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Hoffman L.,IMEC | Hoffman L.,Catholic University of Leuven | Welkenhuysen M.,IMEC | Andrei A.,IMEC | And 13 more authors.
Technical Digest - International Electron Devices Meeting, IEDM | Year: 2016

Moore s law in neural sciences: we present an optical neural probe (optoprobe) with the highest integration density of optrodes-electrodes using a CMOS process platform in 193 nm lithography. We designed, developed, and packaged an ultrathin (30 μm) optical neural probe, co-integrating silicon nitride (SixNy) photonics and biocompatible titanium nitride (TiN) electrodes (1). Functionality was verified in vivo by optically evoking and electrically recording neuronal activity in a mouse brain. Our design takes advantage of CMOS technology and incorporates 12 miniaturized optical outputs (optrodes) placed symmetrically next to 24 recording electrodes on a narrow 100-μm wide shank. We achieved an unprecedented optrode density by integrating grating couplers (GCs) instead of traditional end-butt coupling. The size of each optrode and electrode is 6 × 20 μm2 and 10 × 10 μm2 respectively, which is the typical size of a neuron. The system was capable of local excitation and recording of transduced neurons, a breakthrough achieved by the high-density integration. © 2015 IEEE. Source

Tewari D.,Indian Institute of Technology Madras | Mukhopadhyay M.,Indian Institute of Technology Madras | Nekkanti M.S.,Indian Institute of Technology Madras | Vallabhaneni S.,Indian Institute of Technology Madras | And 5 more authors.
Journal of Functional Foods | Year: 2016

Centella asiatica (CA) is commonly used as a leafy vegetable in many Asian countries. Consumption of CA is believed to prevent neuronal damage and improve brain function. The protective effect of CA on N2a cells were evaluated using ischaemia-reperfusion (IR) injury and oxygen-glucose deprivation (OGD) models in order to shed light on its molecular mechanism of action. Aqueous-methanolic extract of the CA leaves protected N2a cells against IR injury. CA reduced the levels of intracellular reactive oxygen species (ROS). It also prevented the elevation of intracellular calcium and attenuated the change of mitochondrial membrane potential, caused by OGD. When VDAC-was knocked down in N2a cells, CA failed to protect cells against IR injury. Further, CA modulated the properties of human VDAC-(hVDAC-1). hVDAC-1, when reconstituted in the lipid bilayer membrane, showed higher conductance after treating with CA. CA stabilized hVDAC-in open state, which is possibly associated with its cytoprotective effect. © 2015 Elsevier Ltd. Source

Couto J.,University of Antwerp | Couto J.,Neuroelectronics Research Flanders | Linaro D.,University of Antwerp | Linaro D.,Neuroelectronics Research Flanders | And 6 more authors.
PLoS Computational Biology | Year: 2015

Synchronous spiking during cerebellar tasks has been observed across Purkinje cells: however, little is known about the intrinsic cellular mechanisms responsible for its initiation, cessation and stability. The Phase Response Curve (PRC), a simple input-output characterization of single cells, can provide insights into individual and collective properties of neurons and networks, by quantifying the impact of an infinitesimal depolarizing current pulse on the time of occurrence of subsequent action potentials, while a neuron is firing tonically. Recently, the PRC theory applied to cerebellar Purkinje cells revealed that these behave as phase-independent integrators at low firing rates, and switch to a phase-dependent mode at high rates. Given the implications for computation and information processing in the cerebellum and the possible role of synchrony in the communication with its post-synaptic targets, we further explored the firing rate dependency of the PRC in Purkinje cells. We isolated key factors for the experimental estimation of the PRC and developed a closed-loop approach to reliably compute the PRC across diverse firing rates in the same cell. Our results show unambiguously that the PRC of individual Purkinje cells is firing rate dependent and that it smoothly transitions from phase independent integrator to a phase dependent mode. Using computational models we show that neither channel noise nor a realistic cell morphology are responsible for the rate dependent shift in the phase response curve. © 2015 Couto et al. Source

Soldano A.,Laboratory of Ion Channel Research | Soldano A.,Center for the Biology of Disease | Alpizar Y.A.,Laboratory of Ion Channel Research | Boonen B.,Laboratory of Ion Channel Research | And 13 more authors.
eLife | Year: 2016

Detecting pathogens and mounting immune responses upon infection is crucial for animal health. However, these responses come at a high metabolic price (McKean and Lazzaro, 2011, Kominsky et al., 2010), and avoiding pathogens before infection may be advantageous. The bacterial endotoxins lipopolysaccharides (LPS) are important immune system infection cues (Abbas et al., 2014), but it remains unknown whether animals possess sensory mechanisms to detect them prior to infection. Here we show that Drosophila melanogaster display strong aversive responses to LPS and that gustatory neurons expressing Gróóa bitter receptors mediate avoidance of LPS in feeding and egg laying assays. We found the expression of the chemosensory cation channel dTRPA1 in these cells to be necessary and sufficient for LPS avoidance. Furthermore, LPS stimulates Drosophila neurons in a TRPA1-dependent manner and activates exogenous dTRPA1 channels in human cells. Our findings demonstrate that flies detect bacterial endotoxins via a gustatory pathway through TRPA1 activation as conserved molecular mechanism. © Soldano et al. Source

Husken U.,University of Heidelberg | Stickney HeatherL.,University College London | Gestri G.,University College London | Bianco IsaacH.,University College London | And 27 more authors.
Current Biology | Year: 2014

Background: Although left-right asymmetries are common features of nervous systems, their developmental bases are largely unknown. In the zebrafish epithalamus, dorsal habenular neurons adopt medial (dHbm) and lateral (dHbl) subnuclear character at very different frequencies on the left and right sides. The left-sided parapineal promotes the elaboration of dHbl character in the left habenula, albeit by an unknown mechanism. Likewise, the genetic pathways acting within habenular neurons to control their asymmetric differentiated character are unknown. Results: In a forward genetic screen for mutations that result in loss of habenular asymmetry, we identified two mutant alleles of tcf7l2, a gene that encodes a transcriptional regulator of Wnt signaling. In tcf7l2 mutants, most neurons on both sides differentiate with dHbl identity. Consequently, the habenulae develop symmetrically, with both sides adopting a pronounced leftward character. Tcf7l2 acts cell automously in nascent equipotential neurons, and on the right side, it promotes dHbm and suppresses dHbl differentiation. On the left, the parapineal prevents this Tcf7l2-dependent process, thereby promoting dHbl differentiation. Conclusions: Tcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries. © 2014 The Authors. Source

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