A. M. Litke

Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration

Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type retinas between ages P37 and P752. During degeneration, retinal thickness declined by 50%, largely as a consequence of photoreceptor loss. Spontaneous electrical activity in retinal ganglion cells initially increased two- to threefold, but returned to nearly normal levels around P600. A profound decrease in the number of light-responsive ganglion cells was observed during degeneration, culminating in retinas without detectable light responses by P550. Ganglion cells from transgenic and wild-type animals were targeted for focal electrical stimulation using multielectrode arrays with electrode diameters of approximately 10 microns. Ganglion cells were stimulated directly and the success rate of stimulation in both groups was 60-70% at all ages. Surprisingly, thresholds (approximately 0.05 mC/cm(2)) and latencies (approximately 0.25 ms) in P23H rat ganglion cells were comparable to those in wild-type ganglion cells at all ages and showed no change over time. Thus ganglion cells in P23H rats respond normally to direct electrical stimulation despite severe photoreceptor degeneration and complete loss of light responses. These findings suggest that high-resolution epiretinal prosthetic devices may be effective in treating vision loss resulting from photoreceptor degeneration.

The design, construction and performance of the ALEPH silicon vertex detector

Abstract The ALEPH silicon vertex detector is the first detector operating in a colliding beam environment that uses silicon strip detectors which provide readout on both sides and hence a three-dimensional point measurement for the trajectory of charged particles. The detector system was commissioned successfully at the e+e− collider LEP at the research centre CERN, Switzerland, during the year 1991 while taking data at the Z0 resonance. The achieved spatial resolution of the complete 73 728 channel device (intrinsic plus alignment) is 12 μm in the r-f view and 12 μm in the z view. The design and construction of the entire detector system are discussed in detail and the experience gained in running the detector will be described with special emphasis on the uses of this novel tracking device for the physics of short-lived heavy particles produced in the decays of the Z0 resonance.

Recent results and running experience of the new ALEPH Vertex Detector

A description of the new ALEPH Vertex Detectors (VEDET 91), including the new mechanical structure and the improved data acquisition system, is given. The apparatus consists of two complete layers of silicon detectors with double-sided readout which provide full x,y,z information on the impact points of charge particles. The authors present results on signal-to-noise ratio for minimum ionizing particles and efficiency in hit/track matching. Results on position, impact parameter, and momentum resolution are also shown as measured using high-momentum muons. Preliminary results on single hit and impact parameter resolution show that the detectors and VLSI read-out electronics work as expected, and the performance compares well with previous test beam results and Monte Carlo simulations. Preliminary results on precision vertex reconstruction show a significant improvement in the data analysis which will be fully exploited in studying tau , b and c physics when all statistics are available.<<ETX>>

Inclusive production of D-mesons in e+e− annihilation at 7 GeV☆

Abstract Inclusive momentum and energy spectra of neutral and charged D-mesons produced in e+e− annihilation at energies near 7 GeV are presented. The slope of the energy spectrum is similar to the charged pion spectrum at the same energy. The inclusive cross section σ(e+e−→ D or D + anything) at 7 GeV is 4.8±1.3 nb.

Inclusive

We have measured inclusive ..gamma.. and ..pi../sup 0/ production in multiprong events produced by e/sup +/e/sup -/ annihilation in the center-of-mass energy range 4.9 to 7.4 GeV. We find that ..pi../sup 0/ inclusive cross section to be consistent in shape and normalization with half the charged-..pi.. cross section between chi = 0.15 and 0.60, with an integrated inclusive cross-section ratio of sigma (..pi../sup 0/)/ vertical-bar (sigma (..pi../sup +/) + sigma (..pi../sup -/) vertical-bar = 0.47 +- 0.10.

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Two multichannel Application Specific Integrated Circuits (ASICs) for extracellular recording of neuronal signals from live retinal tissues using microelectrode arrays have been developed. In this paper we discuss the requirements concerning the IC parameters and characteristics as well as present the designs and the test results. The required electronic functionality has been divided into two ASICs: PLAT-64 and NEURO-64 realized in a 0.7 /spl mu/m CMOS process. The PLAT-64 chip comprises 64 capacitors of 150 pF each, and 64 addressable and controlled DC current sources for platinization of electrodes. The NEURO-64 chip comprises 64 channels of low noise amplifiers and bandpass filters and an analog multiplexer. The low noise performance of the preamplifier has been achieved by careful selection of a CMOS process and by proper sizing and biasing of the input devices. The required lower cut-off frequency of 20 Hz has been obtained by employing a novel RC filter structure.

and

Abstract A large system of silicon strip detectors with double sided readout has been successfully commissioned over the course of the last year at the e + e − collider LEP. The readout of this 73 728 channel system is performed with custom designed VLSI charge sensitive amplifier chips (CAMEX64A). An overall point resolution of 12 μm on both sides has been acheived for the complete system. The most important difficulties during the run were beam losses into the detector, and a chemical agent deposited onto the electronics; however, the damage from these sources was understood and brought under control. This and other results of the 1991 data-taking run are described with special emphasis on the operational experience.

\pi^0

Understanding how the retina encodes the visual scene is a problem, which requires large area, high-density microelectrode arrays to solve. The correlated signals that emerge from the output (ganglion) cells of the retina form a code, which is not well understood. We use a combination of electron beam lithography, photolithography and dry-etch pattern transfer to realise a 519-electrode array in the transparent conductor indium tin oxide (ITO). The electrodes are spaced at 60 µm in a hexagonal close-packed geometry. A mix and match lithography procedure is utilised, whereby the high-density inner region is fabricated using electron beam lithography whilst the outer sections are realised by photolithography. Reactive ion etching (RIE), using CH4/H2, of the ITO forms the array structure and SF6 RIE allows resist removal and patterning of vias through a plasma deposited Si3N4 protective layer. The electrical properties of the ITO layer are unaffected by the etching procedures, A reliable method for achieving low-impedance electroplated platinum electrodes has been employed to yield electrode impedances of ∼ 20 kΩ. An array fabricated using these dry-etch techniques is shown to record action potentials from live retinal tissue in neurophysiological experiments.

Production in

The development of high-density, multi-channel circuitry for the detection of low-level signals in particle physics has potential application in other areas of science. Here we use this technology to study biological neural networks. For example understanding the code that the retina uses to process visual images is of great interest. To this end we have fabricated a 61-channel microelectrode array on the transparent conductor indium tin oxide. We analyse the effect of contact size on electrode characteristics and demonstrate the performance of these arrays in neurophysiological experiments using retinal tissue. We present some preliminary results in the development of 519 channel arrays to allow an increased area of the retina to be studied.

e^+ e^-

We have measured inclusive ..gamma.. and ..pi../sup 0/ production in multiprong events produced by e/sup +/e/sup -/ annihilation in the center-of-mass energy range 4.9 to 7.4 GeV. We find that ..pi../sup 0/ inclusive cross section to be consistent in shape and normalization with half the charged-..pi.. cross section between chi = 0.15 and 0.60, with an integrated inclusive cross-section ratio of sigma (..pi../sup 0/)/ vertical-bar (sigma (..pi../sup +/) + sigma (..pi../sup -/) vertical-bar = 0.47 +- 0.10.