Chethan Pandarinath

Structural, microstructural, and electrical properties of gold films and Schottky contacts on remote plasma-cleaned, n -type ZnO{0001} surfaces

Current–voltage measurements of Au contacts deposited on ex situ cleaned, n-type ZnO(0001) [(0001¯)] surfaces showed reverse bias leakage current densities of ∼0.01(∼0.1)A∕cm2 at 4.6 (3.75) V reverse bias and ideality factors >2 (both surfaces) before sharp, permanent breakdown (soft breakdown). This behavior was due primarily to the presence of (1.6–2.0)±0.1[(0.7–2.6)±0.1] monolayers (ML) of hydroxide, which forms an electron accumulation layer and increases the surface conductivity. In situ remote plasma cleaning of the (0001) [(0001¯)] surfaces using a 20vol%O2∕80vol%He mixture for the optimized temperatures, times, and pressure of 550±20°C(525±20°C), 60 (30) min, and 0.050 Torr reduced the thickness of the hydroxide layer to ∼0.4±0.1ML and completely eliminated all detectable hydrocarbon contamination. Subsequent cooling of both surfaces in the plasma ambient resulted in the chemisorption of oxygen and a change from 0.2 eV of downward band bending for samples cooled in vacuum to 0.3 eV of upward band ...

Retinal prosthetic strategy with the capacity to restore normal vision

Retinal prosthetics offer hope for patients with retinal degenerative diseases. There are 20–25 million people worldwide who are blind or facing blindness due to these diseases, and they have few treatment options. Drug therapies are able to help a small fraction of the population, but for the vast majority, their best hope is through prosthetic devices [reviewed in Chader et al. (2009) Prog Brain Res 175:317–332]. Current prosthetics, however, are still very limited in the vision that they provide: for example, they allow for perception of spots of light and high-contrast edges, but not natural images. Efforts to improve prosthetic capabilities have focused largely on increasing the resolution of the device’s stimulators (either electrodes or optogenetic transducers). Here, we show that a second factor is also critical: driving the stimulators with the retina’s neural code. Using the mouse as a model system, we generated a prosthetic system that incorporates the code. This dramatically increased the system’s capabilities—well beyond what can be achieved just by increasing resolution. Furthermore, the results show, using 9,800 optogenetically stimulated ganglion cell responses, that the combined effect of using the code and high-resolution stimulation is able to bring prosthetic capabilities into the realm of normal image representation.

Clinical translation of a high-performance neural prosthesis

Neural prostheses have the potential to improve the quality of life of individuals with paralysis by directly mapping neural activity to limb- and computer-control signals. We translated a neural prosthetic system previously developed in animal model studies for use by two individuals with amyotrophic lateral sclerosis who had intracortical microelectrode arrays placed in motor cortex. Measured more than 1 year after implant, the neural cursor-control system showed the highest published performance achieved by a person to date, more than double that of previous pilot clinical trial participants.

Virtual typing by people with tetraplegia using a self-calibrating intracortical brain-computer interface

Individuals with tetraplegia are able to type self-paced for hours across multiple days using a self-calibrating point-and-click intracortical brain-computer interface. Prolonged typing with refined BCI The fact that the brain can be hooked up to a computer to allow paralyzed individuals to type is already a technological feat. But, these so-called brain-computer interface technologies can be tiring and burdensome for users, requiring frequent disruptions for recalibration when the decoded neural signals change. Jarosiewicz and colleagues therefore combined three calibration methods—retrospective target interference, velocity bias correction, and adaptive tracking of neural features—for seamless typing and stable neural control. This combination allowed two individuals with tetraplegia and with cortical microelectrode arrays to compose long texts at their own paces, with no need to interrupt typing for recalibration. Brain-computer interfaces (BCIs) promise to restore independence for people with severe motor disabilities by translating decoded neural activity directly into the control of a computer. However, recorded neural signals are not stationary (that is, can change over time), degrading the quality of decoding. Requiring users to pause what they are doing whenever signals change to perform decoder recalibration routines is time-consuming and impractical for everyday use of BCIs. We demonstrate that signal nonstationarity in an intracortical BCI can be mitigated automatically in software, enabling long periods (hours to days) of self-paced point-and-click typing by people with tetraplegia, without degradation in neural control. Three key innovations were included in our approach: tracking the statistics of the neural activity during self-timed pauses in neural control, velocity bias correction during neural control, and periodically recalibrating the decoder using data acquired during typing by mapping neural activity to movement intentions that are inferred retrospectively based on the user’s self-selected targets. These methods, which can be extended to a variety of neurally controlled applications, advance the potential for intracortical BCIs to help restore independent communication and assistive device control for people with paralysis.

Ganglion Cell Adaptability: Does the Coupling of Horizontal Cells Play a Role?

Background The visual system can adjust itself to different visual environments. One of the most well known examples of this is the shift in spatial tuning that occurs in retinal ganglion cells with the change from night to day vision. This shift is thought to be produced by a change in the ganglion cell receptive field surround, mediated by a decrease in the coupling of horizontal cells. Methodology/Principal Findings To test this hypothesis, we used a transgenic mouse line, a connexin57-deficient line, in which horizontal cell coupling was abolished. Measurements, both at the ganglion cell level and the level of behavioral performance, showed no differences between wild-type retinas and retinas with decoupled horizontal cells from connexin57-deficient mice. Conclusion/Significance This analysis showed that the coupling and uncoupling of horizontal cells does not play a dominant role in spatial tuning and its adjustability to night and day light conditions. Instead, our data suggest that another mechanism, likely arising in the inner retina, must be responsible.

Symmetry Breakdown in the ON and OFF Pathways of the Retina at Night: Functional Implications

Several recent studies have shown that the ON and OFF channels of the visual system are not simple mirror images of each other, that their response characteristics are asymmetric (Chichilnisky and Kalmar, 2002; Sagdullaev and McCall, 2005). How the asymmetries bear on visual processing is not well understood. Here, we show that ON and OFF ganglion cells show a strong asymmetry in their temporal adaptation to photopic (day) and scotopic (night) conditions and that the asymmetry confers a functional advantage. Under photopic conditions, the ON and OFF ganglion cells show similar temporal characteristics. Under scotopic conditions, the two cell classes diverge—ON cells shift their tuning to low temporal frequencies, whereas OFF cells continue to respond to high. This difference in processing corresponds to an asymmetry in the natural world, one produced by the Poisson nature of photon capture and persists over a broad range of light levels. This work characterizes a previously unknown divergence in the ON and OFF pathways and its utility to visual processing. Furthermore, the results have implications for downstream circuitry and thus offer new constraints for models of downstream processing, since ganglion cells serve as building blocks for circuits in higher brain areas. For example, if simple cells in visual cortex rely on complementary interactions between the two pathways, such as push–pull interactions (Alonso et al., 2001; Hirsch, 2003), their receptive fields may be radically different under scotopic conditions, when the ON and OFF pathways are out of sync.

Recruitment of PfSET2 by RNA polymerase II to variant antigen encoding loci contributes to antigenic variation in P. falciparum.

Histone modifications are important regulators of gene expression in all eukaryotes. In Plasmodium falciparum, these epigenetic marks regulate expression of genes involved in several aspects of host-parasite interactions, including antigenic variation. While the identities and genomic positions of many histone modifications have now been cataloged, how they are targeted to defined genomic regions remains poorly understood. For example, how variant antigen encoding loci (var) are targeted for deposition of unique histone marks is a mystery that continues to perplex the field. Here we describe the recruitment of an ortholog of the histone modifier SET2 to var genes through direct interactions with the C-terminal domain (CTD) of RNA polymerase II. In higher eukaryotes, SET2 is a histone methyltransferase recruited by RNA pol II during mRNA transcription; however, the ortholog in P. falciparum (PfSET2) has an atypical architecture and its role in regulating transcription is unknown. Here we show that PfSET2 binds to the unphosphorylated form of the CTD, a property inconsistent with its recruitment during mRNA synthesis. Further, we show that H3K36me3, the epigenetic mark deposited by PfSET2, is enriched at both active and silent var gene loci, providing additional evidence that its recruitment is not associated with mRNA production. Over-expression of a dominant negative form of PfSET2 designed to disrupt binding to RNA pol II induced rapid var gene expression switching, confirming both the importance of PfSET2 in var gene regulation and a role for RNA pol II in its recruitment. RNA pol II is known to transcribe non-coding RNAs from both active and silent var genes, providing a possible mechanism by which it could recruit PfSET2 to var loci. This work unifies previous reports of histone modifications, the production of ncRNAs, and the promoter activity of var introns into a mechanism that contributes to antigenic variation by malaria parasites.

High performance communication by people with paralysis using an intracortical brain-computer interface

Brain-computer interfaces (BCIs) have the potential to restore communication for people with tetraplegia and anarthria by translating neural activity into control signals for assistive communication devices. While previous pre-clinical and clinical studies have demonstrated promising proofs-of-concept (Serruya et al., 2002; Simeral et al., 2011; Bacher et al., 2015; Nuyujukian et al., 2015; Aflalo et al., 2015; Gilja et al., 2015; Jarosiewicz et al., 2015; Wolpaw et al., 1998; Hwang et al., 2012; Spüler et al., 2012; Leuthardt et al., 2004; Taylor et al., 2002; Schalk et al., 2008; Moran, 2010; Brunner et al., 2011; Wang et al., 2013; Townsend and Platsko, 2016; Vansteensel et al., 2016; Nuyujukian et al., 2016; Carmena et al., 2003; Musallam et al., 2004; Santhanam et al., 2006; Hochberg et al., 2006; Ganguly et al., 2011; O’Doherty et al., 2011; Gilja et al., 2012), the performance of human clinical BCI systems is not yet high enough to support widespread adoption by people with physical limitations of speech. Here we report a high-performance intracortical BCI (iBCI) for communication, which was tested by three clinical trial participants with paralysis. The system leveraged advances in decoder design developed in prior pre-clinical and clinical studies (Gilja et al., 2015; Kao et al., 2016; Gilja et al., 2012). For all three participants, performance exceeded previous iBCIs (Bacher et al., 2015; Jarosiewicz et al., 2015) as measured by typing rate (by a factor of 1.4–4.2) and information throughput (by a factor of 2.2–4.0). This high level of performance demonstrates the potential utility of iBCIs as powerful assistive communication devices for people with limited motor function. Clinical Trial No: NCT00912041 DOI: http://dx.doi.org/10.7554/eLife.18554.001

A Novel Mechanism for Switching a Neural System from One State to Another

An animals ability to rapidly adjust to new conditions is essential to its survival. The nervous system, then, must be built with the flexibility to adjust, or shift, its processing capabilities on the fly. To understand how this flexibility comes about, we tracked a well-known behavioral shift, a visual integration shift, down to its underlying circuitry, and found that it is produced by a novel mechanism – a change in gap junction coupling that can turn a cell class on and off. The results showed that the turning on and off of a cell class shifted the circuits behavior from one state to another, and, likewise, the animals behavior. The widespread presence of similar gap junction-coupled networks in the brain suggests that this mechanism may underlie other behavioral shifts as well.

Neural population dynamics in human motor cortex during movements in people with ALS

The prevailing view of motor cortex holds that motor cortical neural activity represents muscle or movement parameters. However, recent studies in non-human primates have shown that neural activity does not simply represent muscle or movement parameters; instead, its temporal structure is well-described by a dynamical system where activity during movement evolves lawfully from an initial pre-movement state. In this study, we analyze neuronal ensemble activity in motor cortex in two clinical trial participants diagnosed with Amyotrophic Lateral Sclerosis (ALS). We find that activity in human motor cortex has similar dynamical structure to that of non-human primates, indicating that human motor cortex contains a similar underlying dynamical system for movement generation. Clinical trial registration: NCT00912041. DOI: http://dx.doi.org/10.7554/eLife.07436.001