 4 (3.45%) within 1 week, in additional 17 (14.65%) in 1-2 weeks, totalling 31 (26.72%) within 3 weeks. Five eyes (4.31%) completely healed at 5 week; three eyes (2.59%) had subsequent healing of epithelial defect at 6 week; 56 eyes completely healed within one month, and the remaining eight eyes healed within 1.5 month.Conclusion: Using serum therapy, it was managed to reduce time of healing from eleven weeks, which were necessary just couple years ago (before 2010) to four (maximum six) weeks to complete healing which are necessary today

A Versatile and Open-Source Rapid LED Switching System for One-Photon Imaging and Photo-Activation

Combining fluorescence and transmitted light sources for microscopy is an invaluable method in cellular neuroscience to probe the molecular and cellular mechanisms of cells. This approach enables the targeted recording from fluorescent reporter protein expressing neurons or glial cells in brain slices and fluorescence-assisted electrophysiological recordings from subcellular structures. However, the existing tools to mix multiple light sources in one-photon microscopy are limited. Here, we present the development of several microcontroller devices that provide temporal and intensity control of light emitting diodes (LEDs) for computer controlled microscopy illumination. We interfaced one microcontroller with μManager for rapid and dynamic overlay of transmitted and fluorescent images. Moreover, on the basis of this illumination system we implemented an electronic circuit to combine two pulsed LED light sources for fast (up to 1 kHz) ratiometric calcium (Ca2+) imaging. This microcontroller enabled the calibration of intracellular Ca2+ concentration and furthermore the combination of Ca2+ imaging with optogenetic activation. The devices are based on affordable components and open-source hardware and software. Integration into existing bright-field microscope systems will take ∼1 day. The microcontroller based LED imaging substantially advances conventional illumination methods by limiting light exposure and adding versatility and speed

Weak-Singlet Fermions: Models and Constraints

We employ data from precision electroweak tests and collider searches to derive constraints on the possibility that weak-singlet fermions mix with the ordinary Standard Model fermions. Our findings are presented within the context of a theory with weak-singlet partners for all ordinary fermions and theories in which only third-generation fermions mix with weak singlets. In addition, we indicate how certain results can be applied more widely in theories containing exotic fermions.Comment: 29 pages, 12 figures; added 1 reference, expanded introductio

A Heavy Top Quark From Flavor-Universal Colorons

Ordinary technicolor and extended technicolor cannot produce the heavy top quark unaided. We demonstrate that a flavor-universal extension of the color interactions combined with an extended hypercharge sector that singles out the third generation can provide the necessary assistance. We discuss current experimental constraints and suggest how collider experiments can search for the predicted new heavy gauge bosons.Comment: 14 pages, 3 figures, LaTeX, updated reference, fixed typ

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)