Thresholds for Activation of Rabbit Retinal Ganglion Cells with an Ultrafine, Extracellular Microelectrode

PURPOSE. To determine electrical thresholds required for extracellular activation of retinal ganglion cells as part of a project to develop an epiretinal prosthesis. METHODS. Retinal ganglion cells were recorded extracellularly in retinas isolated from adult New Zealand White rabbits. Electrical current pulses of 100-s duration were delivered to the inner surface of the retina from a 5-m long electrode. In about half of the cells, the point of lowest threshold was found by searching with anodal current pulses; in the other cells, cathodal current pulses were used. RESULTS. Threshold measurements were obtained near the cell bodies of 20 ganglion cells and near the axons of 19 ganglion cells. Both cathodal and anodal stimuli evoked a neural response in the ganglion cells that consisted of a single action potential of near-constant latency that persisted when retinal synaptic transmission was blocked with cadmium chloride. For cell bodies, but not axons, thresholds for both cathodal and anodal stimulation were dependent on the search method used to find the point of lowest threshold. With search and stimulation of matching polarity, cathodal stimuli evoked a ganglion cell response at lower currents (approximately one seventh to one tenth axonal threshold) than did anodal stimuli for both cell bodies and axons. With cathodal search and stimulation, cell body median thresholds were somewhat lower (approximately one half) than the axonal median thresholds. With anodal search and stimulation, cell body median thresholds were approximately the same as axonal median thresholds. CONCLUSIONS. The results suggest that cathodal stimulation should produce lower thresholds, more localized stimulation, and somewhat better selectivity for cell bodies over axons than would anodal stimulation. (Invest Ophthalmol Vis Sci. 2003; 44:3533-3543) DOI:10.1167/iovs.02-1041 O ur ultimate goal is to develop an implantable retinal prosthesis that electrically stimulates the retina to provide some functional vision to patients with advanced retinitis pigmentosa or age-related macular degeneration. Retinitis pigmentosa and age-related macular degeneration are forms of blindness that result in substantial loss of photoreceptors. Although physiological and morphologic changes may take place in the inner retinas of affected patients, 1-5 the opportunity exists for direct electrical excitation of the residual neurons as a means of restoring vision. Stimulation possibilities are either epiretinal (the stimulating points are on the inner surface of the retina) or subretinal (the stimulating points are on the outer surface of the retina, between the neural retina and the underlying pigment epithelium). The goal of the present study was to determine current threshold and increase in threshold with electrode displacement for epiretinal stimulation of retinal ganglion cells. The former can be used to judge the power requirements of a functioning prosthesis and the potential for electrochemical toxicity that occurs as current passes through the metal electrode. The latter can be used to guide the choice of interelectrode spacing and estimate the potential spatial resolution that could be derived from a prosthesis. Another motivation is the desire to achieve selective stimulation of ganglion cell bodies rather than axons en passage, which would presumably enhance the quality of perceptions induced by a retinal prosthesis. Only a few studies 6 -8 have been reported in which the currents needed to stimulate individual ganglion cells in the retina with an epiretinal electrode were investigated, and in none of these studies was the current thresholds of axons compared with cell bodies or the current thresholds measured as a function of electrode distance from the site of activation. Also, with the exception of Grumet et al., 8 relatively large microelectrodes have been used in these studies. A small microelectrode was used in the present study to enable a more precise study of threshold variation with electrode position near a cell body or axon of a ganglion cell. Preliminary portions of this work have been presented elsewhere 9 (Wyatt JL, et al. IOVS 1994;35:ARVO Abstract 593; Rizzo JF, et al. IOVS 1997;38:ARVO Abstract 182). MATERIALS AND METHODS Thirty-two adult New Zealand White rabbits (2-2.5 kg) were used in this study. All experimental procedures were in accordance with institutional guidelines and conformed to the guidelines of the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Retinal Preparation The rabbits were sedated by an intraperitoneal injection of urethane (1.6 g/kg) and then received an intravenous injection of pentobarbital sodium (20 mg/kg) for deep anesthesia. Under normal room lighting, an eye was enucleated and hemisected, and the vitreous humor was removed with gentle suction applied to the back of a Pasteur pipet. A strip (Ϸ1 ϫ 2 cm) of inferior retina and attached sclera including the optic nerve head was removed and laid flat, ganglion cell side up, on a 10°inclined platform. The retinal strip was superfused with a solution of 8.9 g/L Ames medium (Sigma-Aldrich, St. Louis, MO), 1.9 g/L NaHCO 3 , and 0.8 g/L D-glucose and saturated with 95% O 2 -5% CO 2 . The solution flowed by gravity over the surface of the retina at a rate of 1.4 to 1.7 mL/min. The temperature of the solution on the retina was maintained at 34°C to 36°C. Diffuse background light (Ϸ1 W/cm 2 at the retina) was present throughout the experiments

Development of a new model for rotator cuff pathology: the rabbit subscapularis muscle

Background and purpose The New Zealand white rabbit subscapularis tendon passes under a bony arch to insert on the lesser tubercle of the humerus in a manner analogous to the supraspinatus tendon in humans. We assessed whether this unique anatomy may provide a new animal model of the shoulder to improve our understanding of rotator cuff pathology

Curriculum Making as the Enactment of Dwelling in Places

This article uses an account of dwelling to interrogate the concept of curriculum making. Tim Ingold's use of dwelling to understand culture is productive here because of his implicit and explicit interest in intergenerational learning. His account of dwelling rests on a foundational ontological claim-that mental construction and representation are not the basis upon which we live in the world-which is very challenging for the kinds of curriculum making with which many educators are now familiar. It undermines assumptions of propositional knowledge and of the use of mental schemas to communicate and share. At the level of critique, then, dwelling destabilizes contemporary ideas of curriculum as textual, pre-specified content for transmission or pre-defined objectives or standardized activity. The positive claims of dwelling are equally challenging, for these are that the world is a domain of relational entanglement in which an organism can be no more than a point of growth for an emergent ‘environment', and meaning only inheres in these relations. The paper articulates how differentiation (of learner, salient meanings, knowledge, skill and place) are possible in such an ontology, and how curriculum making can be understood from this perspective as being the remaking of relationships between these

Remembrances of Steve Ellmann, Still Present

In Memoriam: Steven Ellman

Phenomenology As Philosophy and Method

Phenomenology is a philosophical movement that approaches the study of human beings and their culture differently from the logical positivist model used in the natural sciences and in special education. phenomenologists view the application of the logical positivist model to the study of human beings as inappropriate because the model does not address the uniqueness of human life. in this article, the theroetical assumptions and methodological orientations of phenomenology are discussed, followed by their applications to ways of doing research in special education.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68638/2/10.1177_074193259501600305.pd