Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain

Individuals with Down syndrome (DS) exhibit Alzheimer’s disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS contains p-Tau at an early age. The goal of the study was to investigate whether NDEVs isolated from the blood of individuals with DS can spread Tau pathology in the brain of wildtype mice. We purified NDEVs from the plasma of patients with DS-AD and controls and injected small quantities using stereotaxic surgery into the dorsal hippocampus of adult wildtype mice. Seeding competent Tau conformers were amplified in vitro from DS-AD NDEVs but not NDEVs from controls. One month or 4 months post-injection, we examined Tau pathology in mouse brains. We found abundant p-Tau immunostaining in the hippocampus of the mice injected with DS-AD NDEVs compared to injections of age-matched control NDEVs. Double labeling with neuronal and glial markers showed that p-Tau staining was largely found in neurons and, to a lesser extent, in glial cells and that p-Tau immunostaining was spreading along the corpus callosum and the medio-lateral axis of the hippocampus. These studies demonstrate that NDEVs from DS-AD patients exhibit Tau seeding capacity and give rise to tangle-like intracellular inclusions.

Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation

The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of Caenorhabditis elegans motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the C. elegans sensorimotor system. C. elegans exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems. C. elegans has manifested itself as a compact model to search for general principles of sensorimotor behaviours. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

Recording High Frequency Neural Signals Using Conformable and Low-Impedance ECoG Electrodes Arrays Coated with PEDOT-PSS-PEG

Electrocorticography (ECoG) is receiving growing attention for both clinical and research applications thanks to its reduced invasiveness and ability of addressing large cortical areas. These benefits come with a main drawback, i.e. a limited frequency bandwidth. However, recent studies have shown that spiking activity from cortical neurons can be recorded when the ECoG grids present the following combined properties: (I) conformable substrate, (II) small neuron-sized electrodes with (III) low-impedance interfaces. We introduce here an ad-hoc designed ECoG device for investigating how electrode size, interface material composition and electrochemical properties affect the capability to record evoked and spontaneous neural signals from the rat somatosensory cortex and influence the ability to record high frequency neural signal components.Contact diameter reduction down to 8 μm was possible thanks to a specific coating of a (3,4-ethylenedioxytiophene)-poly (styrenesulfonate)-poly-(ethyleneglycol) (PEDOT-PSS-PEG) composite that drastically reduces impedance and increases electrical and ionic conductivities. In addition, the extreme thinness of the polyimide substrate (6 - 8 μm) and the presence of multiple perforations through the device ensure an effective contact with the brain surface and the free flow of cerebrospinal fluid. In-vivo validation was performed on rat somatosensory cortex.

FITC-Functionalized TiO2 Nanoparticles for Simultaneous Neuron Imaging and in Cell Photocatalysis

ABSTRACTCrystalline TiO2 nanoparticles were produced by scalable flame spray pyrolysis of organometallic solutions. A protocol is presented for the optimized functionalization of these particles with fluorescein isothiocyanate (FITC), an important biomedical dye via a lysine linker. The pH, stoichiometry and time for lysine reaction were determined for highest dye loading and minimized degree of polylysine formation. Acidic reaction conditions, low lysine concentration and short reaction times were found to meet this aim. The resulting particles were used for imaging single neurons, showing high fluorescence emission and ability for the particles to diffuse into small neuron structures such as dendrites.

The sizes of motoneurons supplying hindlimb muscles in the mouse

Motoneurons supplying identified muscle groups in the mouse spinal cord were labelled by retrograde transport of horseradish peroxidase. The size of motoneurons was estimated by measuring perimeter and cross-sectional area at the level of the nucleolus for the following seven major muscle groups: quadriceps femoris, adductors and gracilis, gluteal musculature, hamstring muscles, posterior crural musculature, anterolateral crural musculature and intrinsic musculature of the foot. The qualitative observation of two size ranges of motoneuron was supported by the measurements. Frequency distribution histograms of motoneuronal cross sectional area were bimodal for all motoneuronal groups except for the foot musculature. The population parameters and proportions for the six bimodal histograms were estimated by the method of maximum likelihood. It was found that the mean area of the small neuron component, which were presumed to be gamma motoneurons, was similar for the six bimodal systems. In contrast to this the mean area of the large neuron component, presumed to be alpha motoneurons, was found to be different for the six bimodal systems; motoneurons supplying more proximal muscles showed a larger mean area than those supplying distal muscles. The mean area of both components was unaffected by survival time and this was interpreted as indicating that changes in survival time did not label greater numbers of small or large motoneurons. The proportion of motoneurons in the small neuron component was found to vary from 9 to 27%.